Obesity

My 50th medical school reunion has come and gone. This milestone offered me another opportunity to look back over the last 5 decades of pediatrics that I have watched pass under the bridge. Triggered by the discovery of two recently published studies, this particular view back over my shoulder induced a wave of sadness, anger, and frustration that I have had trouble shaking.

The first study demonstrated a strong positive effect of exercise on academic achievement, the other found that children who were more physically active have weathered the pandemic with fewer mental health problems.

These studies are just two pieces of a growing body of evidence that our sedentary lifestyles are shortening our lives and launching our children into adulthood burdened with a raft of health risks they could possibly have avoided by being more physically active. Encountering these two papers just as the alumni office was inviting me to engage in an orgy of retrospection and introspection made me consider how little I and others in my profession have done to substantially address this scourge on our young people.

Yes, I have tried to encourage my patients to be less sedentary and more active. Yes, I have tried to set a very visible example by bicycling and walking around town. Yes, I have coached youth sports teams. All of my children and grandchildren are leading active lives and appear to be reaping the benefits. But in the grander scheme of things I feel that neither I nor the American Academy of Pediatrics has made a difference.

In March of 2020 the AAP published a clinical report that lists the numerous positive associations between activity and health that includes a comprehensive collection of suggestions for providers on how we might assess the problem of inactivity and then play a role in addressing it with our patients and our communities. Unfortunately, the message’s importance was lost in the glut of pandemic news.

While the AAP’s report should have been published many decades ago, I doubt the delay lessened its impact significantly because the report is primarily a compendium of recommendations that in the long run will be seen as just another example of us believers preaching to the choir.

Making lifestyle changes on the order of magnitude necessary to convert an increasingly sedentary population into one that unconsciously becomes physically active requires more than recommendations. It is only natural that folks have trouble saying “No.”

No to the entertainment of electronic devices. No to the comforts of all-weather enclosed transportation. No to hours on the couch. Overcoming the inertia built into our society is going to require more than encouragement, recommendations, and professional sports–sponsored presidential initiatives.

Mandate has become a politically charged dirty word. But our current experience with the COVID-19 vaccines should help us realize that there is a significant segment of the population that doesn’t like being told what to do even if the outcome is in their best interest. Education and rewards have fallen short, but the evidence is mounting that mandates can work.

There was a time when physical activity was built into every child’s school day. For a variety of bad reasons, vigorous physical education classes and once- or twice-daily outdoor recesses have disappeared from the educational landscape. It is time to return to them in a robust form. Unfortunately, because activity isn’t happening at home it will take a government mandate.

There will be pushback. Even from some educators whose observations should have shown them the critical role of physical activity in health and academic success. We must move the distraction of the phenomenon once known simply as hyperactivity to the back burner and tackle the real epidemic of hypoactivity that is destroying our children.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

My 50th medical school reunion has come and gone. This milestone offered me another opportunity to look back over the last 5 decades of pediatrics that I have watched pass under the bridge. Triggered by the discovery of two recently published studies, this particular view back over my shoulder induced a wave of sadness, anger, and frustration that I have had trouble shaking.

The first study demonstrated a strong positive effect of exercise on academic achievement, the other found that children who were more physically active have weathered the pandemic with fewer mental health problems.

These studies are just two pieces of a growing body of evidence that our sedentary lifestyles are shortening our lives and launching our children into adulthood burdened with a raft of health risks they could possibly have avoided by being more physically active. Encountering these two papers just as the alumni office was inviting me to engage in an orgy of retrospection and introspection made me consider how little I and others in my profession have done to substantially address this scourge on our young people.

Yes, I have tried to encourage my patients to be less sedentary and more active. Yes, I have tried to set a very visible example by bicycling and walking around town. Yes, I have coached youth sports teams. All of my children and grandchildren are leading active lives and appear to be reaping the benefits. But in the grander scheme of things I feel that neither I nor the American Academy of Pediatrics has made a difference.

In March of 2020 the AAP published a clinical report that lists the numerous positive associations between activity and health that includes a comprehensive collection of suggestions for providers on how we might assess the problem of inactivity and then play a role in addressing it with our patients and our communities. Unfortunately, the message’s importance was lost in the glut of pandemic news.

While the AAP’s report should have been published many decades ago, I doubt the delay lessened its impact significantly because the report is primarily a compendium of recommendations that in the long run will be seen as just another example of us believers preaching to the choir.

Making lifestyle changes on the order of magnitude necessary to convert an increasingly sedentary population into one that unconsciously becomes physically active requires more than recommendations. It is only natural that folks have trouble saying “No.”

No to the entertainment of electronic devices. No to the comforts of all-weather enclosed transportation. No to hours on the couch. Overcoming the inertia built into our society is going to require more than encouragement, recommendations, and professional sports–sponsored presidential initiatives.

Mandate has become a politically charged dirty word. But our current experience with the COVID-19 vaccines should help us realize that there is a significant segment of the population that doesn’t like being told what to do even if the outcome is in their best interest. Education and rewards have fallen short, but the evidence is mounting that mandates can work.

There was a time when physical activity was built into every child’s school day. For a variety of bad reasons, vigorous physical education classes and once- or twice-daily outdoor recesses have disappeared from the educational landscape. It is time to return to them in a robust form. Unfortunately, because activity isn’t happening at home it will take a government mandate.

There will be pushback. Even from some educators whose observations should have shown them the critical role of physical activity in health and academic success. We must move the distraction of the phenomenon once known simply as hyperactivity to the back burner and tackle the real epidemic of hypoactivity that is destroying our children.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

My 50th medical school reunion has come and gone. This milestone offered me another opportunity to look back over the last 5 decades of pediatrics that I have watched pass under the bridge. Triggered by the discovery of two recently published studies, this particular view back over my shoulder induced a wave of sadness, anger, and frustration that I have had trouble shaking.

The first study demonstrated a strong positive effect of exercise on academic achievement, the other found that children who were more physically active have weathered the pandemic with fewer mental health problems.

These studies are just two pieces of a growing body of evidence that our sedentary lifestyles are shortening our lives and launching our children into adulthood burdened with a raft of health risks they could possibly have avoided by being more physically active. Encountering these two papers just as the alumni office was inviting me to engage in an orgy of retrospection and introspection made me consider how little I and others in my profession have done to substantially address this scourge on our young people.

Yes, I have tried to encourage my patients to be less sedentary and more active. Yes, I have tried to set a very visible example by bicycling and walking around town. Yes, I have coached youth sports teams. All of my children and grandchildren are leading active lives and appear to be reaping the benefits. But in the grander scheme of things I feel that neither I nor the American Academy of Pediatrics has made a difference.

In March of 2020 the AAP published a clinical report that lists the numerous positive associations between activity and health that includes a comprehensive collection of suggestions for providers on how we might assess the problem of inactivity and then play a role in addressing it with our patients and our communities. Unfortunately, the message’s importance was lost in the glut of pandemic news.

While the AAP’s report should have been published many decades ago, I doubt the delay lessened its impact significantly because the report is primarily a compendium of recommendations that in the long run will be seen as just another example of us believers preaching to the choir.

Making lifestyle changes on the order of magnitude necessary to convert an increasingly sedentary population into one that unconsciously becomes physically active requires more than recommendations. It is only natural that folks have trouble saying “No.”

No to the entertainment of electronic devices. No to the comforts of all-weather enclosed transportation. No to hours on the couch. Overcoming the inertia built into our society is going to require more than encouragement, recommendations, and professional sports–sponsored presidential initiatives.

Mandate has become a politically charged dirty word. But our current experience with the COVID-19 vaccines should help us realize that there is a significant segment of the population that doesn’t like being told what to do even if the outcome is in their best interest. Education and rewards have fallen short, but the evidence is mounting that mandates can work.

There was a time when physical activity was built into every child’s school day. For a variety of bad reasons, vigorous physical education classes and once- or twice-daily outdoor recesses have disappeared from the educational landscape. It is time to return to them in a robust form. Unfortunately, because activity isn’t happening at home it will take a government mandate.

There will be pushback. Even from some educators whose observations should have shown them the critical role of physical activity in health and academic success. We must move the distraction of the phenomenon once known simply as hyperactivity to the back burner and tackle the real epidemic of hypoactivity that is destroying our children.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

The more fast food restaurants a person lives near in the United States, the more likely they are to develop type 2 diabetes, new research indicates.  

The national study of more than 4 million U.S. veterans also found the opposite association with supermarkets in suburban and rural communities but not others.

“Neighborhood food environment was associated with type 2 diabetes risk among U.S. veterans in multiple community types, suggesting potential avenues for action to address the burden of type 2 diabetes,” say Rania Kanchi, MPH, of the department of population health, New York University Langone Health, and colleagues.

Restriction of fast food establishments could benefit all types of communities, while interventions to increase supermarket availability could help minimize diabetes risk in suburban and rural communities, they stress.

“These actions, combined with increasing awareness of the risk of type 2 diabetes and the importance of healthy diet intake, might be associated with a decrease in the burden of type 2 diabetes among adults in the U.S.,” the researchers add.

The data were published online Oct. 29 in JAMA Network Open.

“The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents,” commented Lorna Thorpe, PhD, MPH, professor in the department of population health at NYU Langone and senior author of the study in a press release.

In an accompanying editorial, Elham Hatef, MD, MPH, of the Center for Population Health IT at Johns Hopkins Bloomberg School of Public Health, Baltimore, calls the study “a great example of the capabilities of [health information technology] to provide a comprehensive assessment of a person’s health, which goes beyond just documenting clinical diseases and medical interventions.”
 

Research has large geographic breadth

The study is notable for its large geographic breadth, say the researchers.

“Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas,” Ms. Kanchi said in the press statement.

“Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not,” Ms. Kanchi continued.

The research included data for 4,100,650 individuals from the Veterans Affairs electronic health records (EHRs) who didn’t have type 2 diabetes at baseline, between 2008 and 2016. After a median follow-up of 5.5 person-years, 13.2% developed type 2 diabetes. Cumulative incidence was greater among those who were older, those who were non-Hispanic Black compared with other races, and those with disabilities and lower incomes.

The proportion of adults with type 2 diabetes was highest among those living in high-density urban communities (14.3%), followed by low-density urban (13.1%), rural (13.2%), and suburban (12.6%) communities.

Overall, a 10% increase in the number of fast food restaurants compared with other food establishments in a given neighborhood was associated with a 1% increased risk for incident type 2 diabetes in high-density urban, low-density urban, and rural communities and a 2% increased risk in suburban communities.

In contrast, a 10% increase in supermarket density compared with other food stores was associated with a lower risk for type 2 diabetes in suburban and rural communities, but the association wasn’t significant elsewhere.

“Taken together, our findings suggest that policies specific to fast food restaurants, such as [those] ... restricting the siting of fast food restaurants and healthy beverage default laws, may be effective in reducing type 2 diabetes risk in all community types,” say the authors.

“In urban areas where population and retail density are growing, it will be even more important to focus on these policies,” they emphasize.
 

Great example of capabilities of health information technology

In the editorial, Dr. Hatef notes that methodological advances, such as natural language processing and machine learning, have enabled health systems to use real-world data such as the free-text notes in the EHR to identify patient-level risk factors for diseases or disease complications.

Such methods could be further used to “evaluate the associations between social needs and place-based [social determinants of health] and type 2 diabetes incidence and management,” Dr. Hatef adds.

And linkage of data from the EHR to such community-level data “would help to comprehensively assess and identify patients likely to experience type 2 diabetes and its complications as a result of their risk factors or characteristics of the neighborhoods where they reside.”

“This approach could foster collaborations between the health systems and at-risk communities they serve and help to reallocate health system resources to those in most need in the community to reduce the burden of type 2 diabetes and other chronic conditions among racial minority groups and socioeconomically disadvantaged patients and to advance population health.”

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the Commonwealth Universal Research Enhancement program funded by the Pennsylvania Department of Health, the Urban Health Collaborative at Drexel University, and the Built Environment and Health Research Group at Columbia University. Ms. Kanchi and Dr. Hatef have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The more fast food restaurants a person lives near in the United States, the more likely they are to develop type 2 diabetes, new research indicates.  

The national study of more than 4 million U.S. veterans also found the opposite association with supermarkets in suburban and rural communities but not others.

“Neighborhood food environment was associated with type 2 diabetes risk among U.S. veterans in multiple community types, suggesting potential avenues for action to address the burden of type 2 diabetes,” say Rania Kanchi, MPH, of the department of population health, New York University Langone Health, and colleagues.

Restriction of fast food establishments could benefit all types of communities, while interventions to increase supermarket availability could help minimize diabetes risk in suburban and rural communities, they stress.

“These actions, combined with increasing awareness of the risk of type 2 diabetes and the importance of healthy diet intake, might be associated with a decrease in the burden of type 2 diabetes among adults in the U.S.,” the researchers add.

The data were published online Oct. 29 in JAMA Network Open.

“The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents,” commented Lorna Thorpe, PhD, MPH, professor in the department of population health at NYU Langone and senior author of the study in a press release.

In an accompanying editorial, Elham Hatef, MD, MPH, of the Center for Population Health IT at Johns Hopkins Bloomberg School of Public Health, Baltimore, calls the study “a great example of the capabilities of [health information technology] to provide a comprehensive assessment of a person’s health, which goes beyond just documenting clinical diseases and medical interventions.”
 

Research has large geographic breadth

The study is notable for its large geographic breadth, say the researchers.

“Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas,” Ms. Kanchi said in the press statement.

“Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not,” Ms. Kanchi continued.

The research included data for 4,100,650 individuals from the Veterans Affairs electronic health records (EHRs) who didn’t have type 2 diabetes at baseline, between 2008 and 2016. After a median follow-up of 5.5 person-years, 13.2% developed type 2 diabetes. Cumulative incidence was greater among those who were older, those who were non-Hispanic Black compared with other races, and those with disabilities and lower incomes.

The proportion of adults with type 2 diabetes was highest among those living in high-density urban communities (14.3%), followed by low-density urban (13.1%), rural (13.2%), and suburban (12.6%) communities.

Overall, a 10% increase in the number of fast food restaurants compared with other food establishments in a given neighborhood was associated with a 1% increased risk for incident type 2 diabetes in high-density urban, low-density urban, and rural communities and a 2% increased risk in suburban communities.

In contrast, a 10% increase in supermarket density compared with other food stores was associated with a lower risk for type 2 diabetes in suburban and rural communities, but the association wasn’t significant elsewhere.

“Taken together, our findings suggest that policies specific to fast food restaurants, such as [those] ... restricting the siting of fast food restaurants and healthy beverage default laws, may be effective in reducing type 2 diabetes risk in all community types,” say the authors.

“In urban areas where population and retail density are growing, it will be even more important to focus on these policies,” they emphasize.
 

Great example of capabilities of health information technology

In the editorial, Dr. Hatef notes that methodological advances, such as natural language processing and machine learning, have enabled health systems to use real-world data such as the free-text notes in the EHR to identify patient-level risk factors for diseases or disease complications.

Such methods could be further used to “evaluate the associations between social needs and place-based [social determinants of health] and type 2 diabetes incidence and management,” Dr. Hatef adds.

And linkage of data from the EHR to such community-level data “would help to comprehensively assess and identify patients likely to experience type 2 diabetes and its complications as a result of their risk factors or characteristics of the neighborhoods where they reside.”

“This approach could foster collaborations between the health systems and at-risk communities they serve and help to reallocate health system resources to those in most need in the community to reduce the burden of type 2 diabetes and other chronic conditions among racial minority groups and socioeconomically disadvantaged patients and to advance population health.”

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the Commonwealth Universal Research Enhancement program funded by the Pennsylvania Department of Health, the Urban Health Collaborative at Drexel University, and the Built Environment and Health Research Group at Columbia University. Ms. Kanchi and Dr. Hatef have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The more fast food restaurants a person lives near in the United States, the more likely they are to develop type 2 diabetes, new research indicates.  

The national study of more than 4 million U.S. veterans also found the opposite association with supermarkets in suburban and rural communities but not others.

“Neighborhood food environment was associated with type 2 diabetes risk among U.S. veterans in multiple community types, suggesting potential avenues for action to address the burden of type 2 diabetes,” say Rania Kanchi, MPH, of the department of population health, New York University Langone Health, and colleagues.

Restriction of fast food establishments could benefit all types of communities, while interventions to increase supermarket availability could help minimize diabetes risk in suburban and rural communities, they stress.

“These actions, combined with increasing awareness of the risk of type 2 diabetes and the importance of healthy diet intake, might be associated with a decrease in the burden of type 2 diabetes among adults in the U.S.,” the researchers add.

The data were published online Oct. 29 in JAMA Network Open.

“The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents,” commented Lorna Thorpe, PhD, MPH, professor in the department of population health at NYU Langone and senior author of the study in a press release.

In an accompanying editorial, Elham Hatef, MD, MPH, of the Center for Population Health IT at Johns Hopkins Bloomberg School of Public Health, Baltimore, calls the study “a great example of the capabilities of [health information technology] to provide a comprehensive assessment of a person’s health, which goes beyond just documenting clinical diseases and medical interventions.”
 

Research has large geographic breadth

The study is notable for its large geographic breadth, say the researchers.

“Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas,” Ms. Kanchi said in the press statement.

“Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not,” Ms. Kanchi continued.

The research included data for 4,100,650 individuals from the Veterans Affairs electronic health records (EHRs) who didn’t have type 2 diabetes at baseline, between 2008 and 2016. After a median follow-up of 5.5 person-years, 13.2% developed type 2 diabetes. Cumulative incidence was greater among those who were older, those who were non-Hispanic Black compared with other races, and those with disabilities and lower incomes.

The proportion of adults with type 2 diabetes was highest among those living in high-density urban communities (14.3%), followed by low-density urban (13.1%), rural (13.2%), and suburban (12.6%) communities.

Overall, a 10% increase in the number of fast food restaurants compared with other food establishments in a given neighborhood was associated with a 1% increased risk for incident type 2 diabetes in high-density urban, low-density urban, and rural communities and a 2% increased risk in suburban communities.

In contrast, a 10% increase in supermarket density compared with other food stores was associated with a lower risk for type 2 diabetes in suburban and rural communities, but the association wasn’t significant elsewhere.

“Taken together, our findings suggest that policies specific to fast food restaurants, such as [those] ... restricting the siting of fast food restaurants and healthy beverage default laws, may be effective in reducing type 2 diabetes risk in all community types,” say the authors.

“In urban areas where population and retail density are growing, it will be even more important to focus on these policies,” they emphasize.
 

Great example of capabilities of health information technology

In the editorial, Dr. Hatef notes that methodological advances, such as natural language processing and machine learning, have enabled health systems to use real-world data such as the free-text notes in the EHR to identify patient-level risk factors for diseases or disease complications.

Such methods could be further used to “evaluate the associations between social needs and place-based [social determinants of health] and type 2 diabetes incidence and management,” Dr. Hatef adds.

And linkage of data from the EHR to such community-level data “would help to comprehensively assess and identify patients likely to experience type 2 diabetes and its complications as a result of their risk factors or characteristics of the neighborhoods where they reside.”

“This approach could foster collaborations between the health systems and at-risk communities they serve and help to reallocate health system resources to those in most need in the community to reduce the burden of type 2 diabetes and other chronic conditions among racial minority groups and socioeconomically disadvantaged patients and to advance population health.”

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the Commonwealth Universal Research Enhancement program funded by the Pennsylvania Department of Health, the Urban Health Collaborative at Drexel University, and the Built Environment and Health Research Group at Columbia University. Ms. Kanchi and Dr. Hatef have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A “green” adaptation to the traditional Mediterranean diet could help improve insulin sensitivity and reduce visceral fat by increasing levels of ghrelin, the “hunger hormone,” new research suggests.

The current study is a new analysis of data from the randomized DIRECT-PLUS trial, which showed that the addition of green tea and substitution of red meat for a plant-based (Mankai) protein shake at dinner – dubbed the “green Mediterranean diet” – resulted in further improved cardiometabolic benefits compared with the traditional Mediterranean diet among people with baseline abdominal obesity and/or dyslipidemia, according to the researchers.

They specifically looked at ghrelin, nicknamed the “hunger hormone,” a neuropeptide mainly secreted by the gastric epithelium. It acts on the pituitary gland to release growth hormone. Ghrelin concentrations increase during fasting and decrease after eating. Lower levels are associated with insulin resistance and obesity.

Fasting ghrelin levels were elevated with weight loss, but those increases were associated with improved insulin sensitivity and regression of visceral adipose tissue even beyond weight loss.

Although the caloric restriction and weight loss were comparable with the two Mediterranean diets, the green Mediterranean diet group had double the increase in fasting ghrelin as the traditional Mediterranean diet group, the researchers point out in their report .
 

‘Hypothesis-generating’ study pushes many hot topic buttons

“This specific study is the first to show that ghrelin levels play an important role in metabolic adaptation to a dietary or lifestyle intervention and that ghrelin is an important player in the axis of adiposity, insulin resistance, and metabolic health,” lead researcher Gal Tsaban, MD, told this news organization.

The data partially explain some of the prior beneficial effects seen with the Green Mediterranean diet, even after adjustment for weight loss, he explained, noting that the revised version of the diet “could be considered as an alternative lifestyle intervention with possible metabolic benefits even beyond the Mediterranean diet, which is what we currently recommend for patients.”

Asked for comment, Christopher Gardner, PhD, was not as enthusiastic.

He took issue with the fact that ghrelin wasn’t a primary or even a prespecified secondary outcome of the DIRECT-PLUS trial and because the specific plant-based ingredients of the green Mediterranean diet used in the study may not be widely available or desirable and therefore limit the study’s generalizability.

Dr. Gardner, who is director of nutrition studies at the Stanford Prevention Research Center, California, also said: “They’re tying lots of interesting things together. The Mediterranean diet is a cool thing, ghrelin is a cool thing, and insulin resistance is hugely important in this day and age, even though we don’t all agree on how to measure it.”

“But it gets tough as you try to link them all together for an exploratory outcome. ... To me it’s an interesting hypothesis-generating study that pushes a lot of interesting buttons that are hot topics in the field.”
 

Green Mediterranean diet led to higher ghrelin, metabolic benefits

In DIRECT-PLUS, a total of 294 adults (88% men) older than 30 years of age with abdominal obesity (waist circumference >102 cm for men or >88 cm for women), or dyslipidemia (triglycerides >150 mg/dL and HDL-cholesterol ≤40 mg/dL for men or ≤50 mg/dL for women) were included. Half had prediabetes or type 2 diabetes.

They were randomized to one of three diets: a diet based on standard healthy dietary guidelines; a traditional Mediterranean diet low in simple carbohydrates, rich in vegetables, with poultry and fish replacing beef and lamb and 28 g/day of walnuts; or the Green-Mediterranean diet, including 3-4 cups/day of green tea and 100 g/day of a green shake made from the Mankai strain of Wolffia globosa (also known as duckweed) replacing dinner, and 28 g/day of walnuts.

The Green Mediterranean diet included 800 mg more polyphenols than the traditional Mediterranean diet. Both were equally calorie-restricted, at about 1,500-1,800 kcal/day for men and 1,200-1,400 kcal/day for women. All three groups were instructed to engage in regular physical activity and were given free gym memberships.

The retention rate was 98.3% after 6 months and 89.8% after 18 months.

Weight loss was similar between the two Mediterranean diet groups (2.9% and 3.9% for the traditional and green versions, respectively) compared with the standard healthy diet (0.6%) (P < .05 for both Mediterranean diet groups vs. control).

After 6 months, fasting ghrelin increased in the traditional (8.0%; P = .015) and green (10.5%; P = 0.031) Mediterranean groups versus baseline, with no significant change in the control group.

By 18 months, fasting ghrelin was significantly greater compared with baseline only in the green Mediterranean group (P = .012).

Because the differences in fasting ghrelin trajectories were only significant in men – likely due to the small sample size of women – a subsequent 18-month analysis was limited to the men. In a multivariate model adjusted for age, intervention group, baseline biomarker values, and 18-month weight changes, the 18-month change in fasting ghrelin remained a significant predictor for changes in A1c and homeostatic model of insulin resistance (HOMA-IR; P = .022).

Because weight loss remained the most significant predictor of improved insulin resistance, a further analysis examined the association between changes in fasting ghrelin levels with changes in the fraction of insulin resistance marker that were not attributed to weight loss, per se. With the other adjustments, fasting ghrelin was associated with residual reductions in A1c (P = .003), HOMA-IR (P = .021), increased HDL-cholesterol (P = .024), and relative visceral adipose tissue loss (P = .003).  
 

No specific product needed to push Mediterranean diet towards vegan

Dr. Tsaban, a nutritional researcher and cardiologist at Ben-Gurion University and Soroka University Medical Center, Be’er-Sheva, Israel, said the Mankai shake is commonly consumed in Israel but is also available worldwide. The study participants, all employees at an isolated nuclear research facility in the Negev, were particularly motivated. “They didn’t have a satiety problem with the drink. It made them very full,” he said. The manufacturer supplied the shakes but didn’t fund the study, he added.

However, Dr. Tsaban said that the “green Mediterranean diet” doesn’t depend on specific products.

Rather, “the concept is to push the Mediterranean diet a bit further and to replace the animal-based protein with vegetable-based protein, to shift your dietary habits towards a more vegan lifestyle. It’s not completely vegan, but it’s trending there. ... Our main goal was to increase the polyphenol intake, the antioxidant intake from vegetables. ... I think it can be replicated.”

Dr. Gardner said, “At the end of the day, it’s an exploratory study. ... It raises some interesting points that give the rest of us room to follow-up on.”

The study was funded by grants from the German Research Foundation, the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnut Commission. Dr. Tsaban has reported no further relevant financial relationships. Dr. Gardner has reported receiving study funding from Beyond Meat.

A version of this article first appeared on Medscape.com.

A “green” adaptation to the traditional Mediterranean diet could help improve insulin sensitivity and reduce visceral fat by increasing levels of ghrelin, the “hunger hormone,” new research suggests.

The current study is a new analysis of data from the randomized DIRECT-PLUS trial, which showed that the addition of green tea and substitution of red meat for a plant-based (Mankai) protein shake at dinner – dubbed the “green Mediterranean diet” – resulted in further improved cardiometabolic benefits compared with the traditional Mediterranean diet among people with baseline abdominal obesity and/or dyslipidemia, according to the researchers.

They specifically looked at ghrelin, nicknamed the “hunger hormone,” a neuropeptide mainly secreted by the gastric epithelium. It acts on the pituitary gland to release growth hormone. Ghrelin concentrations increase during fasting and decrease after eating. Lower levels are associated with insulin resistance and obesity.

Fasting ghrelin levels were elevated with weight loss, but those increases were associated with improved insulin sensitivity and regression of visceral adipose tissue even beyond weight loss.

Although the caloric restriction and weight loss were comparable with the two Mediterranean diets, the green Mediterranean diet group had double the increase in fasting ghrelin as the traditional Mediterranean diet group, the researchers point out in their report .
 

‘Hypothesis-generating’ study pushes many hot topic buttons

“This specific study is the first to show that ghrelin levels play an important role in metabolic adaptation to a dietary or lifestyle intervention and that ghrelin is an important player in the axis of adiposity, insulin resistance, and metabolic health,” lead researcher Gal Tsaban, MD, told this news organization.

The data partially explain some of the prior beneficial effects seen with the Green Mediterranean diet, even after adjustment for weight loss, he explained, noting that the revised version of the diet “could be considered as an alternative lifestyle intervention with possible metabolic benefits even beyond the Mediterranean diet, which is what we currently recommend for patients.”

Asked for comment, Christopher Gardner, PhD, was not as enthusiastic.

He took issue with the fact that ghrelin wasn’t a primary or even a prespecified secondary outcome of the DIRECT-PLUS trial and because the specific plant-based ingredients of the green Mediterranean diet used in the study may not be widely available or desirable and therefore limit the study’s generalizability.

Dr. Gardner, who is director of nutrition studies at the Stanford Prevention Research Center, California, also said: “They’re tying lots of interesting things together. The Mediterranean diet is a cool thing, ghrelin is a cool thing, and insulin resistance is hugely important in this day and age, even though we don’t all agree on how to measure it.”

“But it gets tough as you try to link them all together for an exploratory outcome. ... To me it’s an interesting hypothesis-generating study that pushes a lot of interesting buttons that are hot topics in the field.”
 

Green Mediterranean diet led to higher ghrelin, metabolic benefits

In DIRECT-PLUS, a total of 294 adults (88% men) older than 30 years of age with abdominal obesity (waist circumference >102 cm for men or >88 cm for women), or dyslipidemia (triglycerides >150 mg/dL and HDL-cholesterol ≤40 mg/dL for men or ≤50 mg/dL for women) were included. Half had prediabetes or type 2 diabetes.

They were randomized to one of three diets: a diet based on standard healthy dietary guidelines; a traditional Mediterranean diet low in simple carbohydrates, rich in vegetables, with poultry and fish replacing beef and lamb and 28 g/day of walnuts; or the Green-Mediterranean diet, including 3-4 cups/day of green tea and 100 g/day of a green shake made from the Mankai strain of Wolffia globosa (also known as duckweed) replacing dinner, and 28 g/day of walnuts.

The Green Mediterranean diet included 800 mg more polyphenols than the traditional Mediterranean diet. Both were equally calorie-restricted, at about 1,500-1,800 kcal/day for men and 1,200-1,400 kcal/day for women. All three groups were instructed to engage in regular physical activity and were given free gym memberships.

The retention rate was 98.3% after 6 months and 89.8% after 18 months.

Weight loss was similar between the two Mediterranean diet groups (2.9% and 3.9% for the traditional and green versions, respectively) compared with the standard healthy diet (0.6%) (P < .05 for both Mediterranean diet groups vs. control).

After 6 months, fasting ghrelin increased in the traditional (8.0%; P = .015) and green (10.5%; P = 0.031) Mediterranean groups versus baseline, with no significant change in the control group.

By 18 months, fasting ghrelin was significantly greater compared with baseline only in the green Mediterranean group (P = .012).

Because the differences in fasting ghrelin trajectories were only significant in men – likely due to the small sample size of women – a subsequent 18-month analysis was limited to the men. In a multivariate model adjusted for age, intervention group, baseline biomarker values, and 18-month weight changes, the 18-month change in fasting ghrelin remained a significant predictor for changes in A1c and homeostatic model of insulin resistance (HOMA-IR; P = .022).

Because weight loss remained the most significant predictor of improved insulin resistance, a further analysis examined the association between changes in fasting ghrelin levels with changes in the fraction of insulin resistance marker that were not attributed to weight loss, per se. With the other adjustments, fasting ghrelin was associated with residual reductions in A1c (P = .003), HOMA-IR (P = .021), increased HDL-cholesterol (P = .024), and relative visceral adipose tissue loss (P = .003).  
 

No specific product needed to push Mediterranean diet towards vegan

Dr. Tsaban, a nutritional researcher and cardiologist at Ben-Gurion University and Soroka University Medical Center, Be’er-Sheva, Israel, said the Mankai shake is commonly consumed in Israel but is also available worldwide. The study participants, all employees at an isolated nuclear research facility in the Negev, were particularly motivated. “They didn’t have a satiety problem with the drink. It made them very full,” he said. The manufacturer supplied the shakes but didn’t fund the study, he added.

However, Dr. Tsaban said that the “green Mediterranean diet” doesn’t depend on specific products.

Rather, “the concept is to push the Mediterranean diet a bit further and to replace the animal-based protein with vegetable-based protein, to shift your dietary habits towards a more vegan lifestyle. It’s not completely vegan, but it’s trending there. ... Our main goal was to increase the polyphenol intake, the antioxidant intake from vegetables. ... I think it can be replicated.”

Dr. Gardner said, “At the end of the day, it’s an exploratory study. ... It raises some interesting points that give the rest of us room to follow-up on.”

The study was funded by grants from the German Research Foundation, the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnut Commission. Dr. Tsaban has reported no further relevant financial relationships. Dr. Gardner has reported receiving study funding from Beyond Meat.

A version of this article first appeared on Medscape.com.

A “green” adaptation to the traditional Mediterranean diet could help improve insulin sensitivity and reduce visceral fat by increasing levels of ghrelin, the “hunger hormone,” new research suggests.

The current study is a new analysis of data from the randomized DIRECT-PLUS trial, which showed that the addition of green tea and substitution of red meat for a plant-based (Mankai) protein shake at dinner – dubbed the “green Mediterranean diet” – resulted in further improved cardiometabolic benefits compared with the traditional Mediterranean diet among people with baseline abdominal obesity and/or dyslipidemia, according to the researchers.

They specifically looked at ghrelin, nicknamed the “hunger hormone,” a neuropeptide mainly secreted by the gastric epithelium. It acts on the pituitary gland to release growth hormone. Ghrelin concentrations increase during fasting and decrease after eating. Lower levels are associated with insulin resistance and obesity.

Fasting ghrelin levels were elevated with weight loss, but those increases were associated with improved insulin sensitivity and regression of visceral adipose tissue even beyond weight loss.

Although the caloric restriction and weight loss were comparable with the two Mediterranean diets, the green Mediterranean diet group had double the increase in fasting ghrelin as the traditional Mediterranean diet group, the researchers point out in their report .
 

‘Hypothesis-generating’ study pushes many hot topic buttons

“This specific study is the first to show that ghrelin levels play an important role in metabolic adaptation to a dietary or lifestyle intervention and that ghrelin is an important player in the axis of adiposity, insulin resistance, and metabolic health,” lead researcher Gal Tsaban, MD, told this news organization.

The data partially explain some of the prior beneficial effects seen with the Green Mediterranean diet, even after adjustment for weight loss, he explained, noting that the revised version of the diet “could be considered as an alternative lifestyle intervention with possible metabolic benefits even beyond the Mediterranean diet, which is what we currently recommend for patients.”

Asked for comment, Christopher Gardner, PhD, was not as enthusiastic.

He took issue with the fact that ghrelin wasn’t a primary or even a prespecified secondary outcome of the DIRECT-PLUS trial and because the specific plant-based ingredients of the green Mediterranean diet used in the study may not be widely available or desirable and therefore limit the study’s generalizability.

Dr. Gardner, who is director of nutrition studies at the Stanford Prevention Research Center, California, also said: “They’re tying lots of interesting things together. The Mediterranean diet is a cool thing, ghrelin is a cool thing, and insulin resistance is hugely important in this day and age, even though we don’t all agree on how to measure it.”

“But it gets tough as you try to link them all together for an exploratory outcome. ... To me it’s an interesting hypothesis-generating study that pushes a lot of interesting buttons that are hot topics in the field.”
 

Green Mediterranean diet led to higher ghrelin, metabolic benefits

In DIRECT-PLUS, a total of 294 adults (88% men) older than 30 years of age with abdominal obesity (waist circumference >102 cm for men or >88 cm for women), or dyslipidemia (triglycerides >150 mg/dL and HDL-cholesterol ≤40 mg/dL for men or ≤50 mg/dL for women) were included. Half had prediabetes or type 2 diabetes.

They were randomized to one of three diets: a diet based on standard healthy dietary guidelines; a traditional Mediterranean diet low in simple carbohydrates, rich in vegetables, with poultry and fish replacing beef and lamb and 28 g/day of walnuts; or the Green-Mediterranean diet, including 3-4 cups/day of green tea and 100 g/day of a green shake made from the Mankai strain of Wolffia globosa (also known as duckweed) replacing dinner, and 28 g/day of walnuts.

The Green Mediterranean diet included 800 mg more polyphenols than the traditional Mediterranean diet. Both were equally calorie-restricted, at about 1,500-1,800 kcal/day for men and 1,200-1,400 kcal/day for women. All three groups were instructed to engage in regular physical activity and were given free gym memberships.

The retention rate was 98.3% after 6 months and 89.8% after 18 months.

Weight loss was similar between the two Mediterranean diet groups (2.9% and 3.9% for the traditional and green versions, respectively) compared with the standard healthy diet (0.6%) (P < .05 for both Mediterranean diet groups vs. control).

After 6 months, fasting ghrelin increased in the traditional (8.0%; P = .015) and green (10.5%; P = 0.031) Mediterranean groups versus baseline, with no significant change in the control group.

By 18 months, fasting ghrelin was significantly greater compared with baseline only in the green Mediterranean group (P = .012).

Because the differences in fasting ghrelin trajectories were only significant in men – likely due to the small sample size of women – a subsequent 18-month analysis was limited to the men. In a multivariate model adjusted for age, intervention group, baseline biomarker values, and 18-month weight changes, the 18-month change in fasting ghrelin remained a significant predictor for changes in A1c and homeostatic model of insulin resistance (HOMA-IR; P = .022).

Because weight loss remained the most significant predictor of improved insulin resistance, a further analysis examined the association between changes in fasting ghrelin levels with changes in the fraction of insulin resistance marker that were not attributed to weight loss, per se. With the other adjustments, fasting ghrelin was associated with residual reductions in A1c (P = .003), HOMA-IR (P = .021), increased HDL-cholesterol (P = .024), and relative visceral adipose tissue loss (P = .003).  
 

No specific product needed to push Mediterranean diet towards vegan

Dr. Tsaban, a nutritional researcher and cardiologist at Ben-Gurion University and Soroka University Medical Center, Be’er-Sheva, Israel, said the Mankai shake is commonly consumed in Israel but is also available worldwide. The study participants, all employees at an isolated nuclear research facility in the Negev, were particularly motivated. “They didn’t have a satiety problem with the drink. It made them very full,” he said. The manufacturer supplied the shakes but didn’t fund the study, he added.

However, Dr. Tsaban said that the “green Mediterranean diet” doesn’t depend on specific products.

Rather, “the concept is to push the Mediterranean diet a bit further and to replace the animal-based protein with vegetable-based protein, to shift your dietary habits towards a more vegan lifestyle. It’s not completely vegan, but it’s trending there. ... Our main goal was to increase the polyphenol intake, the antioxidant intake from vegetables. ... I think it can be replicated.”

Dr. Gardner said, “At the end of the day, it’s an exploratory study. ... It raises some interesting points that give the rest of us room to follow-up on.”

The study was funded by grants from the German Research Foundation, the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnut Commission. Dr. Tsaban has reported no further relevant financial relationships. Dr. Gardner has reported receiving study funding from Beyond Meat.

A version of this article first appeared on Medscape.com.

Trick-or-treaters may not be so easily tricked into loving sugar-free treats, thanks to taste buds hard-wired to seek calorie-containing sweets, a new study suggests.

Taste isn’t all about choosing peanut butter cups over jelly beans. Since earliest humanity, our sense of taste has helped us detect salty, sweet, sour, savory, and bitter so that we can choose foods high in energy and low in poisons.

But these new findings suggest that our taste buds have another hidden talent: identifying foods that don’t give us any energy at all.

Scientists suspected this ability after research in mice showed that their taste buds could distinguish between sugar and calorie-free artificial sweeteners.

To test this possibility in humans, scientists asked people to drink a series of clear beverages and identify whether they were plain water or sweetened. The goal was to compare how people responded to glucose – a natural caloric sweetener in fruits, honey, and table sugar – and sucralose, a calorie-free artificial sweetener.

All participants wore nose plugs, ensuring that they would use only their taste buds and not their sense of smell for detection.

As expected, people could easily tell plain water from sweetened drinks, whether with glucose or sucralose, confirming that taste buds detect sweetness.

In a twist, researchers then mixed in flavorless chemicals that block taste buds from picking up sweetness. With these drinks, people could no longer distinguish sucralose-sweetened beverages from plain water. But they could still tell when they had a beverage sweetened with glucose.

This finding indicates that two separate pathways underlie the mouth’s response to sugar, researchers report in PLOS One. The first pathway identifies sweet flavors, and the second one detects foods that contain energy that can be used for fuel.

Scientists might one day come up with calorie-free sweets that trick taste buds into detecting the presence of calories, enhancing their appeal. But in the lab studies, the participants had no visual cues or smell to guide their reactions, meaning how these other sensory inputs would affect treat perception isn’t known.

A version of this article first appeared on WebMD.com.

Trick-or-treaters may not be so easily tricked into loving sugar-free treats, thanks to taste buds hard-wired to seek calorie-containing sweets, a new study suggests.

Taste isn’t all about choosing peanut butter cups over jelly beans. Since earliest humanity, our sense of taste has helped us detect salty, sweet, sour, savory, and bitter so that we can choose foods high in energy and low in poisons.

But these new findings suggest that our taste buds have another hidden talent: identifying foods that don’t give us any energy at all.

Scientists suspected this ability after research in mice showed that their taste buds could distinguish between sugar and calorie-free artificial sweeteners.

To test this possibility in humans, scientists asked people to drink a series of clear beverages and identify whether they were plain water or sweetened. The goal was to compare how people responded to glucose – a natural caloric sweetener in fruits, honey, and table sugar – and sucralose, a calorie-free artificial sweetener.

All participants wore nose plugs, ensuring that they would use only their taste buds and not their sense of smell for detection.

As expected, people could easily tell plain water from sweetened drinks, whether with glucose or sucralose, confirming that taste buds detect sweetness.

In a twist, researchers then mixed in flavorless chemicals that block taste buds from picking up sweetness. With these drinks, people could no longer distinguish sucralose-sweetened beverages from plain water. But they could still tell when they had a beverage sweetened with glucose.

This finding indicates that two separate pathways underlie the mouth’s response to sugar, researchers report in PLOS One. The first pathway identifies sweet flavors, and the second one detects foods that contain energy that can be used for fuel.

Scientists might one day come up with calorie-free sweets that trick taste buds into detecting the presence of calories, enhancing their appeal. But in the lab studies, the participants had no visual cues or smell to guide their reactions, meaning how these other sensory inputs would affect treat perception isn’t known.

A version of this article first appeared on WebMD.com.

Trick-or-treaters may not be so easily tricked into loving sugar-free treats, thanks to taste buds hard-wired to seek calorie-containing sweets, a new study suggests.

Taste isn’t all about choosing peanut butter cups over jelly beans. Since earliest humanity, our sense of taste has helped us detect salty, sweet, sour, savory, and bitter so that we can choose foods high in energy and low in poisons.

But these new findings suggest that our taste buds have another hidden talent: identifying foods that don’t give us any energy at all.

Scientists suspected this ability after research in mice showed that their taste buds could distinguish between sugar and calorie-free artificial sweeteners.

To test this possibility in humans, scientists asked people to drink a series of clear beverages and identify whether they were plain water or sweetened. The goal was to compare how people responded to glucose – a natural caloric sweetener in fruits, honey, and table sugar – and sucralose, a calorie-free artificial sweetener.

All participants wore nose plugs, ensuring that they would use only their taste buds and not their sense of smell for detection.

As expected, people could easily tell plain water from sweetened drinks, whether with glucose or sucralose, confirming that taste buds detect sweetness.

In a twist, researchers then mixed in flavorless chemicals that block taste buds from picking up sweetness. With these drinks, people could no longer distinguish sucralose-sweetened beverages from plain water. But they could still tell when they had a beverage sweetened with glucose.

This finding indicates that two separate pathways underlie the mouth’s response to sugar, researchers report in PLOS One. The first pathway identifies sweet flavors, and the second one detects foods that contain energy that can be used for fuel.

Scientists might one day come up with calorie-free sweets that trick taste buds into detecting the presence of calories, enhancing their appeal. But in the lab studies, the participants had no visual cues or smell to guide their reactions, meaning how these other sensory inputs would affect treat perception isn’t known.

A version of this article first appeared on WebMD.com.

The “twincretin” tirzepatide scored another pivotal-trial win in full, published results from the multicenter SURPASS-4 trial, which compared the investigational agent to insulin glargine for treatment of type 2 diabetes. The study comprised 1,995 randomized patients with inadequately controlled type 2 diabetes and high cardiovascular disease risk.

Positive results for tirzepatide from SURPASS-4, the fifth and final registration trial for the drug, as well as in the other four studies, tee up the agent for a planned approval submission to the Food and Drug Administration by the end of 2021.

SURPASS-4 differed from the four other pivotal trials not only in its comparator agent, but also by being the longest of the five and the only one that, by design, enrolled exclusively patients with either established cardiovascular disease or high risk for the disease.

The new results “provide initial support for glycemic control [by tirzepatide] being sustained for more than 1 year,” wrote Stefano Del Prato, MD, and associates in their published report in The Lancet.

Despite the trial’s primary endpoint of change in hemoglobin A1c after 52 weeks on treatment, the study continued for another year and had a median time on treatment of 85 weeks, with 7% of enrolled patients remaining on treatment for the maximum on-treatment follow-up of 104 weeks.

Potent glycemic control

The primary endpoint showed that treatment with tirzepatide produced an average incremental reduction in A1c of 0.99% among 328 patients treated with a 10 mg weekly subcutaneous dosage compared with the 1,000 patients who received insulin glargine (Basaglar, Lantus, Toujeo), and an average 1.14% incremental reduction in A1c among 338 patients on a 15-mg dosage once weekly, reported Dr. Del Prato, professor and chief of the section of diabetes at the University of Pisa (Italy).

This met the prespecified criteria for noninferiority of tirzepatide to insulin glargine for reduction of A1c, the study’s primary objective, and also met the study’s prespecified definition of superiority, both statistically significant results. The study also tested a weekly tirzepatide dosage of 5 mg that was significantly superior to insulin glargine for glycemic control.

“The magnitude of A1c reduction and the proportions of patients reaching glycemic targets appear to be larger than in similar studies in which GLP-1 [glucagon-like peptide–1] receptor agonists have been compared with glargine,” the investigators wrote in their report.

The A1c effect of tirzepatide seen across all five SURPASS trials “surpasses what we’ve seen with other [glycemia control] drugs, with the possible exception of insulin,” said Jan W. Eriksson, MD, PhD, professor of clinical diabetes and metabolism at Uppsala (Sweden) University.

MDedge News

Safety appears similar to GLP-1 receptor agonists

The safety profile of tirzepatide in SURPASS-4, as it was in all of the other four trials in the SURPASS series, was consistent with previously reported safety of agents in the GLP-1 receptor agonist class, said Dr. Del Prato. It was an expected finding as tirzepatide combines activity as a GLP-1 receptor agonist with activity as a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist in a single molecule.

The most common adverse effects were gastrointestinal, including diarrhea, nausea, decreased appetite, and vomiting. Most of these effects were mild or moderate, and they occurred most often during dose escalation of tirzepatide in the first 24 weeks on treatment.

The GIP receptor agonist effect of tirzepatide may diminish the nausea experienced by patients as a result of the drug’s GLP-1 receptor agonist action, Dr. Eriksson, designated discussant for the SURPASS trials, said during a session Sept. 30 at the virtual annual meeting of the European Association for the Study of Diabetes (EASD).

Clinically significant or severe hypoglycemia occurred in 8% of all patients on tirzepatide, with no apparent dose relationship, about half the rate of the patients treated with insulin glargine. Notably, the hypoglycemia episodes among patients treated with tirzepatide clustered almost entirely in the subgroup of patients who also took a sulfonylurea agent during the study. (SURPASS-4 allowed enrolled patients to be on their background antidiabetes regimen throughout the study, and at baseline 95% were taking metformin, 54% were on a sulfonylurea, and about a quarter were on a sodium-glucose cotransporter-2 inhibitor.)

“I would advise not using tirzepatide with insulin or with a sulfonylurea,” Dr. Eriksson said. Aside from this risk for hypoglycemia when tirzepatide is used concurrently with certain other antidiabetes drugs, the SURPASS trials have shown “no other important safety signals,” Dr. Eriksson added.

Cardiovascular safety

All enrolled patients had either known coronary, cerebrovascular, or peripheral arterial disease or were at high risk for having one or more of these conditions because they were at least 50 years old with a history of either chronic kidney disease with depressed glomerular filtration or heart failure.

During complete follow-up, the composite rate of cardiovascular death, MI, stroke, or hospitalization for unstable angina was numerically less in the patients who received tirzepatide, 5%, than in those on insulin glargine, 6%, a 26% relative risk reduction that did not achieve significance. The rate of total mortality was 3% in the tirzepatide group and 4% among those on glargine, a 30% relative risk reduction that was not significant.

The cardiovascular disease outcomes “suggest that tirzepatide is safe from a cardiovascular perspective,” Dr. Del Prato said when he presented the SURPASS-4 results during the virtual annual meeting of the EASD. However, a much larger cardiovascular outcomes trial of tirzepatide, SURPASS-CVOT, with more than 12,000 randomized patients and using a GLP-1 receptor agonist as the comparator, is now in progress, with a report on the findings expected in 2025.

Sara Freeman/MDedge News

Overall, results from all five SURPASS trials of tirzepatide have shown that the drug is “effective and safe in people with type 2 diabetes, providing stringent glycemic control and additional metabolic benefits including weight reduction and an improvement in other cardiometabolic markers,” said Melanie J. Davies, MD, professor of diabetes medicine at the University of Leicester, England.

Looking forward to when tirzepatide will be available for routine use, Dr. Eriksson positioned it near-term as part of a dual or triple regimen, especially for patients with type 2 diabetes who are obese or have uncontrolled hyperglycemia, renal impairment, high cardiovascular disease risk, or high risk for clinically significant or severe hypoglycemia. 
A role for tirzepatide as a first-line agent is currently “more speculative,” he added, with more data needed on cardiovascular outcomes, long-term safety, and cost effectiveness.

The existing evidence base for tirzepatide shows “very promising efficacy” for weight loss and glucose lowering with “reassuring safety and tolerability,” and is a “very important addition to current options,” although the long-term safety of chronic tirzepatide treatment remains unproven, he said.

Dr. Eriksson called the drug’s glycemic control “strong and durable” based on the entire SURPASS program, with a “major” weight loss effect. He also suggested that while the adverse effect profile of tirzepatide appears similar to the GLP-1 receptor agonists, the incidence of gastrointestinal adverse events may be lower with tirzepatide.

SURPASS-4 and the other SURPASS trials were funded by Lilly, the company developing tirzepatide. Dr. Del Prato has ties with Lilly, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Merck Sharpe and Dohme, Novartis, Novo Nordisk, and Sanofi. Dr. Davies has ties with Lilly, AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Novo Nordisk, Sanofi-Aventis, Servier, Gilead Sciences, Napp Pharmaceuticals, Mitsubishi Tanabe, and Takeda. Dr. Eriksson has ties with AstraZeneca, Ilya Pharma, Merck Sharp & Dohme, and Novo Nordisk.

mzoler@mdedge.com

The “twincretin” tirzepatide scored another pivotal-trial win in full, published results from the multicenter SURPASS-4 trial, which compared the investigational agent to insulin glargine for treatment of type 2 diabetes. The study comprised 1,995 randomized patients with inadequately controlled type 2 diabetes and high cardiovascular disease risk.

Positive results for tirzepatide from SURPASS-4, the fifth and final registration trial for the drug, as well as in the other four studies, tee up the agent for a planned approval submission to the Food and Drug Administration by the end of 2021.

SURPASS-4 differed from the four other pivotal trials not only in its comparator agent, but also by being the longest of the five and the only one that, by design, enrolled exclusively patients with either established cardiovascular disease or high risk for the disease.

The new results “provide initial support for glycemic control [by tirzepatide] being sustained for more than 1 year,” wrote Stefano Del Prato, MD, and associates in their published report in The Lancet.

Despite the trial’s primary endpoint of change in hemoglobin A1c after 52 weeks on treatment, the study continued for another year and had a median time on treatment of 85 weeks, with 7% of enrolled patients remaining on treatment for the maximum on-treatment follow-up of 104 weeks.

Potent glycemic control

The primary endpoint showed that treatment with tirzepatide produced an average incremental reduction in A1c of 0.99% among 328 patients treated with a 10 mg weekly subcutaneous dosage compared with the 1,000 patients who received insulin glargine (Basaglar, Lantus, Toujeo), and an average 1.14% incremental reduction in A1c among 338 patients on a 15-mg dosage once weekly, reported Dr. Del Prato, professor and chief of the section of diabetes at the University of Pisa (Italy).

This met the prespecified criteria for noninferiority of tirzepatide to insulin glargine for reduction of A1c, the study’s primary objective, and also met the study’s prespecified definition of superiority, both statistically significant results. The study also tested a weekly tirzepatide dosage of 5 mg that was significantly superior to insulin glargine for glycemic control.

“The magnitude of A1c reduction and the proportions of patients reaching glycemic targets appear to be larger than in similar studies in which GLP-1 [glucagon-like peptide–1] receptor agonists have been compared with glargine,” the investigators wrote in their report.

The A1c effect of tirzepatide seen across all five SURPASS trials “surpasses what we’ve seen with other [glycemia control] drugs, with the possible exception of insulin,” said Jan W. Eriksson, MD, PhD, professor of clinical diabetes and metabolism at Uppsala (Sweden) University.

MDedge News

Safety appears similar to GLP-1 receptor agonists

The safety profile of tirzepatide in SURPASS-4, as it was in all of the other four trials in the SURPASS series, was consistent with previously reported safety of agents in the GLP-1 receptor agonist class, said Dr. Del Prato. It was an expected finding as tirzepatide combines activity as a GLP-1 receptor agonist with activity as a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist in a single molecule.

The most common adverse effects were gastrointestinal, including diarrhea, nausea, decreased appetite, and vomiting. Most of these effects were mild or moderate, and they occurred most often during dose escalation of tirzepatide in the first 24 weeks on treatment.

The GIP receptor agonist effect of tirzepatide may diminish the nausea experienced by patients as a result of the drug’s GLP-1 receptor agonist action, Dr. Eriksson, designated discussant for the SURPASS trials, said during a session Sept. 30 at the virtual annual meeting of the European Association for the Study of Diabetes (EASD).

Clinically significant or severe hypoglycemia occurred in 8% of all patients on tirzepatide, with no apparent dose relationship, about half the rate of the patients treated with insulin glargine. Notably, the hypoglycemia episodes among patients treated with tirzepatide clustered almost entirely in the subgroup of patients who also took a sulfonylurea agent during the study. (SURPASS-4 allowed enrolled patients to be on their background antidiabetes regimen throughout the study, and at baseline 95% were taking metformin, 54% were on a sulfonylurea, and about a quarter were on a sodium-glucose cotransporter-2 inhibitor.)

“I would advise not using tirzepatide with insulin or with a sulfonylurea,” Dr. Eriksson said. Aside from this risk for hypoglycemia when tirzepatide is used concurrently with certain other antidiabetes drugs, the SURPASS trials have shown “no other important safety signals,” Dr. Eriksson added.

Cardiovascular safety

All enrolled patients had either known coronary, cerebrovascular, or peripheral arterial disease or were at high risk for having one or more of these conditions because they were at least 50 years old with a history of either chronic kidney disease with depressed glomerular filtration or heart failure.

During complete follow-up, the composite rate of cardiovascular death, MI, stroke, or hospitalization for unstable angina was numerically less in the patients who received tirzepatide, 5%, than in those on insulin glargine, 6%, a 26% relative risk reduction that did not achieve significance. The rate of total mortality was 3% in the tirzepatide group and 4% among those on glargine, a 30% relative risk reduction that was not significant.

The cardiovascular disease outcomes “suggest that tirzepatide is safe from a cardiovascular perspective,” Dr. Del Prato said when he presented the SURPASS-4 results during the virtual annual meeting of the EASD. However, a much larger cardiovascular outcomes trial of tirzepatide, SURPASS-CVOT, with more than 12,000 randomized patients and using a GLP-1 receptor agonist as the comparator, is now in progress, with a report on the findings expected in 2025.

Sara Freeman/MDedge News

Overall, results from all five SURPASS trials of tirzepatide have shown that the drug is “effective and safe in people with type 2 diabetes, providing stringent glycemic control and additional metabolic benefits including weight reduction and an improvement in other cardiometabolic markers,” said Melanie J. Davies, MD, professor of diabetes medicine at the University of Leicester, England.

Looking forward to when tirzepatide will be available for routine use, Dr. Eriksson positioned it near-term as part of a dual or triple regimen, especially for patients with type 2 diabetes who are obese or have uncontrolled hyperglycemia, renal impairment, high cardiovascular disease risk, or high risk for clinically significant or severe hypoglycemia. 
A role for tirzepatide as a first-line agent is currently “more speculative,” he added, with more data needed on cardiovascular outcomes, long-term safety, and cost effectiveness.

The existing evidence base for tirzepatide shows “very promising efficacy” for weight loss and glucose lowering with “reassuring safety and tolerability,” and is a “very important addition to current options,” although the long-term safety of chronic tirzepatide treatment remains unproven, he said.

Dr. Eriksson called the drug’s glycemic control “strong and durable” based on the entire SURPASS program, with a “major” weight loss effect. He also suggested that while the adverse effect profile of tirzepatide appears similar to the GLP-1 receptor agonists, the incidence of gastrointestinal adverse events may be lower with tirzepatide.

SURPASS-4 and the other SURPASS trials were funded by Lilly, the company developing tirzepatide. Dr. Del Prato has ties with Lilly, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Merck Sharpe and Dohme, Novartis, Novo Nordisk, and Sanofi. Dr. Davies has ties with Lilly, AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Novo Nordisk, Sanofi-Aventis, Servier, Gilead Sciences, Napp Pharmaceuticals, Mitsubishi Tanabe, and Takeda. Dr. Eriksson has ties with AstraZeneca, Ilya Pharma, Merck Sharp & Dohme, and Novo Nordisk.

mzoler@mdedge.com

The “twincretin” tirzepatide scored another pivotal-trial win in full, published results from the multicenter SURPASS-4 trial, which compared the investigational agent to insulin glargine for treatment of type 2 diabetes. The study comprised 1,995 randomized patients with inadequately controlled type 2 diabetes and high cardiovascular disease risk.

Positive results for tirzepatide from SURPASS-4, the fifth and final registration trial for the drug, as well as in the other four studies, tee up the agent for a planned approval submission to the Food and Drug Administration by the end of 2021.

SURPASS-4 differed from the four other pivotal trials not only in its comparator agent, but also by being the longest of the five and the only one that, by design, enrolled exclusively patients with either established cardiovascular disease or high risk for the disease.

The new results “provide initial support for glycemic control [by tirzepatide] being sustained for more than 1 year,” wrote Stefano Del Prato, MD, and associates in their published report in The Lancet.

Despite the trial’s primary endpoint of change in hemoglobin A1c after 52 weeks on treatment, the study continued for another year and had a median time on treatment of 85 weeks, with 7% of enrolled patients remaining on treatment for the maximum on-treatment follow-up of 104 weeks.

Potent glycemic control

The primary endpoint showed that treatment with tirzepatide produced an average incremental reduction in A1c of 0.99% among 328 patients treated with a 10 mg weekly subcutaneous dosage compared with the 1,000 patients who received insulin glargine (Basaglar, Lantus, Toujeo), and an average 1.14% incremental reduction in A1c among 338 patients on a 15-mg dosage once weekly, reported Dr. Del Prato, professor and chief of the section of diabetes at the University of Pisa (Italy).

This met the prespecified criteria for noninferiority of tirzepatide to insulin glargine for reduction of A1c, the study’s primary objective, and also met the study’s prespecified definition of superiority, both statistically significant results. The study also tested a weekly tirzepatide dosage of 5 mg that was significantly superior to insulin glargine for glycemic control.

“The magnitude of A1c reduction and the proportions of patients reaching glycemic targets appear to be larger than in similar studies in which GLP-1 [glucagon-like peptide–1] receptor agonists have been compared with glargine,” the investigators wrote in their report.

The A1c effect of tirzepatide seen across all five SURPASS trials “surpasses what we’ve seen with other [glycemia control] drugs, with the possible exception of insulin,” said Jan W. Eriksson, MD, PhD, professor of clinical diabetes and metabolism at Uppsala (Sweden) University.

MDedge News

Safety appears similar to GLP-1 receptor agonists

The safety profile of tirzepatide in SURPASS-4, as it was in all of the other four trials in the SURPASS series, was consistent with previously reported safety of agents in the GLP-1 receptor agonist class, said Dr. Del Prato. It was an expected finding as tirzepatide combines activity as a GLP-1 receptor agonist with activity as a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist in a single molecule.

The most common adverse effects were gastrointestinal, including diarrhea, nausea, decreased appetite, and vomiting. Most of these effects were mild or moderate, and they occurred most often during dose escalation of tirzepatide in the first 24 weeks on treatment.

The GIP receptor agonist effect of tirzepatide may diminish the nausea experienced by patients as a result of the drug’s GLP-1 receptor agonist action, Dr. Eriksson, designated discussant for the SURPASS trials, said during a session Sept. 30 at the virtual annual meeting of the European Association for the Study of Diabetes (EASD).

Clinically significant or severe hypoglycemia occurred in 8% of all patients on tirzepatide, with no apparent dose relationship, about half the rate of the patients treated with insulin glargine. Notably, the hypoglycemia episodes among patients treated with tirzepatide clustered almost entirely in the subgroup of patients who also took a sulfonylurea agent during the study. (SURPASS-4 allowed enrolled patients to be on their background antidiabetes regimen throughout the study, and at baseline 95% were taking metformin, 54% were on a sulfonylurea, and about a quarter were on a sodium-glucose cotransporter-2 inhibitor.)

“I would advise not using tirzepatide with insulin or with a sulfonylurea,” Dr. Eriksson said. Aside from this risk for hypoglycemia when tirzepatide is used concurrently with certain other antidiabetes drugs, the SURPASS trials have shown “no other important safety signals,” Dr. Eriksson added.

Cardiovascular safety

All enrolled patients had either known coronary, cerebrovascular, or peripheral arterial disease or were at high risk for having one or more of these conditions because they were at least 50 years old with a history of either chronic kidney disease with depressed glomerular filtration or heart failure.

During complete follow-up, the composite rate of cardiovascular death, MI, stroke, or hospitalization for unstable angina was numerically less in the patients who received tirzepatide, 5%, than in those on insulin glargine, 6%, a 26% relative risk reduction that did not achieve significance. The rate of total mortality was 3% in the tirzepatide group and 4% among those on glargine, a 30% relative risk reduction that was not significant.

The cardiovascular disease outcomes “suggest that tirzepatide is safe from a cardiovascular perspective,” Dr. Del Prato said when he presented the SURPASS-4 results during the virtual annual meeting of the EASD. However, a much larger cardiovascular outcomes trial of tirzepatide, SURPASS-CVOT, with more than 12,000 randomized patients and using a GLP-1 receptor agonist as the comparator, is now in progress, with a report on the findings expected in 2025.

Sara Freeman/MDedge News

Overall, results from all five SURPASS trials of tirzepatide have shown that the drug is “effective and safe in people with type 2 diabetes, providing stringent glycemic control and additional metabolic benefits including weight reduction and an improvement in other cardiometabolic markers,” said Melanie J. Davies, MD, professor of diabetes medicine at the University of Leicester, England.

Looking forward to when tirzepatide will be available for routine use, Dr. Eriksson positioned it near-term as part of a dual or triple regimen, especially for patients with type 2 diabetes who are obese or have uncontrolled hyperglycemia, renal impairment, high cardiovascular disease risk, or high risk for clinically significant or severe hypoglycemia. 
A role for tirzepatide as a first-line agent is currently “more speculative,” he added, with more data needed on cardiovascular outcomes, long-term safety, and cost effectiveness.

The existing evidence base for tirzepatide shows “very promising efficacy” for weight loss and glucose lowering with “reassuring safety and tolerability,” and is a “very important addition to current options,” although the long-term safety of chronic tirzepatide treatment remains unproven, he said.

Dr. Eriksson called the drug’s glycemic control “strong and durable” based on the entire SURPASS program, with a “major” weight loss effect. He also suggested that while the adverse effect profile of tirzepatide appears similar to the GLP-1 receptor agonists, the incidence of gastrointestinal adverse events may be lower with tirzepatide.

SURPASS-4 and the other SURPASS trials were funded by Lilly, the company developing tirzepatide. Dr. Del Prato has ties with Lilly, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Merck Sharpe and Dohme, Novartis, Novo Nordisk, and Sanofi. Dr. Davies has ties with Lilly, AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Novo Nordisk, Sanofi-Aventis, Servier, Gilead Sciences, Napp Pharmaceuticals, Mitsubishi Tanabe, and Takeda. Dr. Eriksson has ties with AstraZeneca, Ilya Pharma, Merck Sharp & Dohme, and Novo Nordisk.

mzoler@mdedge.com

Agents that form the sodium-glucose cotransporter 2 inhibitor class – including canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – have show remarkably consistent cardiovascular efficacy and safety for treating patients with heart failure, chronic kidney disease, and higher-risk patients with type 2 diabetes.

But despite an essential role now established for drugs in the SGLT2 inhibitor class for patients with heart failure with reduced ejection fraction, progressive renal dysfunction, or – most recently – patients with heart failure with preserved ejection fraction, the scope may be less clear when using these agents in patients with type 2 diabetes because they fall across a broad spectrum of risk for cardiorenal disease.

“What makes patients with type 2 diabetes distinct from other patients in whom SGLT2 inhibitors have been studied, such as patients with heart failure, is that they have a much wider spectrum of risk. Low-risk patients with type 2 diabetes were not included in the SGLT2 inhibitor trials. Defining risk in patients with type 2 diabetes has the potential to inform prioritization” for treatment with an SGLT2 inhibitor, explained David D. Berg, MD, who has led one effort to develop risk scores that can risk-stratify patients with type 2 diabetes based on their vulnerability to incident heart failure and hospitalization for these episodes,

The hefty cost for these drugs, with retail prices that run over $6,000 annually for the most widely used and most potent agents in the class, has spurred researchers to try to find cost-effective ways to identify patients with type 2 diabetes who stand to benefit most from taking an SGLT2 inhibitor.
 

‘Cost must be considered’

“Cost must be considered, and at this point it’s probably more responsible on a societal level to advise using SGLT2 inhibitors mainly in patients [with type 2 diabetes] with compelling indications,” said Silvio Inzucchi, MD, professor and director of the Yale Medicine Diabetes Center in New Haven, Conn. Dr. Inzucchi added, however, that “I can easily foresee a day when these agents are considered foundational therapy for all patients with type 2 diabetes, after they go generic and cost is not a major issue. I’m starting to lean toward this very simplified approach, but the costs are prohibitive at this time.”

“If the SGLT2 inhibitors were available at a low cost, I’d argue that they should be used in all patients with type 2 diabetes who have no contraindications or tolerability issues; but we live in a world where they are not yet low cost,” agreed Mikhail N. Kosiborod, MD, a cardiologist and codirector of the Cardiometabolic Center of Excellence at Saint Luke’s Mid-America Heart Institute in Kansas City, Mo.

“We can’t give SGLT2 inhibitors to everyone with type 2 diabetes right now because that would be too costly; these agents are so expensive. You start by targeting the patients with the highest risk” for incident heart failure, said Ambarish Pandey, MD, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

The spotlight the SGLT2 inhibitor class has received, based on its unexpectedly potent efficacy in cutting rates of acute heart failure episodes in patients with type 2 diabetes, has also sharply raised the profile of this complication of type 2 diabetes, an outcome that until recently many clinicians had largely ignored, overshadowed by a focus on adverse outcomes from atherosclerotic cardiovascular disease such as MIs and strokes.

“Results from the SGLT2 inhibitor trials have reignited interest in the relationship between type 2 diabetes and heart failure and have started to shift the mindset of clinicians toward thinking about reducing both atherothrombotic risk and heart failure risk in patients with type 2 diabetes,” said Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston.

“Prior to the SGLT2 inhibitor trials, heart failure was on the radar of diabetes clinicians only as something to watch for as a potential side effect of certain glucose-lowering therapies. Now that there are therapies that can lower heart failure hospitalization, it’s made us think more about heart failure, how common it is in patients with type 2 diabetes, and what can we do to lower this risk,” commented Alice Y.Y. Cheng, MD, a diabetes specialist at the University of Toronto.
 

Banking on biomarkers

Risk scores for assessing the likelihood of people developing incident heart failure date back more than a decade. More recent efforts have focused on patients with type 2 diabetes, starting with scores that relied entirely on clinical markers of risk such as prior heart failure, established coronary artery disease, and chronic kidney disease. Reports of two of these validated scores appeared in 2019, one from a team led by Dr. Berg and associates in 2019, and a second score developed by Dr. Pandey and associates.

More recently, both research teams behind these two scores validated newer versions that further refined assessment of patients with diabetes by including biomarkers of incipient heart failure, such as N-terminal of the prohormone brain natriuretic peptide (NT-proBNP). The UT Southwestern group’s biomarker-based score relies on levels of NT-proBNP as well as on levels of high sensitivity troponin T (hsTnT) and C-reactive protein, plus ECG-based assessment of left ventricular hypertrophy to assess risk for incident heart failure. Developers reported in 2021 that this biomarker score could account for 74% (C-statistic) of the 5-year risk for heart failure among patients with diabetes.

The biomarker-based score devised by Dr. Berg and associates, relies on NT-proBNP, hsTnT, and a history of heart failure to predict the risk for a future hospitalization for heart failure. They reported in Diabetes Care that in validation testing this score accounted for 84% of the risk.

“I’m hopeful that both our original clinically-based risk score and our new biomarker-based score will be endorsed by professional society guidelines. The intent of the biomarker-based score is not to replace the clinical one,” Dr. Berg stressed in an interview. But he acknowledged that it uses biomarker values that currently are not routinely collected in U.S. practice. Biomarkers like NT-proBNP “are highly associated with future heart failure risk, but are not yet routinely assessed,” he said. Because of this, “widespread adoption of the [biomarker] risk tool will require some education.”

It may also require some sort of preliminary screening to determine the appropriateness of using it in a specific patient because of the relative expense of a test for NT-proBNP.

A Texas two-step process

“We can’t perform a [NT-proBNP] test on every patient with type 2 diabetes because cost is a huge barrier,” with a U.K. price of roughly £28 (about $40) per test, commented Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow. “NT-proBNP is the best biomarker by far to predict risk” for heart failure,” but “it’s too expensive. It’s not going to happen in everyone,” he said in an interview. He suggested taking a two-step approach to identify patients to test for NT-proBNP based on clinical measures like blood pressure, weight and height, lipid levels and renal function and the presence of suggestive symptoms like dyspnea, fatigue, and peripheral edema, an argument he recently spelled out in detail in an editorial he coauthored.

“More work is needed to define which patients would usefully have cardiac biomarkers measured,” Dr. Sattar wrote with his associate.

Two-step is the approach used in routine practice by clinicians at UT Southwestern Medical Center. “We screen all patients with type 2 diabetes and no diagnosed heart failure who are not already on an SGLT2 inhibitor” using their 2019 screening tool, called the WATCH-DM Risk score, said Dr. Pandey. Patients flagged at high risk by their clinical score receive an SGLT2 inhibitor (presuming no contraindications). The remaining patients with low or intermediate risk may then undergo biomarker-based assessment to find additional patients who warrant SGLT2 inhibitor treatment, he said in an interview.

Often, a record of the most important biomarker, NT-proBNP, is already in the patient’s record and less than a year old, in which case clinicians use that value. An NT-proBNP level of at least 125 pg/mL indicates increased risk in people with a body mass index of less than 30 kg/m², while for those with higher body mass indexes clinicians at Southwestern apply a threshold for higher risk of at least 100 pg/mL.

In addition to starting those patients on an SGLT2 inhibitor, the Southwestern protocol calls for intensified efforts at weight loss and improved fitness to further lower incident heart failure risk, and they are also considering targeting treatment with a glucagonlike peptide–1 receptor agonist to these patients as well. They have a research protocol in place, called WATCH-DM, that will prospectively assess the efficacy of this strategy.

Despite the cost, others also believe that the time is right for biomarker-based tests to boost access to the benefits that treatment with SGLT2 inhibitors can give patients with type 2 diabetes.

“In theory it’s reasonable” to use a risk score like the recent one reported by Dr. Berg and coauthors, said Vanita R. Aroda, MD, an endocrinologist and director of diabetes clinical research at Brigham and Women’s Hospital in Boston. “We need to pay attention to heart failure as an outcome and use risk stratification” to decide which patients with type 2 diabetes but without established cardiovascular disease warrant treatment with an SGLT2 inhibitor, she said in an interview. “Given the data, we need more concrete recommendations” from medical societies on how to reasonably use biomarkers and imaging to identify patients with type 2 diabetes who are at increased risk for heart failure and hence would benefit from treatment. “This should be of high interest to guidelines committees,” she added.

The earlier version of Dr. Berg’s score, based exclusively on clinical observations and conventional measures like estimated glomerular filtration rate and urinary creatinine to albumin ratio, had overlap with established criteria for starting treatment with an SGLT2 inhibitor, such as the presence of chronic kidney disease, she noted. “A biomarker-based score may provide the additional level of discrimination needed to characterize risk and potential benefit.”
 

Asymptomatic diabetic cardiomyopathy

Dr. Aroda and several coauthors recently published a review that describes a subset of patients with type 2 diabetes who might get picked up by intensified screening for heart failure risk: those with asymptomatic diabetic cardiomyopathy, a clinical state that they said represents patients with stage B heart failure based on the new Universal Definition and Classification of Heart Failure. Until recently, these patients with type 2 diabetes and asymptomatic cardiomyopathy have mostly gone unrecognized.

A recent report from Dr. Pandey and associates reviewed records from 2,900 U.S. patients with diabetes and no symptoms who had been included in any of three cohort studies and found echocardiographic evidence of early-stage cardiomyopathy in as many as two-thirds. In an editorial about this report, Dr. Aroda and coauthors called these patients a potential “window of opportunity for prevention and treatment of heart failure.”

“There is evidence of structural cardiac changes that progress through the stages of heart failure,” and starting treatment with an SGLT2 inhibitor during an earlier stage can potentially slow or prevent this progression and thereby limit future functional decline, Dr. Aroda said.

Dr. Sattar agreed. Type 2 diabetes appears to help cause “fluid derangements” and abnormal hemodynamics that produces cardiac stress, changes in heart structure, and adverse remodeling of the heart, a process that “some call cardiomyopathy,” which is exacerbated by other pathologic forces that are also often present in these patients such as obesity and hypertension. SGLT2 inhibitors can help these patients by producing “reverse remodeling of the heart.”

“This process was neglected because for many years our focus was on ischemic heart disease in patients with type 2 diabetes. It was there in plain sight, but we were missing it,” explained Dr. Sattar. Having agents from the SGLT2 inhibitor class “has allowed us to better understand this mechanism.”

The SGLT2 inhibitors are “absolutely the driving reason” why the diabetes–heart failure link has become so important, said Dr. Inzucchi. Having drugs that reduce heart failure risk provided clinicians with a tool that has “changed our mindset.”

“Heart failure prevention has been largely neglected in patients with type 2 diabetes. Reprioritizing heart failure prevention to first and foremost among patients with type 2 diabetes is long overdue,” commented Gregg C. Fonarow, MD, professor and chief of cardiology at the University of California, Los Angeles.
 

Clinicians don’t like risk scores

Will systematic screening for heart failure risk in selected patients with type 2 diabetes take hold, and with it expanded and better-targeted use of SGLT2 inhibitors?

“I hope so,” said Dr. Kosiborod, but one challenge is that “for the most part clinicians don’t like using risk scores.” Only a few have ever been widely incorporated into practice; mostly they become tools for research. Plus, SGLT2 inhibitor uptake has in general been slow to catch on, which Dr. Kosiborod blames primarily on clinical inertia, a pervasive issue that has also hampered optimal use of drugs as commonplace as statins, ACE inhibitors, and angiotensin-receptor blockers.

“Given the avalanche of positive data, uptake of SGLT2 inhibitors will continue to improve and accelerate; but unfortunately, unless something dramatic happens we’ll likely see their continued underuse for several more years,” he predicted. “Designing better systems of care that prioritize prevention are absolutely needed to improve implementation of effective therapies, including SGLT2 inhibitors.”

Despite their underuse the SGLT2 inhibitor class has, in just 6 years since results from the EMPA-REG OUTCOME trial came out and launched the current treatment era, transformed thinking about the risk that heart failure poses to patients with type 2 diabetes and the need to manage this risk.

“I thank the SGLT2 inhibitors for raising awareness of heart failure risk in patients with diabetes,” and for giving clinicians a new way to mitigate this risk, said Dr. Cheng.

Dr. Berg has been a consultant to AstraZeneca, and received research grant support to his institution from AstraZeneca and Pfizer. Dr. Cheng has received personal fees from multiple pharmaceutical companies. Dr. Kosiborod has been an adviser and consultant to multiple pharmaceutical companies; has received research grants from AstraZeneca and Boehringer Ingelheim; and has received other research support from AstraZeneca. Dr. Pandey has been an adviser to Roche Diagnostics; has received nonfinancial support from Pfizer and Merck; and has received research support from Gilead Sciences, Myovista, and Applied Therapeutics. Dr. Sattar has received consulting honoraria from multiple pharmaceutical companies, and has received grant support from Boehringer Ingelheim, Roche Diagnostics, and Novartis. Dr. Aroda has been a consultant for several pharmaceutical companies; has a spouse employed with Janssen; and has received research support (institutional contracts) from multiple pharmaceutical companies. Dr. Fonarow has been a consultant to several pharmaceutical companies.

mzoler@mdedge.com

Agents that form the sodium-glucose cotransporter 2 inhibitor class – including canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – have show remarkably consistent cardiovascular efficacy and safety for treating patients with heart failure, chronic kidney disease, and higher-risk patients with type 2 diabetes.

But despite an essential role now established for drugs in the SGLT2 inhibitor class for patients with heart failure with reduced ejection fraction, progressive renal dysfunction, or – most recently – patients with heart failure with preserved ejection fraction, the scope may be less clear when using these agents in patients with type 2 diabetes because they fall across a broad spectrum of risk for cardiorenal disease.

“What makes patients with type 2 diabetes distinct from other patients in whom SGLT2 inhibitors have been studied, such as patients with heart failure, is that they have a much wider spectrum of risk. Low-risk patients with type 2 diabetes were not included in the SGLT2 inhibitor trials. Defining risk in patients with type 2 diabetes has the potential to inform prioritization” for treatment with an SGLT2 inhibitor, explained David D. Berg, MD, who has led one effort to develop risk scores that can risk-stratify patients with type 2 diabetes based on their vulnerability to incident heart failure and hospitalization for these episodes,

The hefty cost for these drugs, with retail prices that run over $6,000 annually for the most widely used and most potent agents in the class, has spurred researchers to try to find cost-effective ways to identify patients with type 2 diabetes who stand to benefit most from taking an SGLT2 inhibitor.
 

‘Cost must be considered’

“Cost must be considered, and at this point it’s probably more responsible on a societal level to advise using SGLT2 inhibitors mainly in patients [with type 2 diabetes] with compelling indications,” said Silvio Inzucchi, MD, professor and director of the Yale Medicine Diabetes Center in New Haven, Conn. Dr. Inzucchi added, however, that “I can easily foresee a day when these agents are considered foundational therapy for all patients with type 2 diabetes, after they go generic and cost is not a major issue. I’m starting to lean toward this very simplified approach, but the costs are prohibitive at this time.”

“If the SGLT2 inhibitors were available at a low cost, I’d argue that they should be used in all patients with type 2 diabetes who have no contraindications or tolerability issues; but we live in a world where they are not yet low cost,” agreed Mikhail N. Kosiborod, MD, a cardiologist and codirector of the Cardiometabolic Center of Excellence at Saint Luke’s Mid-America Heart Institute in Kansas City, Mo.

“We can’t give SGLT2 inhibitors to everyone with type 2 diabetes right now because that would be too costly; these agents are so expensive. You start by targeting the patients with the highest risk” for incident heart failure, said Ambarish Pandey, MD, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

The spotlight the SGLT2 inhibitor class has received, based on its unexpectedly potent efficacy in cutting rates of acute heart failure episodes in patients with type 2 diabetes, has also sharply raised the profile of this complication of type 2 diabetes, an outcome that until recently many clinicians had largely ignored, overshadowed by a focus on adverse outcomes from atherosclerotic cardiovascular disease such as MIs and strokes.

“Results from the SGLT2 inhibitor trials have reignited interest in the relationship between type 2 diabetes and heart failure and have started to shift the mindset of clinicians toward thinking about reducing both atherothrombotic risk and heart failure risk in patients with type 2 diabetes,” said Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston.

“Prior to the SGLT2 inhibitor trials, heart failure was on the radar of diabetes clinicians only as something to watch for as a potential side effect of certain glucose-lowering therapies. Now that there are therapies that can lower heart failure hospitalization, it’s made us think more about heart failure, how common it is in patients with type 2 diabetes, and what can we do to lower this risk,” commented Alice Y.Y. Cheng, MD, a diabetes specialist at the University of Toronto.
 

Banking on biomarkers

Risk scores for assessing the likelihood of people developing incident heart failure date back more than a decade. More recent efforts have focused on patients with type 2 diabetes, starting with scores that relied entirely on clinical markers of risk such as prior heart failure, established coronary artery disease, and chronic kidney disease. Reports of two of these validated scores appeared in 2019, one from a team led by Dr. Berg and associates in 2019, and a second score developed by Dr. Pandey and associates.

More recently, both research teams behind these two scores validated newer versions that further refined assessment of patients with diabetes by including biomarkers of incipient heart failure, such as N-terminal of the prohormone brain natriuretic peptide (NT-proBNP). The UT Southwestern group’s biomarker-based score relies on levels of NT-proBNP as well as on levels of high sensitivity troponin T (hsTnT) and C-reactive protein, plus ECG-based assessment of left ventricular hypertrophy to assess risk for incident heart failure. Developers reported in 2021 that this biomarker score could account for 74% (C-statistic) of the 5-year risk for heart failure among patients with diabetes.

The biomarker-based score devised by Dr. Berg and associates, relies on NT-proBNP, hsTnT, and a history of heart failure to predict the risk for a future hospitalization for heart failure. They reported in Diabetes Care that in validation testing this score accounted for 84% of the risk.

“I’m hopeful that both our original clinically-based risk score and our new biomarker-based score will be endorsed by professional society guidelines. The intent of the biomarker-based score is not to replace the clinical one,” Dr. Berg stressed in an interview. But he acknowledged that it uses biomarker values that currently are not routinely collected in U.S. practice. Biomarkers like NT-proBNP “are highly associated with future heart failure risk, but are not yet routinely assessed,” he said. Because of this, “widespread adoption of the [biomarker] risk tool will require some education.”

It may also require some sort of preliminary screening to determine the appropriateness of using it in a specific patient because of the relative expense of a test for NT-proBNP.

A Texas two-step process

“We can’t perform a [NT-proBNP] test on every patient with type 2 diabetes because cost is a huge barrier,” with a U.K. price of roughly £28 (about $40) per test, commented Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow. “NT-proBNP is the best biomarker by far to predict risk” for heart failure,” but “it’s too expensive. It’s not going to happen in everyone,” he said in an interview. He suggested taking a two-step approach to identify patients to test for NT-proBNP based on clinical measures like blood pressure, weight and height, lipid levels and renal function and the presence of suggestive symptoms like dyspnea, fatigue, and peripheral edema, an argument he recently spelled out in detail in an editorial he coauthored.

“More work is needed to define which patients would usefully have cardiac biomarkers measured,” Dr. Sattar wrote with his associate.

Two-step is the approach used in routine practice by clinicians at UT Southwestern Medical Center. “We screen all patients with type 2 diabetes and no diagnosed heart failure who are not already on an SGLT2 inhibitor” using their 2019 screening tool, called the WATCH-DM Risk score, said Dr. Pandey. Patients flagged at high risk by their clinical score receive an SGLT2 inhibitor (presuming no contraindications). The remaining patients with low or intermediate risk may then undergo biomarker-based assessment to find additional patients who warrant SGLT2 inhibitor treatment, he said in an interview.

Often, a record of the most important biomarker, NT-proBNP, is already in the patient’s record and less than a year old, in which case clinicians use that value. An NT-proBNP level of at least 125 pg/mL indicates increased risk in people with a body mass index of less than 30 kg/m², while for those with higher body mass indexes clinicians at Southwestern apply a threshold for higher risk of at least 100 pg/mL.

In addition to starting those patients on an SGLT2 inhibitor, the Southwestern protocol calls for intensified efforts at weight loss and improved fitness to further lower incident heart failure risk, and they are also considering targeting treatment with a glucagonlike peptide–1 receptor agonist to these patients as well. They have a research protocol in place, called WATCH-DM, that will prospectively assess the efficacy of this strategy.

Despite the cost, others also believe that the time is right for biomarker-based tests to boost access to the benefits that treatment with SGLT2 inhibitors can give patients with type 2 diabetes.

“In theory it’s reasonable” to use a risk score like the recent one reported by Dr. Berg and coauthors, said Vanita R. Aroda, MD, an endocrinologist and director of diabetes clinical research at Brigham and Women’s Hospital in Boston. “We need to pay attention to heart failure as an outcome and use risk stratification” to decide which patients with type 2 diabetes but without established cardiovascular disease warrant treatment with an SGLT2 inhibitor, she said in an interview. “Given the data, we need more concrete recommendations” from medical societies on how to reasonably use biomarkers and imaging to identify patients with type 2 diabetes who are at increased risk for heart failure and hence would benefit from treatment. “This should be of high interest to guidelines committees,” she added.

The earlier version of Dr. Berg’s score, based exclusively on clinical observations and conventional measures like estimated glomerular filtration rate and urinary creatinine to albumin ratio, had overlap with established criteria for starting treatment with an SGLT2 inhibitor, such as the presence of chronic kidney disease, she noted. “A biomarker-based score may provide the additional level of discrimination needed to characterize risk and potential benefit.”
 

Asymptomatic diabetic cardiomyopathy

Dr. Aroda and several coauthors recently published a review that describes a subset of patients with type 2 diabetes who might get picked up by intensified screening for heart failure risk: those with asymptomatic diabetic cardiomyopathy, a clinical state that they said represents patients with stage B heart failure based on the new Universal Definition and Classification of Heart Failure. Until recently, these patients with type 2 diabetes and asymptomatic cardiomyopathy have mostly gone unrecognized.

A recent report from Dr. Pandey and associates reviewed records from 2,900 U.S. patients with diabetes and no symptoms who had been included in any of three cohort studies and found echocardiographic evidence of early-stage cardiomyopathy in as many as two-thirds. In an editorial about this report, Dr. Aroda and coauthors called these patients a potential “window of opportunity for prevention and treatment of heart failure.”

“There is evidence of structural cardiac changes that progress through the stages of heart failure,” and starting treatment with an SGLT2 inhibitor during an earlier stage can potentially slow or prevent this progression and thereby limit future functional decline, Dr. Aroda said.

Dr. Sattar agreed. Type 2 diabetes appears to help cause “fluid derangements” and abnormal hemodynamics that produces cardiac stress, changes in heart structure, and adverse remodeling of the heart, a process that “some call cardiomyopathy,” which is exacerbated by other pathologic forces that are also often present in these patients such as obesity and hypertension. SGLT2 inhibitors can help these patients by producing “reverse remodeling of the heart.”

“This process was neglected because for many years our focus was on ischemic heart disease in patients with type 2 diabetes. It was there in plain sight, but we were missing it,” explained Dr. Sattar. Having agents from the SGLT2 inhibitor class “has allowed us to better understand this mechanism.”

The SGLT2 inhibitors are “absolutely the driving reason” why the diabetes–heart failure link has become so important, said Dr. Inzucchi. Having drugs that reduce heart failure risk provided clinicians with a tool that has “changed our mindset.”

“Heart failure prevention has been largely neglected in patients with type 2 diabetes. Reprioritizing heart failure prevention to first and foremost among patients with type 2 diabetes is long overdue,” commented Gregg C. Fonarow, MD, professor and chief of cardiology at the University of California, Los Angeles.
 

Clinicians don’t like risk scores

Will systematic screening for heart failure risk in selected patients with type 2 diabetes take hold, and with it expanded and better-targeted use of SGLT2 inhibitors?

“I hope so,” said Dr. Kosiborod, but one challenge is that “for the most part clinicians don’t like using risk scores.” Only a few have ever been widely incorporated into practice; mostly they become tools for research. Plus, SGLT2 inhibitor uptake has in general been slow to catch on, which Dr. Kosiborod blames primarily on clinical inertia, a pervasive issue that has also hampered optimal use of drugs as commonplace as statins, ACE inhibitors, and angiotensin-receptor blockers.

“Given the avalanche of positive data, uptake of SGLT2 inhibitors will continue to improve and accelerate; but unfortunately, unless something dramatic happens we’ll likely see their continued underuse for several more years,” he predicted. “Designing better systems of care that prioritize prevention are absolutely needed to improve implementation of effective therapies, including SGLT2 inhibitors.”

Despite their underuse the SGLT2 inhibitor class has, in just 6 years since results from the EMPA-REG OUTCOME trial came out and launched the current treatment era, transformed thinking about the risk that heart failure poses to patients with type 2 diabetes and the need to manage this risk.

“I thank the SGLT2 inhibitors for raising awareness of heart failure risk in patients with diabetes,” and for giving clinicians a new way to mitigate this risk, said Dr. Cheng.

Dr. Berg has been a consultant to AstraZeneca, and received research grant support to his institution from AstraZeneca and Pfizer. Dr. Cheng has received personal fees from multiple pharmaceutical companies. Dr. Kosiborod has been an adviser and consultant to multiple pharmaceutical companies; has received research grants from AstraZeneca and Boehringer Ingelheim; and has received other research support from AstraZeneca. Dr. Pandey has been an adviser to Roche Diagnostics; has received nonfinancial support from Pfizer and Merck; and has received research support from Gilead Sciences, Myovista, and Applied Therapeutics. Dr. Sattar has received consulting honoraria from multiple pharmaceutical companies, and has received grant support from Boehringer Ingelheim, Roche Diagnostics, and Novartis. Dr. Aroda has been a consultant for several pharmaceutical companies; has a spouse employed with Janssen; and has received research support (institutional contracts) from multiple pharmaceutical companies. Dr. Fonarow has been a consultant to several pharmaceutical companies.

mzoler@mdedge.com

Agents that form the sodium-glucose cotransporter 2 inhibitor class – including canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – have show remarkably consistent cardiovascular efficacy and safety for treating patients with heart failure, chronic kidney disease, and higher-risk patients with type 2 diabetes.

But despite an essential role now established for drugs in the SGLT2 inhibitor class for patients with heart failure with reduced ejection fraction, progressive renal dysfunction, or – most recently – patients with heart failure with preserved ejection fraction, the scope may be less clear when using these agents in patients with type 2 diabetes because they fall across a broad spectrum of risk for cardiorenal disease.

“What makes patients with type 2 diabetes distinct from other patients in whom SGLT2 inhibitors have been studied, such as patients with heart failure, is that they have a much wider spectrum of risk. Low-risk patients with type 2 diabetes were not included in the SGLT2 inhibitor trials. Defining risk in patients with type 2 diabetes has the potential to inform prioritization” for treatment with an SGLT2 inhibitor, explained David D. Berg, MD, who has led one effort to develop risk scores that can risk-stratify patients with type 2 diabetes based on their vulnerability to incident heart failure and hospitalization for these episodes,

The hefty cost for these drugs, with retail prices that run over $6,000 annually for the most widely used and most potent agents in the class, has spurred researchers to try to find cost-effective ways to identify patients with type 2 diabetes who stand to benefit most from taking an SGLT2 inhibitor.
 

‘Cost must be considered’

“Cost must be considered, and at this point it’s probably more responsible on a societal level to advise using SGLT2 inhibitors mainly in patients [with type 2 diabetes] with compelling indications,” said Silvio Inzucchi, MD, professor and director of the Yale Medicine Diabetes Center in New Haven, Conn. Dr. Inzucchi added, however, that “I can easily foresee a day when these agents are considered foundational therapy for all patients with type 2 diabetes, after they go generic and cost is not a major issue. I’m starting to lean toward this very simplified approach, but the costs are prohibitive at this time.”

“If the SGLT2 inhibitors were available at a low cost, I’d argue that they should be used in all patients with type 2 diabetes who have no contraindications or tolerability issues; but we live in a world where they are not yet low cost,” agreed Mikhail N. Kosiborod, MD, a cardiologist and codirector of the Cardiometabolic Center of Excellence at Saint Luke’s Mid-America Heart Institute in Kansas City, Mo.

“We can’t give SGLT2 inhibitors to everyone with type 2 diabetes right now because that would be too costly; these agents are so expensive. You start by targeting the patients with the highest risk” for incident heart failure, said Ambarish Pandey, MD, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

The spotlight the SGLT2 inhibitor class has received, based on its unexpectedly potent efficacy in cutting rates of acute heart failure episodes in patients with type 2 diabetes, has also sharply raised the profile of this complication of type 2 diabetes, an outcome that until recently many clinicians had largely ignored, overshadowed by a focus on adverse outcomes from atherosclerotic cardiovascular disease such as MIs and strokes.

“Results from the SGLT2 inhibitor trials have reignited interest in the relationship between type 2 diabetes and heart failure and have started to shift the mindset of clinicians toward thinking about reducing both atherothrombotic risk and heart failure risk in patients with type 2 diabetes,” said Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston.

“Prior to the SGLT2 inhibitor trials, heart failure was on the radar of diabetes clinicians only as something to watch for as a potential side effect of certain glucose-lowering therapies. Now that there are therapies that can lower heart failure hospitalization, it’s made us think more about heart failure, how common it is in patients with type 2 diabetes, and what can we do to lower this risk,” commented Alice Y.Y. Cheng, MD, a diabetes specialist at the University of Toronto.
 

Banking on biomarkers

Risk scores for assessing the likelihood of people developing incident heart failure date back more than a decade. More recent efforts have focused on patients with type 2 diabetes, starting with scores that relied entirely on clinical markers of risk such as prior heart failure, established coronary artery disease, and chronic kidney disease. Reports of two of these validated scores appeared in 2019, one from a team led by Dr. Berg and associates in 2019, and a second score developed by Dr. Pandey and associates.

More recently, both research teams behind these two scores validated newer versions that further refined assessment of patients with diabetes by including biomarkers of incipient heart failure, such as N-terminal of the prohormone brain natriuretic peptide (NT-proBNP). The UT Southwestern group’s biomarker-based score relies on levels of NT-proBNP as well as on levels of high sensitivity troponin T (hsTnT) and C-reactive protein, plus ECG-based assessment of left ventricular hypertrophy to assess risk for incident heart failure. Developers reported in 2021 that this biomarker score could account for 74% (C-statistic) of the 5-year risk for heart failure among patients with diabetes.

The biomarker-based score devised by Dr. Berg and associates, relies on NT-proBNP, hsTnT, and a history of heart failure to predict the risk for a future hospitalization for heart failure. They reported in Diabetes Care that in validation testing this score accounted for 84% of the risk.

“I’m hopeful that both our original clinically-based risk score and our new biomarker-based score will be endorsed by professional society guidelines. The intent of the biomarker-based score is not to replace the clinical one,” Dr. Berg stressed in an interview. But he acknowledged that it uses biomarker values that currently are not routinely collected in U.S. practice. Biomarkers like NT-proBNP “are highly associated with future heart failure risk, but are not yet routinely assessed,” he said. Because of this, “widespread adoption of the [biomarker] risk tool will require some education.”

It may also require some sort of preliminary screening to determine the appropriateness of using it in a specific patient because of the relative expense of a test for NT-proBNP.

A Texas two-step process

“We can’t perform a [NT-proBNP] test on every patient with type 2 diabetes because cost is a huge barrier,” with a U.K. price of roughly £28 (about $40) per test, commented Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow. “NT-proBNP is the best biomarker by far to predict risk” for heart failure,” but “it’s too expensive. It’s not going to happen in everyone,” he said in an interview. He suggested taking a two-step approach to identify patients to test for NT-proBNP based on clinical measures like blood pressure, weight and height, lipid levels and renal function and the presence of suggestive symptoms like dyspnea, fatigue, and peripheral edema, an argument he recently spelled out in detail in an editorial he coauthored.

“More work is needed to define which patients would usefully have cardiac biomarkers measured,” Dr. Sattar wrote with his associate.

Two-step is the approach used in routine practice by clinicians at UT Southwestern Medical Center. “We screen all patients with type 2 diabetes and no diagnosed heart failure who are not already on an SGLT2 inhibitor” using their 2019 screening tool, called the WATCH-DM Risk score, said Dr. Pandey. Patients flagged at high risk by their clinical score receive an SGLT2 inhibitor (presuming no contraindications). The remaining patients with low or intermediate risk may then undergo biomarker-based assessment to find additional patients who warrant SGLT2 inhibitor treatment, he said in an interview.

Often, a record of the most important biomarker, NT-proBNP, is already in the patient’s record and less than a year old, in which case clinicians use that value. An NT-proBNP level of at least 125 pg/mL indicates increased risk in people with a body mass index of less than 30 kg/m², while for those with higher body mass indexes clinicians at Southwestern apply a threshold for higher risk of at least 100 pg/mL.

In addition to starting those patients on an SGLT2 inhibitor, the Southwestern protocol calls for intensified efforts at weight loss and improved fitness to further lower incident heart failure risk, and they are also considering targeting treatment with a glucagonlike peptide–1 receptor agonist to these patients as well. They have a research protocol in place, called WATCH-DM, that will prospectively assess the efficacy of this strategy.

Despite the cost, others also believe that the time is right for biomarker-based tests to boost access to the benefits that treatment with SGLT2 inhibitors can give patients with type 2 diabetes.

“In theory it’s reasonable” to use a risk score like the recent one reported by Dr. Berg and coauthors, said Vanita R. Aroda, MD, an endocrinologist and director of diabetes clinical research at Brigham and Women’s Hospital in Boston. “We need to pay attention to heart failure as an outcome and use risk stratification” to decide which patients with type 2 diabetes but without established cardiovascular disease warrant treatment with an SGLT2 inhibitor, she said in an interview. “Given the data, we need more concrete recommendations” from medical societies on how to reasonably use biomarkers and imaging to identify patients with type 2 diabetes who are at increased risk for heart failure and hence would benefit from treatment. “This should be of high interest to guidelines committees,” she added.

The earlier version of Dr. Berg’s score, based exclusively on clinical observations and conventional measures like estimated glomerular filtration rate and urinary creatinine to albumin ratio, had overlap with established criteria for starting treatment with an SGLT2 inhibitor, such as the presence of chronic kidney disease, she noted. “A biomarker-based score may provide the additional level of discrimination needed to characterize risk and potential benefit.”
 

Asymptomatic diabetic cardiomyopathy

Dr. Aroda and several coauthors recently published a review that describes a subset of patients with type 2 diabetes who might get picked up by intensified screening for heart failure risk: those with asymptomatic diabetic cardiomyopathy, a clinical state that they said represents patients with stage B heart failure based on the new Universal Definition and Classification of Heart Failure. Until recently, these patients with type 2 diabetes and asymptomatic cardiomyopathy have mostly gone unrecognized.

A recent report from Dr. Pandey and associates reviewed records from 2,900 U.S. patients with diabetes and no symptoms who had been included in any of three cohort studies and found echocardiographic evidence of early-stage cardiomyopathy in as many as two-thirds. In an editorial about this report, Dr. Aroda and coauthors called these patients a potential “window of opportunity for prevention and treatment of heart failure.”

“There is evidence of structural cardiac changes that progress through the stages of heart failure,” and starting treatment with an SGLT2 inhibitor during an earlier stage can potentially slow or prevent this progression and thereby limit future functional decline, Dr. Aroda said.

Dr. Sattar agreed. Type 2 diabetes appears to help cause “fluid derangements” and abnormal hemodynamics that produces cardiac stress, changes in heart structure, and adverse remodeling of the heart, a process that “some call cardiomyopathy,” which is exacerbated by other pathologic forces that are also often present in these patients such as obesity and hypertension. SGLT2 inhibitors can help these patients by producing “reverse remodeling of the heart.”

“This process was neglected because for many years our focus was on ischemic heart disease in patients with type 2 diabetes. It was there in plain sight, but we were missing it,” explained Dr. Sattar. Having agents from the SGLT2 inhibitor class “has allowed us to better understand this mechanism.”

The SGLT2 inhibitors are “absolutely the driving reason” why the diabetes–heart failure link has become so important, said Dr. Inzucchi. Having drugs that reduce heart failure risk provided clinicians with a tool that has “changed our mindset.”

“Heart failure prevention has been largely neglected in patients with type 2 diabetes. Reprioritizing heart failure prevention to first and foremost among patients with type 2 diabetes is long overdue,” commented Gregg C. Fonarow, MD, professor and chief of cardiology at the University of California, Los Angeles.
 

Clinicians don’t like risk scores

Will systematic screening for heart failure risk in selected patients with type 2 diabetes take hold, and with it expanded and better-targeted use of SGLT2 inhibitors?

“I hope so,” said Dr. Kosiborod, but one challenge is that “for the most part clinicians don’t like using risk scores.” Only a few have ever been widely incorporated into practice; mostly they become tools for research. Plus, SGLT2 inhibitor uptake has in general been slow to catch on, which Dr. Kosiborod blames primarily on clinical inertia, a pervasive issue that has also hampered optimal use of drugs as commonplace as statins, ACE inhibitors, and angiotensin-receptor blockers.

“Given the avalanche of positive data, uptake of SGLT2 inhibitors will continue to improve and accelerate; but unfortunately, unless something dramatic happens we’ll likely see their continued underuse for several more years,” he predicted. “Designing better systems of care that prioritize prevention are absolutely needed to improve implementation of effective therapies, including SGLT2 inhibitors.”

Despite their underuse the SGLT2 inhibitor class has, in just 6 years since results from the EMPA-REG OUTCOME trial came out and launched the current treatment era, transformed thinking about the risk that heart failure poses to patients with type 2 diabetes and the need to manage this risk.

“I thank the SGLT2 inhibitors for raising awareness of heart failure risk in patients with diabetes,” and for giving clinicians a new way to mitigate this risk, said Dr. Cheng.

Dr. Berg has been a consultant to AstraZeneca, and received research grant support to his institution from AstraZeneca and Pfizer. Dr. Cheng has received personal fees from multiple pharmaceutical companies. Dr. Kosiborod has been an adviser and consultant to multiple pharmaceutical companies; has received research grants from AstraZeneca and Boehringer Ingelheim; and has received other research support from AstraZeneca. Dr. Pandey has been an adviser to Roche Diagnostics; has received nonfinancial support from Pfizer and Merck; and has received research support from Gilead Sciences, Myovista, and Applied Therapeutics. Dr. Sattar has received consulting honoraria from multiple pharmaceutical companies, and has received grant support from Boehringer Ingelheim, Roche Diagnostics, and Novartis. Dr. Aroda has been a consultant for several pharmaceutical companies; has a spouse employed with Janssen; and has received research support (institutional contracts) from multiple pharmaceutical companies. Dr. Fonarow has been a consultant to several pharmaceutical companies.

mzoler@mdedge.com

Obesity interventions would be more effective at preventing premature mortality if they focused less on weight loss and more on increased physical activity and improved cardiorespiratory fitness, a pair of researchers concluded in a recent review.

The authors promote a “weight-neutral approach to treating obesity-related health conditions,” which they say is “as or more effective than a weight-loss centric approach.”

One expert agrees. “The obsession with the bathroom scale as the primary determinant of treatment efficacy when managing obesity is just not right,” Robert Ross, PhD, said in an interview.

“It masks the tremendous health benefits of improved fitness regardless of obesity. If you increase fitness, you improve outcomes even when people don’t lose weight,” noted Dr. Ross, a researcher in the School of Kinesiology and Health Studies at Queen’s University in Kingston, Ontario, Canada.

However, this proposition reprises a long-standing gulf between two schools of thought on obesity intervention.

One indication of the divided sentiment came in another expert review, published just days later, that strongly calls for weight loss of at least 15% of starting body weight as the primary intervention goal for most patients with obesity and type 2 diabetes. (According to 2020 statistics from the U.S. Centers for Disease Control and Prevention, more than 60% of U.S. adults with diabetes are obese.)

However, some question whether it must be all one, or the other, when obesity management could instead combine these approaches and simultaneously promote weight loss, increased activity, and improved fitness.

“It only muddies the water to dichotomize this as either weight management or activity and physical fitness,” observed Scott Kahan, MD, an obesity specialist and director of the National Center for Weight and Wellness in Washington, D.C.
 

Weight-neutral ‘is the way to go’

“The most significant new information [in the review] is the direct comparison of the magnitude of mortality risk reduction associated with weight loss compared with increasing fitness, physical activity, or both,” said Glenn A. Gaesser, PhD, the first author of the new review and professor of exercise physiology at Arizona State University, Phoenix.

“The results are quite clear: Increasing fitness, physical activity, or both are associated with greater mortality reductions than intentional weight loss. We argue that a weight-neutral approach to treating obesity is the way to go.”

The data call “into question the widely perceived notion of ‘lose weight, live longer,’” resulting in a “paradigm shift,” Dr. Gaesser said in an interview.

“There are no downsides to exercise, but there are significant downsides to weight loss, especially when it is inevitably followed by weight regain, which gives rise to the undesirable ‘weight-loss futile cycle’,” he added.
 

No simple, single solutions

Dr. Kahan said, however, that comparison of the effects of weight loss with the effects of increased activity and fitness on mortality is inherently problematic.

“It’s hard to make definitive conclusions from observational studies,” he cautioned, noting that the data cited in the review of activity and fitness compared with weight loss are generally “estimations” that carry a “lot of cloudiness.”

Dr. Kahan also takes issue with the premise detailed in the review that targeting reduced weight and implementing healthful and evidence-based approaches to try to achieve it are bound to fail and have frequent adverse consequences.

“Managing weight in a reasonable, patient-centered, thoughtful way is a standard and central part of long-term health,” he said in an interview.

He did concede, however, that the U.S. weight-loss landscape is awash with hucksterism that takes advantage of many patients, and he cautioned against approaches that focus on weight loss at all costs and as a pathway to selling products.

“But staying focused on activity and not paying attention to healthy eating is extreme,” he said, reemphasizing that obesity management is not a simple intervention with a single solution.
 

Not the first time

This is not the first time that Dr. Gaesser, and others, have published articles promoting a pivot away from weight loss as the primary goal of obesity interventions. In 2015, Dr. Gaesser and colleagues published an evidence review that gave this recommendation for managing people with obesity: “We propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness.”

Dr. Gaesser’s latest review also acknowledges similar recommendations from others, including Dr. Ross, who said it’s nothing new to conclude that increased fitness and activity in the absence of weight loss is not failure.

“It’s something we’ve promoted for decades,” but “it’s not understood and acted on in clinical settings, and that’s unfortunate,” he said.

More than a decade ago, Dr. Ross and his coauthor wrote in a published review that “a monolithic focus on weight loss as the only determinant of success for strategies that aim to reduce obesity is not justified and, more importantly, eliminates opportunities to focus on lifestyle behaviors that are associated with benefit across a wide range of health outcomes.”

And an effective intervention that focuses on activity and fitness means that, at the least, patients should not gain weight, and they may lose weight as a side benefit, he stressed.

“We always advocate a balanced diet, so that people do not gain more weight.”

Dr. Ross also highlighted the usefulness of measuring fitness as an alternative to recording weight to track the response by patients with obesity to various interventions. Dr. Ross recommends nonexercise prediction equations for routine practice to easily estimate cardiorespiratory fitness, an approach detailed in a 2016 statement from the American Heart Association by a writing panel chaired by Dr. Ross.

The AHA statement notes that “not including cardiorespiratory fitness measurement in routine clinical practice fails to provide an optimal approach for stratifying patients according to risk.”

The AHA also advises that “routine estimation of cardiorespiratory fitness in clinical practice is no more difficult than measuring blood pressure,” and details ways of incorporating this into routine clinical assessment.

Dr. Gaesser and Dr. Kahan have reported no relevant financial relationships. Dr. Ross has been an advisor to the Canadian Sugar Institute.

A version of this article first appeared on Medscape.com.

Obesity interventions would be more effective at preventing premature mortality if they focused less on weight loss and more on increased physical activity and improved cardiorespiratory fitness, a pair of researchers concluded in a recent review.

The authors promote a “weight-neutral approach to treating obesity-related health conditions,” which they say is “as or more effective than a weight-loss centric approach.”

One expert agrees. “The obsession with the bathroom scale as the primary determinant of treatment efficacy when managing obesity is just not right,” Robert Ross, PhD, said in an interview.

“It masks the tremendous health benefits of improved fitness regardless of obesity. If you increase fitness, you improve outcomes even when people don’t lose weight,” noted Dr. Ross, a researcher in the School of Kinesiology and Health Studies at Queen’s University in Kingston, Ontario, Canada.

However, this proposition reprises a long-standing gulf between two schools of thought on obesity intervention.

One indication of the divided sentiment came in another expert review, published just days later, that strongly calls for weight loss of at least 15% of starting body weight as the primary intervention goal for most patients with obesity and type 2 diabetes. (According to 2020 statistics from the U.S. Centers for Disease Control and Prevention, more than 60% of U.S. adults with diabetes are obese.)

However, some question whether it must be all one, or the other, when obesity management could instead combine these approaches and simultaneously promote weight loss, increased activity, and improved fitness.

“It only muddies the water to dichotomize this as either weight management or activity and physical fitness,” observed Scott Kahan, MD, an obesity specialist and director of the National Center for Weight and Wellness in Washington, D.C.
 

Weight-neutral ‘is the way to go’

“The most significant new information [in the review] is the direct comparison of the magnitude of mortality risk reduction associated with weight loss compared with increasing fitness, physical activity, or both,” said Glenn A. Gaesser, PhD, the first author of the new review and professor of exercise physiology at Arizona State University, Phoenix.

“The results are quite clear: Increasing fitness, physical activity, or both are associated with greater mortality reductions than intentional weight loss. We argue that a weight-neutral approach to treating obesity is the way to go.”

The data call “into question the widely perceived notion of ‘lose weight, live longer,’” resulting in a “paradigm shift,” Dr. Gaesser said in an interview.

“There are no downsides to exercise, but there are significant downsides to weight loss, especially when it is inevitably followed by weight regain, which gives rise to the undesirable ‘weight-loss futile cycle’,” he added.
 

No simple, single solutions

Dr. Kahan said, however, that comparison of the effects of weight loss with the effects of increased activity and fitness on mortality is inherently problematic.

“It’s hard to make definitive conclusions from observational studies,” he cautioned, noting that the data cited in the review of activity and fitness compared with weight loss are generally “estimations” that carry a “lot of cloudiness.”

Dr. Kahan also takes issue with the premise detailed in the review that targeting reduced weight and implementing healthful and evidence-based approaches to try to achieve it are bound to fail and have frequent adverse consequences.

“Managing weight in a reasonable, patient-centered, thoughtful way is a standard and central part of long-term health,” he said in an interview.

He did concede, however, that the U.S. weight-loss landscape is awash with hucksterism that takes advantage of many patients, and he cautioned against approaches that focus on weight loss at all costs and as a pathway to selling products.

“But staying focused on activity and not paying attention to healthy eating is extreme,” he said, reemphasizing that obesity management is not a simple intervention with a single solution.
 

Not the first time

This is not the first time that Dr. Gaesser, and others, have published articles promoting a pivot away from weight loss as the primary goal of obesity interventions. In 2015, Dr. Gaesser and colleagues published an evidence review that gave this recommendation for managing people with obesity: “We propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness.”

Dr. Gaesser’s latest review also acknowledges similar recommendations from others, including Dr. Ross, who said it’s nothing new to conclude that increased fitness and activity in the absence of weight loss is not failure.

“It’s something we’ve promoted for decades,” but “it’s not understood and acted on in clinical settings, and that’s unfortunate,” he said.

More than a decade ago, Dr. Ross and his coauthor wrote in a published review that “a monolithic focus on weight loss as the only determinant of success for strategies that aim to reduce obesity is not justified and, more importantly, eliminates opportunities to focus on lifestyle behaviors that are associated with benefit across a wide range of health outcomes.”

And an effective intervention that focuses on activity and fitness means that, at the least, patients should not gain weight, and they may lose weight as a side benefit, he stressed.

“We always advocate a balanced diet, so that people do not gain more weight.”

Dr. Ross also highlighted the usefulness of measuring fitness as an alternative to recording weight to track the response by patients with obesity to various interventions. Dr. Ross recommends nonexercise prediction equations for routine practice to easily estimate cardiorespiratory fitness, an approach detailed in a 2016 statement from the American Heart Association by a writing panel chaired by Dr. Ross.

The AHA statement notes that “not including cardiorespiratory fitness measurement in routine clinical practice fails to provide an optimal approach for stratifying patients according to risk.”

The AHA also advises that “routine estimation of cardiorespiratory fitness in clinical practice is no more difficult than measuring blood pressure,” and details ways of incorporating this into routine clinical assessment.

Dr. Gaesser and Dr. Kahan have reported no relevant financial relationships. Dr. Ross has been an advisor to the Canadian Sugar Institute.

A version of this article first appeared on Medscape.com.

Obesity interventions would be more effective at preventing premature mortality if they focused less on weight loss and more on increased physical activity and improved cardiorespiratory fitness, a pair of researchers concluded in a recent review.

The authors promote a “weight-neutral approach to treating obesity-related health conditions,” which they say is “as or more effective than a weight-loss centric approach.”

One expert agrees. “The obsession with the bathroom scale as the primary determinant of treatment efficacy when managing obesity is just not right,” Robert Ross, PhD, said in an interview.

“It masks the tremendous health benefits of improved fitness regardless of obesity. If you increase fitness, you improve outcomes even when people don’t lose weight,” noted Dr. Ross, a researcher in the School of Kinesiology and Health Studies at Queen’s University in Kingston, Ontario, Canada.

However, this proposition reprises a long-standing gulf between two schools of thought on obesity intervention.

One indication of the divided sentiment came in another expert review, published just days later, that strongly calls for weight loss of at least 15% of starting body weight as the primary intervention goal for most patients with obesity and type 2 diabetes. (According to 2020 statistics from the U.S. Centers for Disease Control and Prevention, more than 60% of U.S. adults with diabetes are obese.)

However, some question whether it must be all one, or the other, when obesity management could instead combine these approaches and simultaneously promote weight loss, increased activity, and improved fitness.

“It only muddies the water to dichotomize this as either weight management or activity and physical fitness,” observed Scott Kahan, MD, an obesity specialist and director of the National Center for Weight and Wellness in Washington, D.C.
 

Weight-neutral ‘is the way to go’

“The most significant new information [in the review] is the direct comparison of the magnitude of mortality risk reduction associated with weight loss compared with increasing fitness, physical activity, or both,” said Glenn A. Gaesser, PhD, the first author of the new review and professor of exercise physiology at Arizona State University, Phoenix.

“The results are quite clear: Increasing fitness, physical activity, or both are associated with greater mortality reductions than intentional weight loss. We argue that a weight-neutral approach to treating obesity is the way to go.”

The data call “into question the widely perceived notion of ‘lose weight, live longer,’” resulting in a “paradigm shift,” Dr. Gaesser said in an interview.

“There are no downsides to exercise, but there are significant downsides to weight loss, especially when it is inevitably followed by weight regain, which gives rise to the undesirable ‘weight-loss futile cycle’,” he added.
 

No simple, single solutions

Dr. Kahan said, however, that comparison of the effects of weight loss with the effects of increased activity and fitness on mortality is inherently problematic.

“It’s hard to make definitive conclusions from observational studies,” he cautioned, noting that the data cited in the review of activity and fitness compared with weight loss are generally “estimations” that carry a “lot of cloudiness.”

Dr. Kahan also takes issue with the premise detailed in the review that targeting reduced weight and implementing healthful and evidence-based approaches to try to achieve it are bound to fail and have frequent adverse consequences.

“Managing weight in a reasonable, patient-centered, thoughtful way is a standard and central part of long-term health,” he said in an interview.

He did concede, however, that the U.S. weight-loss landscape is awash with hucksterism that takes advantage of many patients, and he cautioned against approaches that focus on weight loss at all costs and as a pathway to selling products.

“But staying focused on activity and not paying attention to healthy eating is extreme,” he said, reemphasizing that obesity management is not a simple intervention with a single solution.
 

Not the first time

This is not the first time that Dr. Gaesser, and others, have published articles promoting a pivot away from weight loss as the primary goal of obesity interventions. In 2015, Dr. Gaesser and colleagues published an evidence review that gave this recommendation for managing people with obesity: “We propose that the proxy for health improvements should not be weight loss but instead improvements in cardiometabolic parameters, functional status, and fitness.”

Dr. Gaesser’s latest review also acknowledges similar recommendations from others, including Dr. Ross, who said it’s nothing new to conclude that increased fitness and activity in the absence of weight loss is not failure.

“It’s something we’ve promoted for decades,” but “it’s not understood and acted on in clinical settings, and that’s unfortunate,” he said.

More than a decade ago, Dr. Ross and his coauthor wrote in a published review that “a monolithic focus on weight loss as the only determinant of success for strategies that aim to reduce obesity is not justified and, more importantly, eliminates opportunities to focus on lifestyle behaviors that are associated with benefit across a wide range of health outcomes.”

And an effective intervention that focuses on activity and fitness means that, at the least, patients should not gain weight, and they may lose weight as a side benefit, he stressed.

“We always advocate a balanced diet, so that people do not gain more weight.”

Dr. Ross also highlighted the usefulness of measuring fitness as an alternative to recording weight to track the response by patients with obesity to various interventions. Dr. Ross recommends nonexercise prediction equations for routine practice to easily estimate cardiorespiratory fitness, an approach detailed in a 2016 statement from the American Heart Association by a writing panel chaired by Dr. Ross.

The AHA statement notes that “not including cardiorespiratory fitness measurement in routine clinical practice fails to provide an optimal approach for stratifying patients according to risk.”

The AHA also advises that “routine estimation of cardiorespiratory fitness in clinical practice is no more difficult than measuring blood pressure,” and details ways of incorporating this into routine clinical assessment.

Dr. Gaesser and Dr. Kahan have reported no relevant financial relationships. Dr. Ross has been an advisor to the Canadian Sugar Institute.

A version of this article first appeared on Medscape.com.

Physicians could be doing a better job of counseling patients with obesity and overweight on weight loss and fertility. A study of 48 women seeking infertility care at a large academic center found that less than half received advice on weight loss from their primary ob.gyn. prior to referral for infertility treatment.

Patients are thinking about this – many attempt to lose weight independently of support from their health care providers, said lead study author Margaret R. O’Neill, MD, a resident at the University of Massachusetts Medical Center in Worcester. Dr. O’Neill discussed these results at the American Society of Reproductive Medicine’s 2021 meeting.

Nearly half of all U.S. women of reproductive age have overweight or obesity, with a body mass index of >25 kg/m². Menstrual irregularity, ovulatory dysfunction, reduced fecundity, and lower efficacy of infertility treatment are some of the consequences of obesity on fertility, said Dr. O’Neill. Obesity also affects the health of expectant mothers and fetuses, increasing the likelihood of gestational diabetes, preterm delivery, and preeclampsia, and increased incidence of fetal anomalies.

“Unfortunately, even though the prevalence of obesity has been increasing substantially in our country, there’s not excellent rates of this being addressed by physicians,” said Dr. O’Neill. BMI is often left out of documentation and rates of referrals to weight loss specialists are also low.

Conversations have been taking place about IVF centers instituting different BMI cutoffs for certain types of assisted reproductive technology, she noted.

Dr. O’Neill and her colleagues undertook a survey to see what advice community providers were dispensing about weight management on fertility.
 

Infertility specialists offer the most guidance

The prospective study included 48 nonpregnant women of reproductive age women presenting for IVF who needed an anesthesia consultation because of elevated BMI (> 35) prior to initiation of IVF. Mean age was 36 years and mean BMI was 38.5. More than 70% of the patients were White and they were predominantly English speakers.

All participants had attempted weight loss, including an attempt in the last year, and 93.8% reported trying to lose weight in the last year. On average, patients weighed about 20 pounds less than their heaviest adult weight. Nineteen percent of the participants were at their heaviest adult weight.

While 60% said they’d received weight loss/infertility counseling by any health care provider, just 41.7% reported that their primary ob.gyn. counseled them about weight loss before referring them for treatment. Infertility specialists seem to provide the most assistance: Nearly 70% of the respondents said they’ve been counseled by these providers.

Women with a higher-than-average BMI (39) were more likely to report a referral to weight loss counseling compared with women not referred (37.9, P = .2). 

Investigators also asked patients about their knowledge of obesity and its relationship to other health conditions. About 90% understood that infertility and excess weight were related. Overall, they were less sure about the link between obesity and still birth, breast cancer, and birth defects. Only 37% were able to identify a normal BMI range.
 

Avoiding a touchy subject

BMI is a highly sensitive area for many women, despite its detrimental effect on fertility, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.

“By the time their journey has led them to an infertility specialist, most women are very anxious to begin treatment,” said Dr. Trolice, who was not involved in the survey. These patients, however, could interpret any medical advice to achieve a more optimal BMI and healthier lifestyle as a negative judgment that could delay their goal of having a healthy child, he said.

Physicians in turn may avoid these conversations because they don’t want to encourage the ire of patients and/or risk a negative online rating review, he added.

Don’t say ‘just lose weight’

When asked what type of counseling works best, many said that nonspecific recommendations such as “you need to lose weight” or “exercise more” were the least helpful. Targeted advice such as “avoid eating at night and take walks every day,” works more effectively. “Any kind of referral to a bariatrics team or weight loss program was seen as helpful by patients,” said Dr. O’Neill.

Suggestions that considered the difficulty of this process, such as seeking therapy, were also helpful. “Patients appreciated empathy, compassion, and encouragement” from their physicians, she said.
 

The role of physicians in weight loss

Physicians can make a difference. Studies show that patients who received weight loss counseling were more likely to attempt weight loss and report clinically significant weight loss.

The American College of Obstetricians and Gynecologists and ASRM recommend counseling patients with overweight and obesity to lose weight before getting pregnant. A modest weight loss of 10% is associated with improved ovulatory function and higher pregnancy rates, said Dr. O’Neill.

“Appropriately, the infertility specialist should strongly recommend [that women who are obese] obtain a more optimal BMI prior to fertility treatment. While there is no guarantee of decreased infertility and decreased pregnancy complications following weight loss, a lower BMI improves outcomes,” said Dr. Trolice.

Future research should address the fertility outcomes of women who have been counseled by their providers to lose weight and the most effective method of counseling, noted Dr. O’Neill. “We have to find the best ways to address this at each fertility institution.”

The study had limited generalizability because of its narrow patient population and regional differences in access to insurance and weight loss specialists. COVID-19 also reduced the sample size, said Dr. O’Neill. She noted that patient perceptions might not equate with actual counseling delivered.

Dr. O’Neill and Dr. Trolice had no disclosures.

Physicians could be doing a better job of counseling patients with obesity and overweight on weight loss and fertility. A study of 48 women seeking infertility care at a large academic center found that less than half received advice on weight loss from their primary ob.gyn. prior to referral for infertility treatment.

Patients are thinking about this – many attempt to lose weight independently of support from their health care providers, said lead study author Margaret R. O’Neill, MD, a resident at the University of Massachusetts Medical Center in Worcester. Dr. O’Neill discussed these results at the American Society of Reproductive Medicine’s 2021 meeting.

Nearly half of all U.S. women of reproductive age have overweight or obesity, with a body mass index of >25 kg/m². Menstrual irregularity, ovulatory dysfunction, reduced fecundity, and lower efficacy of infertility treatment are some of the consequences of obesity on fertility, said Dr. O’Neill. Obesity also affects the health of expectant mothers and fetuses, increasing the likelihood of gestational diabetes, preterm delivery, and preeclampsia, and increased incidence of fetal anomalies.

“Unfortunately, even though the prevalence of obesity has been increasing substantially in our country, there’s not excellent rates of this being addressed by physicians,” said Dr. O’Neill. BMI is often left out of documentation and rates of referrals to weight loss specialists are also low.

Conversations have been taking place about IVF centers instituting different BMI cutoffs for certain types of assisted reproductive technology, she noted.

Dr. O’Neill and her colleagues undertook a survey to see what advice community providers were dispensing about weight management on fertility.
 

Infertility specialists offer the most guidance

The prospective study included 48 nonpregnant women of reproductive age women presenting for IVF who needed an anesthesia consultation because of elevated BMI (> 35) prior to initiation of IVF. Mean age was 36 years and mean BMI was 38.5. More than 70% of the patients were White and they were predominantly English speakers.

All participants had attempted weight loss, including an attempt in the last year, and 93.8% reported trying to lose weight in the last year. On average, patients weighed about 20 pounds less than their heaviest adult weight. Nineteen percent of the participants were at their heaviest adult weight.

While 60% said they’d received weight loss/infertility counseling by any health care provider, just 41.7% reported that their primary ob.gyn. counseled them about weight loss before referring them for treatment. Infertility specialists seem to provide the most assistance: Nearly 70% of the respondents said they’ve been counseled by these providers.

Women with a higher-than-average BMI (39) were more likely to report a referral to weight loss counseling compared with women not referred (37.9, P = .2). 

Investigators also asked patients about their knowledge of obesity and its relationship to other health conditions. About 90% understood that infertility and excess weight were related. Overall, they were less sure about the link between obesity and still birth, breast cancer, and birth defects. Only 37% were able to identify a normal BMI range.
 

Avoiding a touchy subject

BMI is a highly sensitive area for many women, despite its detrimental effect on fertility, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.

“By the time their journey has led them to an infertility specialist, most women are very anxious to begin treatment,” said Dr. Trolice, who was not involved in the survey. These patients, however, could interpret any medical advice to achieve a more optimal BMI and healthier lifestyle as a negative judgment that could delay their goal of having a healthy child, he said.

Physicians in turn may avoid these conversations because they don’t want to encourage the ire of patients and/or risk a negative online rating review, he added.

Don’t say ‘just lose weight’

When asked what type of counseling works best, many said that nonspecific recommendations such as “you need to lose weight” or “exercise more” were the least helpful. Targeted advice such as “avoid eating at night and take walks every day,” works more effectively. “Any kind of referral to a bariatrics team or weight loss program was seen as helpful by patients,” said Dr. O’Neill.

Suggestions that considered the difficulty of this process, such as seeking therapy, were also helpful. “Patients appreciated empathy, compassion, and encouragement” from their physicians, she said.
 

The role of physicians in weight loss

Physicians can make a difference. Studies show that patients who received weight loss counseling were more likely to attempt weight loss and report clinically significant weight loss.

The American College of Obstetricians and Gynecologists and ASRM recommend counseling patients with overweight and obesity to lose weight before getting pregnant. A modest weight loss of 10% is associated with improved ovulatory function and higher pregnancy rates, said Dr. O’Neill.

“Appropriately, the infertility specialist should strongly recommend [that women who are obese] obtain a more optimal BMI prior to fertility treatment. While there is no guarantee of decreased infertility and decreased pregnancy complications following weight loss, a lower BMI improves outcomes,” said Dr. Trolice.

Future research should address the fertility outcomes of women who have been counseled by their providers to lose weight and the most effective method of counseling, noted Dr. O’Neill. “We have to find the best ways to address this at each fertility institution.”

The study had limited generalizability because of its narrow patient population and regional differences in access to insurance and weight loss specialists. COVID-19 also reduced the sample size, said Dr. O’Neill. She noted that patient perceptions might not equate with actual counseling delivered.

Dr. O’Neill and Dr. Trolice had no disclosures.

Physicians could be doing a better job of counseling patients with obesity and overweight on weight loss and fertility. A study of 48 women seeking infertility care at a large academic center found that less than half received advice on weight loss from their primary ob.gyn. prior to referral for infertility treatment.

Patients are thinking about this – many attempt to lose weight independently of support from their health care providers, said lead study author Margaret R. O’Neill, MD, a resident at the University of Massachusetts Medical Center in Worcester. Dr. O’Neill discussed these results at the American Society of Reproductive Medicine’s 2021 meeting.

Nearly half of all U.S. women of reproductive age have overweight or obesity, with a body mass index of >25 kg/m². Menstrual irregularity, ovulatory dysfunction, reduced fecundity, and lower efficacy of infertility treatment are some of the consequences of obesity on fertility, said Dr. O’Neill. Obesity also affects the health of expectant mothers and fetuses, increasing the likelihood of gestational diabetes, preterm delivery, and preeclampsia, and increased incidence of fetal anomalies.

“Unfortunately, even though the prevalence of obesity has been increasing substantially in our country, there’s not excellent rates of this being addressed by physicians,” said Dr. O’Neill. BMI is often left out of documentation and rates of referrals to weight loss specialists are also low.

Conversations have been taking place about IVF centers instituting different BMI cutoffs for certain types of assisted reproductive technology, she noted.

Dr. O’Neill and her colleagues undertook a survey to see what advice community providers were dispensing about weight management on fertility.
 

Infertility specialists offer the most guidance

The prospective study included 48 nonpregnant women of reproductive age women presenting for IVF who needed an anesthesia consultation because of elevated BMI (> 35) prior to initiation of IVF. Mean age was 36 years and mean BMI was 38.5. More than 70% of the patients were White and they were predominantly English speakers.

All participants had attempted weight loss, including an attempt in the last year, and 93.8% reported trying to lose weight in the last year. On average, patients weighed about 20 pounds less than their heaviest adult weight. Nineteen percent of the participants were at their heaviest adult weight.

While 60% said they’d received weight loss/infertility counseling by any health care provider, just 41.7% reported that their primary ob.gyn. counseled them about weight loss before referring them for treatment. Infertility specialists seem to provide the most assistance: Nearly 70% of the respondents said they’ve been counseled by these providers.

Women with a higher-than-average BMI (39) were more likely to report a referral to weight loss counseling compared with women not referred (37.9, P = .2). 

Investigators also asked patients about their knowledge of obesity and its relationship to other health conditions. About 90% understood that infertility and excess weight were related. Overall, they were less sure about the link between obesity and still birth, breast cancer, and birth defects. Only 37% were able to identify a normal BMI range.
 

Avoiding a touchy subject

BMI is a highly sensitive area for many women, despite its detrimental effect on fertility, Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida and director of the IVF Center in Orlando, said in an interview.

“By the time their journey has led them to an infertility specialist, most women are very anxious to begin treatment,” said Dr. Trolice, who was not involved in the survey. These patients, however, could interpret any medical advice to achieve a more optimal BMI and healthier lifestyle as a negative judgment that could delay their goal of having a healthy child, he said.

Physicians in turn may avoid these conversations because they don’t want to encourage the ire of patients and/or risk a negative online rating review, he added.

Don’t say ‘just lose weight’

When asked what type of counseling works best, many said that nonspecific recommendations such as “you need to lose weight” or “exercise more” were the least helpful. Targeted advice such as “avoid eating at night and take walks every day,” works more effectively. “Any kind of referral to a bariatrics team or weight loss program was seen as helpful by patients,” said Dr. O’Neill.

Suggestions that considered the difficulty of this process, such as seeking therapy, were also helpful. “Patients appreciated empathy, compassion, and encouragement” from their physicians, she said.
 

The role of physicians in weight loss

Physicians can make a difference. Studies show that patients who received weight loss counseling were more likely to attempt weight loss and report clinically significant weight loss.

The American College of Obstetricians and Gynecologists and ASRM recommend counseling patients with overweight and obesity to lose weight before getting pregnant. A modest weight loss of 10% is associated with improved ovulatory function and higher pregnancy rates, said Dr. O’Neill.

“Appropriately, the infertility specialist should strongly recommend [that women who are obese] obtain a more optimal BMI prior to fertility treatment. While there is no guarantee of decreased infertility and decreased pregnancy complications following weight loss, a lower BMI improves outcomes,” said Dr. Trolice.

Future research should address the fertility outcomes of women who have been counseled by their providers to lose weight and the most effective method of counseling, noted Dr. O’Neill. “We have to find the best ways to address this at each fertility institution.”

The study had limited generalizability because of its narrow patient population and regional differences in access to insurance and weight loss specialists. COVID-19 also reduced the sample size, said Dr. O’Neill. She noted that patient perceptions might not equate with actual counseling delivered.

Dr. O’Neill and Dr. Trolice had no disclosures.

It’s hard for people to completely escape a history of obesity, even when they later achieve a healthy weight.

American adults who once had obesity but later achieved and maintained a healthy body mass index (BMI) normalized some, but not all, of the excess clinical risk associated with obesity in a review of data collected from about 20,000 people during a series of eight NHANES surveys.

Maia P. Smith, MD, reported the findings at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

“For some conditions, such as hypertension and dyslipidemia, the recovery [following a sharp drop in BMI] appears to be total, while for other conditions, like diabetes, the recovery is probabilistic. Some recover, but some don’t,” explained Dr. Smith in an interview.

“Weight loss reverses all, or essentially all, of the damage done by obesity in some people, but does not cause full reversal of the harm and does not fully resolve [type 2] diabetes in many others,” added Dr. Smith, an epidemiologist in the Department of Public Health and Preventive Medicine at St. George’s University, Grenada.

“The fact that ... analyses comparing formerly obese people to normal weight populations demonstrated improvement in population mean levels of hypertension and dyslipidemia is remarkable,” commented Rebecca T. Emeny, PhD, an epidemiologist at the Dartmouth Institute of Health Policy and Clinical Practice in Lebanon, New Hampshire, who was not involved with Dr. Smith’s study.

“The observation that the individuals who were able to maintain normal weight after past obesity were still at greater risk for diabetes compared with the normal weight group speaks to the recent discussion of obesity as a metabolic disorder rather than a problem of calories in and calories out,” said Dr. Emeny in an interview.

She cited a recent article that proposed a carbohydrate-insulin model for obesity in place of an energy-balance model. This, however, is still somewhat contentious.

Dr. Emeny also cautioned that “the results of this study compare populations. The design and analysis do not allow for interpretation of individual risk resulting from changes in weight.”
 

Those who formerly had obesity can reverse hypertension, dyslipidemia

The study by Dr. Smith and associates used data collected in the National Health and Nutrition Examination Survey (NHANES), which is performed every 2 years by the U.S. Centers for Disease Control and Prevention.

They used data from eight consecutive surveys starting in 1999-2000 and continuing through 2013-2014, yielding data from nearly 40,000 adults who were at least 20 years old.

In addition to the 326 people who formerly had obesity at some time previously during their life (BMI ≥30 kg/m²) but now had a healthy BMI, and 6,235 who were consistently at a healthy BMI, they also included 13,710 people who currently had obesity. They dropped the remaining survey participants who did not fit into one of these three categories.

The participants who formerly had obesity averaged 54 years old, compared with a mean age of 48 years among those with current obesity and 41 years among those who currently had a healthy BMI (who had never had obesity). The results showed no differences by sex, but those who formerly had obesity had a much higher smoking prevalence.

The people who reported a healthy BMI (18.5-24.9 kg/m²) after previously having obesity had current prevalence rates of hypertension and dyslipidemia that were, respectively, 8% and 13% higher than the prevalence rates among adults who consistently maintained a healthy BMI – differences that were not significant.

In contrast, people who had current BMIs that indicated obesity had prevalence rates of hypertension and dyslipidemia that were each a significant threefold higher than those with a healthy BMI.

The 326 respondents who formerly had obesity but now were at a healthy BMI had a threefold higher prevalence of diabetes than did the 6,235 who consistently had maintained a healthy BMI. This was substantially less than the over sevenfold higher prevalence of diabetes among those who currently had obesity compared with those who always had a healthy BMI.

All these analyses were adjusted for the potential confounders of age, sex, smoking history, and ethnicity.
 

‘Quitting’ obesity better than current obesity

The finding that reaching a healthy BMI after a period of obesity could reverse some but not all risks associated with obesity is reminiscent of the effects of smoking, noted Dr. Smith.

“Never is better than ever, but quitting,” or dropping weight to reach a healthy BMI, “is better than current,” she concluded.

But Dr. Emeny said this interpretation, “while motivating and catchy, places emphasis on individual responsibility and choice rather than on social circumstances.”

Social effects “must be considered when evaluating population-level disparities in obesity-related cardiometabolic risk,” cautioned Dr. Emeny.

“’Quitting’ obesity is much more complicated than individual choice or ability.”

Dr. Smith also conceded that her analyses did not correct for the possible confounding effects that changes in diet or physical activity may have had on the observations.

“Neither diet nor physical activity has a well-known summary measure that we could have included as an adjuster,” she explained.

Dr. Smith and Dr. Emeny have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It’s hard for people to completely escape a history of obesity, even when they later achieve a healthy weight.

American adults who once had obesity but later achieved and maintained a healthy body mass index (BMI) normalized some, but not all, of the excess clinical risk associated with obesity in a review of data collected from about 20,000 people during a series of eight NHANES surveys.

Maia P. Smith, MD, reported the findings at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

“For some conditions, such as hypertension and dyslipidemia, the recovery [following a sharp drop in BMI] appears to be total, while for other conditions, like diabetes, the recovery is probabilistic. Some recover, but some don’t,” explained Dr. Smith in an interview.

“Weight loss reverses all, or essentially all, of the damage done by obesity in some people, but does not cause full reversal of the harm and does not fully resolve [type 2] diabetes in many others,” added Dr. Smith, an epidemiologist in the Department of Public Health and Preventive Medicine at St. George’s University, Grenada.

“The fact that ... analyses comparing formerly obese people to normal weight populations demonstrated improvement in population mean levels of hypertension and dyslipidemia is remarkable,” commented Rebecca T. Emeny, PhD, an epidemiologist at the Dartmouth Institute of Health Policy and Clinical Practice in Lebanon, New Hampshire, who was not involved with Dr. Smith’s study.

“The observation that the individuals who were able to maintain normal weight after past obesity were still at greater risk for diabetes compared with the normal weight group speaks to the recent discussion of obesity as a metabolic disorder rather than a problem of calories in and calories out,” said Dr. Emeny in an interview.

She cited a recent article that proposed a carbohydrate-insulin model for obesity in place of an energy-balance model. This, however, is still somewhat contentious.

Dr. Emeny also cautioned that “the results of this study compare populations. The design and analysis do not allow for interpretation of individual risk resulting from changes in weight.”
 

Those who formerly had obesity can reverse hypertension, dyslipidemia

The study by Dr. Smith and associates used data collected in the National Health and Nutrition Examination Survey (NHANES), which is performed every 2 years by the U.S. Centers for Disease Control and Prevention.

They used data from eight consecutive surveys starting in 1999-2000 and continuing through 2013-2014, yielding data from nearly 40,000 adults who were at least 20 years old.

In addition to the 326 people who formerly had obesity at some time previously during their life (BMI ≥30 kg/m²) but now had a healthy BMI, and 6,235 who were consistently at a healthy BMI, they also included 13,710 people who currently had obesity. They dropped the remaining survey participants who did not fit into one of these three categories.

The participants who formerly had obesity averaged 54 years old, compared with a mean age of 48 years among those with current obesity and 41 years among those who currently had a healthy BMI (who had never had obesity). The results showed no differences by sex, but those who formerly had obesity had a much higher smoking prevalence.

The people who reported a healthy BMI (18.5-24.9 kg/m²) after previously having obesity had current prevalence rates of hypertension and dyslipidemia that were, respectively, 8% and 13% higher than the prevalence rates among adults who consistently maintained a healthy BMI – differences that were not significant.

In contrast, people who had current BMIs that indicated obesity had prevalence rates of hypertension and dyslipidemia that were each a significant threefold higher than those with a healthy BMI.

The 326 respondents who formerly had obesity but now were at a healthy BMI had a threefold higher prevalence of diabetes than did the 6,235 who consistently had maintained a healthy BMI. This was substantially less than the over sevenfold higher prevalence of diabetes among those who currently had obesity compared with those who always had a healthy BMI.

All these analyses were adjusted for the potential confounders of age, sex, smoking history, and ethnicity.
 

‘Quitting’ obesity better than current obesity

The finding that reaching a healthy BMI after a period of obesity could reverse some but not all risks associated with obesity is reminiscent of the effects of smoking, noted Dr. Smith.

“Never is better than ever, but quitting,” or dropping weight to reach a healthy BMI, “is better than current,” she concluded.

But Dr. Emeny said this interpretation, “while motivating and catchy, places emphasis on individual responsibility and choice rather than on social circumstances.”

Social effects “must be considered when evaluating population-level disparities in obesity-related cardiometabolic risk,” cautioned Dr. Emeny.

“’Quitting’ obesity is much more complicated than individual choice or ability.”

Dr. Smith also conceded that her analyses did not correct for the possible confounding effects that changes in diet or physical activity may have had on the observations.

“Neither diet nor physical activity has a well-known summary measure that we could have included as an adjuster,” she explained.

Dr. Smith and Dr. Emeny have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It’s hard for people to completely escape a history of obesity, even when they later achieve a healthy weight.

American adults who once had obesity but later achieved and maintained a healthy body mass index (BMI) normalized some, but not all, of the excess clinical risk associated with obesity in a review of data collected from about 20,000 people during a series of eight NHANES surveys.

Maia P. Smith, MD, reported the findings at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

“For some conditions, such as hypertension and dyslipidemia, the recovery [following a sharp drop in BMI] appears to be total, while for other conditions, like diabetes, the recovery is probabilistic. Some recover, but some don’t,” explained Dr. Smith in an interview.

“Weight loss reverses all, or essentially all, of the damage done by obesity in some people, but does not cause full reversal of the harm and does not fully resolve [type 2] diabetes in many others,” added Dr. Smith, an epidemiologist in the Department of Public Health and Preventive Medicine at St. George’s University, Grenada.

“The fact that ... analyses comparing formerly obese people to normal weight populations demonstrated improvement in population mean levels of hypertension and dyslipidemia is remarkable,” commented Rebecca T. Emeny, PhD, an epidemiologist at the Dartmouth Institute of Health Policy and Clinical Practice in Lebanon, New Hampshire, who was not involved with Dr. Smith’s study.

“The observation that the individuals who were able to maintain normal weight after past obesity were still at greater risk for diabetes compared with the normal weight group speaks to the recent discussion of obesity as a metabolic disorder rather than a problem of calories in and calories out,” said Dr. Emeny in an interview.

She cited a recent article that proposed a carbohydrate-insulin model for obesity in place of an energy-balance model. This, however, is still somewhat contentious.

Dr. Emeny also cautioned that “the results of this study compare populations. The design and analysis do not allow for interpretation of individual risk resulting from changes in weight.”
 

Those who formerly had obesity can reverse hypertension, dyslipidemia

The study by Dr. Smith and associates used data collected in the National Health and Nutrition Examination Survey (NHANES), which is performed every 2 years by the U.S. Centers for Disease Control and Prevention.

They used data from eight consecutive surveys starting in 1999-2000 and continuing through 2013-2014, yielding data from nearly 40,000 adults who were at least 20 years old.

In addition to the 326 people who formerly had obesity at some time previously during their life (BMI ≥30 kg/m²) but now had a healthy BMI, and 6,235 who were consistently at a healthy BMI, they also included 13,710 people who currently had obesity. They dropped the remaining survey participants who did not fit into one of these three categories.

The participants who formerly had obesity averaged 54 years old, compared with a mean age of 48 years among those with current obesity and 41 years among those who currently had a healthy BMI (who had never had obesity). The results showed no differences by sex, but those who formerly had obesity had a much higher smoking prevalence.

The people who reported a healthy BMI (18.5-24.9 kg/m²) after previously having obesity had current prevalence rates of hypertension and dyslipidemia that were, respectively, 8% and 13% higher than the prevalence rates among adults who consistently maintained a healthy BMI – differences that were not significant.

In contrast, people who had current BMIs that indicated obesity had prevalence rates of hypertension and dyslipidemia that were each a significant threefold higher than those with a healthy BMI.

The 326 respondents who formerly had obesity but now were at a healthy BMI had a threefold higher prevalence of diabetes than did the 6,235 who consistently had maintained a healthy BMI. This was substantially less than the over sevenfold higher prevalence of diabetes among those who currently had obesity compared with those who always had a healthy BMI.

All these analyses were adjusted for the potential confounders of age, sex, smoking history, and ethnicity.
 

‘Quitting’ obesity better than current obesity

The finding that reaching a healthy BMI after a period of obesity could reverse some but not all risks associated with obesity is reminiscent of the effects of smoking, noted Dr. Smith.

“Never is better than ever, but quitting,” or dropping weight to reach a healthy BMI, “is better than current,” she concluded.

But Dr. Emeny said this interpretation, “while motivating and catchy, places emphasis on individual responsibility and choice rather than on social circumstances.”

Social effects “must be considered when evaluating population-level disparities in obesity-related cardiometabolic risk,” cautioned Dr. Emeny.

“’Quitting’ obesity is much more complicated than individual choice or ability.”

Dr. Smith also conceded that her analyses did not correct for the possible confounding effects that changes in diet or physical activity may have had on the observations.

“Neither diet nor physical activity has a well-known summary measure that we could have included as an adjuster,” she explained.

Dr. Smith and Dr. Emeny have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Five years out, sleeve gastrectomy had a lower risk of mortality, complications, and reinterventions than gastric bypass, but there was a higher risk of surgical revision, including conversion to another bariatric surgery, gastrectomy, or anastomotic revision, according to a new analysis.

herjua/Thinkstock

Sleeve gastrectomy has gained rapid popularity, and now represents 60% of all bariatric procedures. It has demonstrated good efficacy and short-term safety, it is easier to perform than laparoscopic Roux-en-Y gastric bypass, and it is a safe option for high-risk patients, authors led by Ryan Howard, MD, of University of Michigan, Ann Arbor, wrote in JAMA Surgery.

Still, there are few comparative data on the long-term efficacy of the two procedures. Randomized, controlled trials have conducted long-term follow-up, but their small size has made it difficult to detect differences in rare outcomes. Observational studies are limited by the potential for bias. A novel approach to limiting bias is instrumental variables analysis, which controls for possible confounding using a factor that impacts treatment choice, but not patient outcome, to control for possible confounders. Studies using this approach confirmed the superior safety profile of sleeve gastrectomy in the short term.

The current study’s authors, used that method to examined 5-year outcomes in a Medicare population, in which obesity and its complications are especially frequent. Partly because of that lack of data, the Medical Evidence Development and Coverage Committee has called for more data in older patients and in patients with disabilities.

The researchers analyzed data from 95,405 Medicare claims between 2012 and 2018, using state-level variation in sleeve gastrectomy as the instrumental variable.

At 5 years, sleeve gastrectomy was associated with a lower cumulative frequency of mortality (4.27%; 95% confidence interval, 4.25%-4.30% vs. 5.67%; 95% CI, 5.63%-5.69%]), complications (22.10%; 95% CI, 22.06%-22.13% vs. 29.03%; 95% CI, 28.99%-29.08%), and reintervention (25.23%; 95% CI, 25.19%-25.27% vs. 33.57%; 95% CI, 33.52%-33.63%). At 5 years, surgical revision was more common in the sleeve gastrectomy group (2.91%; 95% CI, 2.90%-2.93% vs. 1.46%; 95% CI, 1.45%-1.47%).

The sleeve gastrectomy group had lower odds of all-cause hospitalization at 1 year (adjusted hazard ratio, 0.83; 95% CI, 0.80-0.86) and 3 years (aHR, 0.94; 95% CI, 0.90-0.98), as well as emergency department use at 1 year (aHR, 0.87; 95% CI, 0.84-0.90) and 3 years (aHR, 0.93; 95% CI, 0.90-0.97). There was no significant difference between the two groups at 5 years with respect to either outcome.

The effort to understand long-term outcomes of these two procedures has been challenging because follow-up is often incomplete, and because reporting isn’t always standardized, according Anita P. Courcoulas, MD, MPH, and Bestoun Ahmed, MD, in an accompanying editorial in JAMA Surgery. They noted that the differences in mortality is a new finding and the difference in surgical revisions confirmed something often seen in clinical practice. “Overall, these novel methods, which creatively balance unmeasured factors, have succeeded in providing important incremental findings about the long-term comparative safety outcomes between bariatric procedures that will be helpful in clinical practice,” the editorial authors wrote.

The complications discussed in the study are also difficult to interpret, according to Ali Aminian, MD, who is a professor of surgery and director of Bariatric and Metabolic Institute at Cleveland Clinic. They may be related to the surgery, or they may be complications that accrue as patients age. “So that doesn’t mean those were surgical complications, but [the findings are] in line with the other literature that [gastric sleeve] may be safer than gastric bypass, but in a different cohort of patients,” said Dr. Aminian, who was asked to comment.

“I thought it validated that which many of us in clinical practice see on a day to day basis,” said Shanu Kothari, MD, chair of surgery at Prisma Health, and the current president of American Society for Bariatric and Metabolic Surgery. He pointed out that the study was limited by its reliance on administrative claims, which makes it impossible to know the reduction in weight and obesity-related comorbid conditions following the procedures, as well as factors driving individual decisions: A surgeon might offer sleeve to a patient at higher risk of complications, but a gastric bypass to someone with more comorbidities. “What we don’t know is how to interpret this 35,000-foot view of Medicare data to that conversation with the patient sitting right in front of you,” said Dr. Kothari.

The authors similarly cited the “lack of clinical granularity in administrative claims data” among study limitations, as well as how the use of instrumental variables may leave the findings less applicable to patients more strongly indicated for one procedure over the other.

“Longer-term randomized clinical trials and observational studies are warranted to confirm these findings,” the study authors concluded. “Understanding the risk profile of various bariatric operations may further help patients and surgeons make the most appropriate decisions regarding plans of care.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Some study authors and editorialists reported funding from various groups and institutions, such as the National Institutes of Health and the VA Ann Arbor Health System. Dr. Kothari and Dr. Aminian have no relevant financial disclosures.

Five years out, sleeve gastrectomy had a lower risk of mortality, complications, and reinterventions than gastric bypass, but there was a higher risk of surgical revision, including conversion to another bariatric surgery, gastrectomy, or anastomotic revision, according to a new analysis.

herjua/Thinkstock

Sleeve gastrectomy has gained rapid popularity, and now represents 60% of all bariatric procedures. It has demonstrated good efficacy and short-term safety, it is easier to perform than laparoscopic Roux-en-Y gastric bypass, and it is a safe option for high-risk patients, authors led by Ryan Howard, MD, of University of Michigan, Ann Arbor, wrote in JAMA Surgery.

Still, there are few comparative data on the long-term efficacy of the two procedures. Randomized, controlled trials have conducted long-term follow-up, but their small size has made it difficult to detect differences in rare outcomes. Observational studies are limited by the potential for bias. A novel approach to limiting bias is instrumental variables analysis, which controls for possible confounding using a factor that impacts treatment choice, but not patient outcome, to control for possible confounders. Studies using this approach confirmed the superior safety profile of sleeve gastrectomy in the short term.

The current study’s authors, used that method to examined 5-year outcomes in a Medicare population, in which obesity and its complications are especially frequent. Partly because of that lack of data, the Medical Evidence Development and Coverage Committee has called for more data in older patients and in patients with disabilities.

The researchers analyzed data from 95,405 Medicare claims between 2012 and 2018, using state-level variation in sleeve gastrectomy as the instrumental variable.

At 5 years, sleeve gastrectomy was associated with a lower cumulative frequency of mortality (4.27%; 95% confidence interval, 4.25%-4.30% vs. 5.67%; 95% CI, 5.63%-5.69%]), complications (22.10%; 95% CI, 22.06%-22.13% vs. 29.03%; 95% CI, 28.99%-29.08%), and reintervention (25.23%; 95% CI, 25.19%-25.27% vs. 33.57%; 95% CI, 33.52%-33.63%). At 5 years, surgical revision was more common in the sleeve gastrectomy group (2.91%; 95% CI, 2.90%-2.93% vs. 1.46%; 95% CI, 1.45%-1.47%).

The sleeve gastrectomy group had lower odds of all-cause hospitalization at 1 year (adjusted hazard ratio, 0.83; 95% CI, 0.80-0.86) and 3 years (aHR, 0.94; 95% CI, 0.90-0.98), as well as emergency department use at 1 year (aHR, 0.87; 95% CI, 0.84-0.90) and 3 years (aHR, 0.93; 95% CI, 0.90-0.97). There was no significant difference between the two groups at 5 years with respect to either outcome.

The effort to understand long-term outcomes of these two procedures has been challenging because follow-up is often incomplete, and because reporting isn’t always standardized, according Anita P. Courcoulas, MD, MPH, and Bestoun Ahmed, MD, in an accompanying editorial in JAMA Surgery. They noted that the differences in mortality is a new finding and the difference in surgical revisions confirmed something often seen in clinical practice. “Overall, these novel methods, which creatively balance unmeasured factors, have succeeded in providing important incremental findings about the long-term comparative safety outcomes between bariatric procedures that will be helpful in clinical practice,” the editorial authors wrote.

The complications discussed in the study are also difficult to interpret, according to Ali Aminian, MD, who is a professor of surgery and director of Bariatric and Metabolic Institute at Cleveland Clinic. They may be related to the surgery, or they may be complications that accrue as patients age. “So that doesn’t mean those were surgical complications, but [the findings are] in line with the other literature that [gastric sleeve] may be safer than gastric bypass, but in a different cohort of patients,” said Dr. Aminian, who was asked to comment.

“I thought it validated that which many of us in clinical practice see on a day to day basis,” said Shanu Kothari, MD, chair of surgery at Prisma Health, and the current president of American Society for Bariatric and Metabolic Surgery. He pointed out that the study was limited by its reliance on administrative claims, which makes it impossible to know the reduction in weight and obesity-related comorbid conditions following the procedures, as well as factors driving individual decisions: A surgeon might offer sleeve to a patient at higher risk of complications, but a gastric bypass to someone with more comorbidities. “What we don’t know is how to interpret this 35,000-foot view of Medicare data to that conversation with the patient sitting right in front of you,” said Dr. Kothari.

The authors similarly cited the “lack of clinical granularity in administrative claims data” among study limitations, as well as how the use of instrumental variables may leave the findings less applicable to patients more strongly indicated for one procedure over the other.

“Longer-term randomized clinical trials and observational studies are warranted to confirm these findings,” the study authors concluded. “Understanding the risk profile of various bariatric operations may further help patients and surgeons make the most appropriate decisions regarding plans of care.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Some study authors and editorialists reported funding from various groups and institutions, such as the National Institutes of Health and the VA Ann Arbor Health System. Dr. Kothari and Dr. Aminian have no relevant financial disclosures.

Five years out, sleeve gastrectomy had a lower risk of mortality, complications, and reinterventions than gastric bypass, but there was a higher risk of surgical revision, including conversion to another bariatric surgery, gastrectomy, or anastomotic revision, according to a new analysis.

herjua/Thinkstock

Sleeve gastrectomy has gained rapid popularity, and now represents 60% of all bariatric procedures. It has demonstrated good efficacy and short-term safety, it is easier to perform than laparoscopic Roux-en-Y gastric bypass, and it is a safe option for high-risk patients, authors led by Ryan Howard, MD, of University of Michigan, Ann Arbor, wrote in JAMA Surgery.

Still, there are few comparative data on the long-term efficacy of the two procedures. Randomized, controlled trials have conducted long-term follow-up, but their small size has made it difficult to detect differences in rare outcomes. Observational studies are limited by the potential for bias. A novel approach to limiting bias is instrumental variables analysis, which controls for possible confounding using a factor that impacts treatment choice, but not patient outcome, to control for possible confounders. Studies using this approach confirmed the superior safety profile of sleeve gastrectomy in the short term.

The current study’s authors, used that method to examined 5-year outcomes in a Medicare population, in which obesity and its complications are especially frequent. Partly because of that lack of data, the Medical Evidence Development and Coverage Committee has called for more data in older patients and in patients with disabilities.

The researchers analyzed data from 95,405 Medicare claims between 2012 and 2018, using state-level variation in sleeve gastrectomy as the instrumental variable.

At 5 years, sleeve gastrectomy was associated with a lower cumulative frequency of mortality (4.27%; 95% confidence interval, 4.25%-4.30% vs. 5.67%; 95% CI, 5.63%-5.69%]), complications (22.10%; 95% CI, 22.06%-22.13% vs. 29.03%; 95% CI, 28.99%-29.08%), and reintervention (25.23%; 95% CI, 25.19%-25.27% vs. 33.57%; 95% CI, 33.52%-33.63%). At 5 years, surgical revision was more common in the sleeve gastrectomy group (2.91%; 95% CI, 2.90%-2.93% vs. 1.46%; 95% CI, 1.45%-1.47%).

The sleeve gastrectomy group had lower odds of all-cause hospitalization at 1 year (adjusted hazard ratio, 0.83; 95% CI, 0.80-0.86) and 3 years (aHR, 0.94; 95% CI, 0.90-0.98), as well as emergency department use at 1 year (aHR, 0.87; 95% CI, 0.84-0.90) and 3 years (aHR, 0.93; 95% CI, 0.90-0.97). There was no significant difference between the two groups at 5 years with respect to either outcome.

The effort to understand long-term outcomes of these two procedures has been challenging because follow-up is often incomplete, and because reporting isn’t always standardized, according Anita P. Courcoulas, MD, MPH, and Bestoun Ahmed, MD, in an accompanying editorial in JAMA Surgery. They noted that the differences in mortality is a new finding and the difference in surgical revisions confirmed something often seen in clinical practice. “Overall, these novel methods, which creatively balance unmeasured factors, have succeeded in providing important incremental findings about the long-term comparative safety outcomes between bariatric procedures that will be helpful in clinical practice,” the editorial authors wrote.

The complications discussed in the study are also difficult to interpret, according to Ali Aminian, MD, who is a professor of surgery and director of Bariatric and Metabolic Institute at Cleveland Clinic. They may be related to the surgery, or they may be complications that accrue as patients age. “So that doesn’t mean those were surgical complications, but [the findings are] in line with the other literature that [gastric sleeve] may be safer than gastric bypass, but in a different cohort of patients,” said Dr. Aminian, who was asked to comment.

“I thought it validated that which many of us in clinical practice see on a day to day basis,” said Shanu Kothari, MD, chair of surgery at Prisma Health, and the current president of American Society for Bariatric and Metabolic Surgery. He pointed out that the study was limited by its reliance on administrative claims, which makes it impossible to know the reduction in weight and obesity-related comorbid conditions following the procedures, as well as factors driving individual decisions: A surgeon might offer sleeve to a patient at higher risk of complications, but a gastric bypass to someone with more comorbidities. “What we don’t know is how to interpret this 35,000-foot view of Medicare data to that conversation with the patient sitting right in front of you,” said Dr. Kothari.

The authors similarly cited the “lack of clinical granularity in administrative claims data” among study limitations, as well as how the use of instrumental variables may leave the findings less applicable to patients more strongly indicated for one procedure over the other.

“Longer-term randomized clinical trials and observational studies are warranted to confirm these findings,” the study authors concluded. “Understanding the risk profile of various bariatric operations may further help patients and surgeons make the most appropriate decisions regarding plans of care.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Some study authors and editorialists reported funding from various groups and institutions, such as the National Institutes of Health and the VA Ann Arbor Health System. Dr. Kothari and Dr. Aminian have no relevant financial disclosures.