Diabetes

For people living with type 2 diabetes mellitus (T2D), exogenous insulin, whether given early or later in T2D diagnosis, can provide many pharmacologically desirable effects. But it has always been clear, and is now more widely recognized, that insulin treatments are not completely risk-free for the patient. There are now newer, non-insulin therapy options that could be used, along with certain patient lifestyle changes in diet and activity levels, that have been shown to achieve desired glucose control—without the associated risks that insulin can bring. 

But is it possible to markedly reduce the need for insulin in some 90% of T2D patients and to reduce the doses in the others? Yes—if patients have sufficient beta-cell function and are willing to change their lifestyle. This mode of treatment has been slowly gaining momentum as of late in the medical community because of the benefits it ultimately provides for the patient. In my practice, I personally have done this by using an evidence-based approach that includes thinking inside a larger box. It is a 2-way street, and each should drive the other: the right drugs (in the right doses), and in the right patients.

Why avoid early insulin therapy?

Is the requirement of early insulin therapy in many or most patients a myth?

Yes. It resulted from “old logic,” which was to use insulin early to reduce glucotoxicity and lipotoxicity. The American Diabetes Association guidelines recommend that glycated hemoglobin (HbA1c) should not exceed 8.0% and consider a fasting blood glucose level >250 mg/dL as high, with a need to start insulin treatment right away; other guidelines recommend initiating insulin immediately in patients with HbA1c >9% and postprandial glucose 300 mg/dL. But this was at a time when oral agents were not as effective and took time to titrate or engender good control. We now have agents that are more effective and start working right away.

         However, the main problem in early insulin treatment is the significant risk of over-insulinization—a vicious cycle of insulin-caused increased appetite, hypoglycemia-resultant increased weight gain, insulin resistance (poorer control), increased circulating insulin, etc. Moreover, weight gain and individual hypoglycemic events can cause an increase in the risk of cardiovascular (CV) events.

I believe clinicians must start as early as possible in the natural history of T2D to prevent progressive beta-cell failure. Do not believe in “first-, second-, or third-line”; in other words, do not prioritize, so there is no competition between classes. The goal I have for my patients is to provide therapies that aim for the lowest HbA1c possible without hypoglycemia, provide the greatest CV benefit, and assist in weight reduction.

My protocol, “the egregious eleven,” involves using the least number of agents in combinations that treat the greatest number of mechanisms of hyperglycemia—without the use of sulfonylureas (which cause beta-cell apoptosis, hypoglycemia, and weight gain). Fortunately, newer agents, such as glucagon-like peptide 1 receptor agonist (GLP-1 RA)  and sodium-glucose cotransporter 1 (SGLT-2) inhibitors, work right away, cause weight reduction, and have side benefits of CV risk reduction—as well as preserve beta-cell function. Metformin remains a valuable agent and has its own potential side benefits, and bromocriptine-QR and pioglitazone have CV side benefits. So, there is really no need for early insulin in true T2D patients (ie, those that are non-ketosis prone and have sufficient beta-cell reserve).

Why reduce insulin in patients who are already on insulin?

Prior protocols resulted in 40%-50% of T2D patients being placed on insulin unnecessarily. As discussed, the side effects of insulin are many; they include weight gain, insulin resistance, hypoglycemia, and CV complications—all of which have been associated with a decline in quality of life.

What is your approach to reduce or eliminate insulin in those already on it (unnecessarily)?

First, I pick the right patient. Physicians should use sound clinical judgment to identify patients with likely residual beta-cell function. It is not just the “insulin-resistant patient," as 30%-50% of type 1 diabetes mellitus patients also have insulin resistance.

It needs to be a definite T2D patient: not ketosis prone, a family history T2D, no islet cell antibodies (if one has any concerns, check for them). They were often started on insulin in the emergency department with no ketosis and never received non-insulin therapy.

Patients need to be willing to commit to my strict, no-concentrated-sweets diet, to perform careful glucose monitoring, and to check their ketones. Patients should be willing to contact me if their sugar level is >250 mg/dL for 2 measurements in a row, while testing 4 times a day or using a continuous glucose-monitoring (CGM) device.

            First, estimate a patient’s “current insulin need” (CIN), or the dose they might be on if they had not been subject to over-insulinization (ie, if they had not been subject to the “vicious cycle” discussed above). I do this by taking their total basal and bolus insulin dose, then reducing it by ~25% as the patient changes to a no-concentrated-sweets diet with an additional up-to-25% dose reduction if the patient has been experiencing symptomatic or asymptomatic hypoglycemia.

Next, I reduce this CIN number by ~25% upon starting a rapid-acting subcutaneous GLP-1 RA (liraglutide or oral semaglutide) and reduce the CIN another 20% as they start the SGLT-2 inhibitor. If patients come into my office on <40 U/d, I stop insulin as I start a GLP-1 RA and an SGLT-2 inhibitor and have them monitor home glucose levels to assure reasonable results as they go off the insulin and on their new therapy.

 If patients come into my office on >40 U/d, they go home on a GLP-1 RA and an SGLT-2 inhibitor and ~30% of their presenting dose, apportioned between basal/bolus dosing based on when they are currently getting hypoglycemic.

The rapid initial reduction in their insulin doses, with initial adjustments in estimated insulin doses as needed based on home glucose monitoring, and rapid stabilization of glycemic levels by the effectiveness of these 2 agents give patients great motivation to keep up with the diet/program.

Then, as patients lose weight, they are told to report any glucose measurements <80 mg/dL, so that further reduction in insulin doses can be made. When patients achieve a new steady state of glycemia, weight, and GLP-1 RA and SGLT-2 inhibitor doses, you can add bromocriptine-QR, pioglitazone, and/or metformin as needed to allow for a further reduction of insulin. And, as you see the delayed effects of subsequently adding these new agents (eg, glucose <80 mg/dL), you can ultimately stop insulin when they get to <10-12 U/d. The process works very well, even in those starting on up to 300 units of insulin daily. Patients love the outcome and will greatly appreciate your care.

 Feel free to contact Dr. Schwartz at stschwar@gmail.com with any questions about his protocol or diet.

For people living with type 2 diabetes mellitus (T2D), exogenous insulin, whether given early or later in T2D diagnosis, can provide many pharmacologically desirable effects. But it has always been clear, and is now more widely recognized, that insulin treatments are not completely risk-free for the patient. There are now newer, non-insulin therapy options that could be used, along with certain patient lifestyle changes in diet and activity levels, that have been shown to achieve desired glucose control—without the associated risks that insulin can bring. 

But is it possible to markedly reduce the need for insulin in some 90% of T2D patients and to reduce the doses in the others? Yes—if patients have sufficient beta-cell function and are willing to change their lifestyle. This mode of treatment has been slowly gaining momentum as of late in the medical community because of the benefits it ultimately provides for the patient. In my practice, I personally have done this by using an evidence-based approach that includes thinking inside a larger box. It is a 2-way street, and each should drive the other: the right drugs (in the right doses), and in the right patients.

Why avoid early insulin therapy?

Is the requirement of early insulin therapy in many or most patients a myth?

Yes. It resulted from “old logic,” which was to use insulin early to reduce glucotoxicity and lipotoxicity. The American Diabetes Association guidelines recommend that glycated hemoglobin (HbA1c) should not exceed 8.0% and consider a fasting blood glucose level >250 mg/dL as high, with a need to start insulin treatment right away; other guidelines recommend initiating insulin immediately in patients with HbA1c >9% and postprandial glucose 300 mg/dL. But this was at a time when oral agents were not as effective and took time to titrate or engender good control. We now have agents that are more effective and start working right away.

         However, the main problem in early insulin treatment is the significant risk of over-insulinization—a vicious cycle of insulin-caused increased appetite, hypoglycemia-resultant increased weight gain, insulin resistance (poorer control), increased circulating insulin, etc. Moreover, weight gain and individual hypoglycemic events can cause an increase in the risk of cardiovascular (CV) events.

I believe clinicians must start as early as possible in the natural history of T2D to prevent progressive beta-cell failure. Do not believe in “first-, second-, or third-line”; in other words, do not prioritize, so there is no competition between classes. The goal I have for my patients is to provide therapies that aim for the lowest HbA1c possible without hypoglycemia, provide the greatest CV benefit, and assist in weight reduction.

My protocol, “the egregious eleven,” involves using the least number of agents in combinations that treat the greatest number of mechanisms of hyperglycemia—without the use of sulfonylureas (which cause beta-cell apoptosis, hypoglycemia, and weight gain). Fortunately, newer agents, such as glucagon-like peptide 1 receptor agonist (GLP-1 RA)  and sodium-glucose cotransporter 1 (SGLT-2) inhibitors, work right away, cause weight reduction, and have side benefits of CV risk reduction—as well as preserve beta-cell function. Metformin remains a valuable agent and has its own potential side benefits, and bromocriptine-QR and pioglitazone have CV side benefits. So, there is really no need for early insulin in true T2D patients (ie, those that are non-ketosis prone and have sufficient beta-cell reserve).

Why reduce insulin in patients who are already on insulin?

Prior protocols resulted in 40%-50% of T2D patients being placed on insulin unnecessarily. As discussed, the side effects of insulin are many; they include weight gain, insulin resistance, hypoglycemia, and CV complications—all of which have been associated with a decline in quality of life.

What is your approach to reduce or eliminate insulin in those already on it (unnecessarily)?

First, I pick the right patient. Physicians should use sound clinical judgment to identify patients with likely residual beta-cell function. It is not just the “insulin-resistant patient," as 30%-50% of type 1 diabetes mellitus patients also have insulin resistance.

It needs to be a definite T2D patient: not ketosis prone, a family history T2D, no islet cell antibodies (if one has any concerns, check for them). They were often started on insulin in the emergency department with no ketosis and never received non-insulin therapy.

Patients need to be willing to commit to my strict, no-concentrated-sweets diet, to perform careful glucose monitoring, and to check their ketones. Patients should be willing to contact me if their sugar level is >250 mg/dL for 2 measurements in a row, while testing 4 times a day or using a continuous glucose-monitoring (CGM) device.

            First, estimate a patient’s “current insulin need” (CIN), or the dose they might be on if they had not been subject to over-insulinization (ie, if they had not been subject to the “vicious cycle” discussed above). I do this by taking their total basal and bolus insulin dose, then reducing it by ~25% as the patient changes to a no-concentrated-sweets diet with an additional up-to-25% dose reduction if the patient has been experiencing symptomatic or asymptomatic hypoglycemia.

Next, I reduce this CIN number by ~25% upon starting a rapid-acting subcutaneous GLP-1 RA (liraglutide or oral semaglutide) and reduce the CIN another 20% as they start the SGLT-2 inhibitor. If patients come into my office on <40 U/d, I stop insulin as I start a GLP-1 RA and an SGLT-2 inhibitor and have them monitor home glucose levels to assure reasonable results as they go off the insulin and on their new therapy.

 If patients come into my office on >40 U/d, they go home on a GLP-1 RA and an SGLT-2 inhibitor and ~30% of their presenting dose, apportioned between basal/bolus dosing based on when they are currently getting hypoglycemic.

The rapid initial reduction in their insulin doses, with initial adjustments in estimated insulin doses as needed based on home glucose monitoring, and rapid stabilization of glycemic levels by the effectiveness of these 2 agents give patients great motivation to keep up with the diet/program.

Then, as patients lose weight, they are told to report any glucose measurements <80 mg/dL, so that further reduction in insulin doses can be made. When patients achieve a new steady state of glycemia, weight, and GLP-1 RA and SGLT-2 inhibitor doses, you can add bromocriptine-QR, pioglitazone, and/or metformin as needed to allow for a further reduction of insulin. And, as you see the delayed effects of subsequently adding these new agents (eg, glucose <80 mg/dL), you can ultimately stop insulin when they get to <10-12 U/d. The process works very well, even in those starting on up to 300 units of insulin daily. Patients love the outcome and will greatly appreciate your care.

 Feel free to contact Dr. Schwartz at stschwar@gmail.com with any questions about his protocol or diet.

For people living with type 2 diabetes mellitus (T2D), exogenous insulin, whether given early or later in T2D diagnosis, can provide many pharmacologically desirable effects. But it has always been clear, and is now more widely recognized, that insulin treatments are not completely risk-free for the patient. There are now newer, non-insulin therapy options that could be used, along with certain patient lifestyle changes in diet and activity levels, that have been shown to achieve desired glucose control—without the associated risks that insulin can bring. 

But is it possible to markedly reduce the need for insulin in some 90% of T2D patients and to reduce the doses in the others? Yes—if patients have sufficient beta-cell function and are willing to change their lifestyle. This mode of treatment has been slowly gaining momentum as of late in the medical community because of the benefits it ultimately provides for the patient. In my practice, I personally have done this by using an evidence-based approach that includes thinking inside a larger box. It is a 2-way street, and each should drive the other: the right drugs (in the right doses), and in the right patients.

Why avoid early insulin therapy?

Is the requirement of early insulin therapy in many or most patients a myth?

Yes. It resulted from “old logic,” which was to use insulin early to reduce glucotoxicity and lipotoxicity. The American Diabetes Association guidelines recommend that glycated hemoglobin (HbA1c) should not exceed 8.0% and consider a fasting blood glucose level >250 mg/dL as high, with a need to start insulin treatment right away; other guidelines recommend initiating insulin immediately in patients with HbA1c >9% and postprandial glucose 300 mg/dL. But this was at a time when oral agents were not as effective and took time to titrate or engender good control. We now have agents that are more effective and start working right away.

         However, the main problem in early insulin treatment is the significant risk of over-insulinization—a vicious cycle of insulin-caused increased appetite, hypoglycemia-resultant increased weight gain, insulin resistance (poorer control), increased circulating insulin, etc. Moreover, weight gain and individual hypoglycemic events can cause an increase in the risk of cardiovascular (CV) events.

I believe clinicians must start as early as possible in the natural history of T2D to prevent progressive beta-cell failure. Do not believe in “first-, second-, or third-line”; in other words, do not prioritize, so there is no competition between classes. The goal I have for my patients is to provide therapies that aim for the lowest HbA1c possible without hypoglycemia, provide the greatest CV benefit, and assist in weight reduction.

My protocol, “the egregious eleven,” involves using the least number of agents in combinations that treat the greatest number of mechanisms of hyperglycemia—without the use of sulfonylureas (which cause beta-cell apoptosis, hypoglycemia, and weight gain). Fortunately, newer agents, such as glucagon-like peptide 1 receptor agonist (GLP-1 RA)  and sodium-glucose cotransporter 1 (SGLT-2) inhibitors, work right away, cause weight reduction, and have side benefits of CV risk reduction—as well as preserve beta-cell function. Metformin remains a valuable agent and has its own potential side benefits, and bromocriptine-QR and pioglitazone have CV side benefits. So, there is really no need for early insulin in true T2D patients (ie, those that are non-ketosis prone and have sufficient beta-cell reserve).

Why reduce insulin in patients who are already on insulin?

Prior protocols resulted in 40%-50% of T2D patients being placed on insulin unnecessarily. As discussed, the side effects of insulin are many; they include weight gain, insulin resistance, hypoglycemia, and CV complications—all of which have been associated with a decline in quality of life.

What is your approach to reduce or eliminate insulin in those already on it (unnecessarily)?

First, I pick the right patient. Physicians should use sound clinical judgment to identify patients with likely residual beta-cell function. It is not just the “insulin-resistant patient," as 30%-50% of type 1 diabetes mellitus patients also have insulin resistance.

It needs to be a definite T2D patient: not ketosis prone, a family history T2D, no islet cell antibodies (if one has any concerns, check for them). They were often started on insulin in the emergency department with no ketosis and never received non-insulin therapy.

Patients need to be willing to commit to my strict, no-concentrated-sweets diet, to perform careful glucose monitoring, and to check their ketones. Patients should be willing to contact me if their sugar level is >250 mg/dL for 2 measurements in a row, while testing 4 times a day or using a continuous glucose-monitoring (CGM) device.

            First, estimate a patient’s “current insulin need” (CIN), or the dose they might be on if they had not been subject to over-insulinization (ie, if they had not been subject to the “vicious cycle” discussed above). I do this by taking their total basal and bolus insulin dose, then reducing it by ~25% as the patient changes to a no-concentrated-sweets diet with an additional up-to-25% dose reduction if the patient has been experiencing symptomatic or asymptomatic hypoglycemia.

Next, I reduce this CIN number by ~25% upon starting a rapid-acting subcutaneous GLP-1 RA (liraglutide or oral semaglutide) and reduce the CIN another 20% as they start the SGLT-2 inhibitor. If patients come into my office on <40 U/d, I stop insulin as I start a GLP-1 RA and an SGLT-2 inhibitor and have them monitor home glucose levels to assure reasonable results as they go off the insulin and on their new therapy.

 If patients come into my office on >40 U/d, they go home on a GLP-1 RA and an SGLT-2 inhibitor and ~30% of their presenting dose, apportioned between basal/bolus dosing based on when they are currently getting hypoglycemic.

The rapid initial reduction in their insulin doses, with initial adjustments in estimated insulin doses as needed based on home glucose monitoring, and rapid stabilization of glycemic levels by the effectiveness of these 2 agents give patients great motivation to keep up with the diet/program.

Then, as patients lose weight, they are told to report any glucose measurements <80 mg/dL, so that further reduction in insulin doses can be made. When patients achieve a new steady state of glycemia, weight, and GLP-1 RA and SGLT-2 inhibitor doses, you can add bromocriptine-QR, pioglitazone, and/or metformin as needed to allow for a further reduction of insulin. And, as you see the delayed effects of subsequently adding these new agents (eg, glucose <80 mg/dL), you can ultimately stop insulin when they get to <10-12 U/d. The process works very well, even in those starting on up to 300 units of insulin daily. Patients love the outcome and will greatly appreciate your care.

 Feel free to contact Dr. Schwartz at stschwar@gmail.com with any questions about his protocol or diet.

Fitbit users who took 10,700 steps a day had a 44% lower risk of developing type 2 diabetes than those who only took 6,000 steps a day, regardless of age, sex, or body mass index, in an almost 4-year study.

The protective effect of daily step count on type 2 diabetes risk remained after adjusting for smoking and sedentary time.

Taking more steps per day was also associated with less risk of developing type 2 diabetes in different subgroups of physical activity intensity.

“Our data shows the importance of moving your body every day to lower your risk of [type 2] diabetes,” said the lead author of the research, Andrew S. Perry, MD. The findings were published online in the Journal of Clinical Endocrinology & Metabolism.
 

Despite low baseline risk, benefit from increased physical activity

The study was conducted in more than 5,000 participants in the National Institutes of Health’s All of Us research program who had a median age of 51 and were generally overweight (median BMI 27.8 kg/m²). Three quarters were women and 89% were White.

It used an innovative approach in a real-world population, said Dr. Perry, of Vanderbilt University Medical Center in Nashville, Tenn.

The individuals in this cohort had relatively few risk factors, so it was not surprising that the incidence of type 2 diabetes overall was low (2%), the researchers note. “Yet, despite being low risk, we still detected a signal of benefit from increased” physical activity, Dr. Perry and colleagues write.

The individuals had a median of 16 very active minutes/day, which corresponds to 112 very active minutes/week (ie, less than the guideline-recommended 150 minutes of physical activity/week).

“These results indicate that amounts of physical activity are correlated with lower risk of [type 2] diabetes, regardless of the intensity level, and even at amounts less than current guidelines recommend,” the researchers summarize.
 

Physical activity tracked over close to 4 years

Prior studies of the relationship between physical activity and type 2 diabetes risk relied primarily on questionnaires that asked people about physical activity at one point in time.

The researchers aimed to examine this association over time, in a contemporary cohort of Fitbit users who participated in the All of Us program.

From 12,781 participants with Fitbit data between 2010 and 2021, they identified 5,677 individuals who were at least 18 years old and had linked electronic health record data, no diabetes at baseline, at least 15 days of Fitbit data in the initial monitoring period, and at least 180 days of follow-up.

The Fitbit counts steps, and it also uses an algorithm to quantify physical activity intensity as lightly active (1.5-3 metabolic equivalent task (METs), fairly active (3-6 METs), and very active (> 6 METs).

During a median 3.8-year follow-up, participants made a median of 7,924 steps/day and were “fairly active” for a median of 16 minutes/day.

They found 97 new cases of type 2 diabetes over a follow-up of 4 years in the dataset.

The predicted cumulative incidence of type 2 diabetes at 5 years was 0.8% for individuals who walked 13,245 steps/day (90th percentile) vs. 2.3% for those who walked 4,301 steps/day (10th percentile).

“We hope to study more diverse populations in future studies to confirm the generalizability of these findings,” Dr. Perry said.

This study received funding from the National Heart, Lung, and Blood Institute. Dr. Perry reports no relevant financial relationships. Disclosures for the other authors are listed with the original article.

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

Fitbit users who took 10,700 steps a day had a 44% lower risk of developing type 2 diabetes than those who only took 6,000 steps a day, regardless of age, sex, or body mass index, in an almost 4-year study.

The protective effect of daily step count on type 2 diabetes risk remained after adjusting for smoking and sedentary time.

Taking more steps per day was also associated with less risk of developing type 2 diabetes in different subgroups of physical activity intensity.

“Our data shows the importance of moving your body every day to lower your risk of [type 2] diabetes,” said the lead author of the research, Andrew S. Perry, MD. The findings were published online in the Journal of Clinical Endocrinology & Metabolism.
 

Despite low baseline risk, benefit from increased physical activity

The study was conducted in more than 5,000 participants in the National Institutes of Health’s All of Us research program who had a median age of 51 and were generally overweight (median BMI 27.8 kg/m²). Three quarters were women and 89% were White.

It used an innovative approach in a real-world population, said Dr. Perry, of Vanderbilt University Medical Center in Nashville, Tenn.

The individuals in this cohort had relatively few risk factors, so it was not surprising that the incidence of type 2 diabetes overall was low (2%), the researchers note. “Yet, despite being low risk, we still detected a signal of benefit from increased” physical activity, Dr. Perry and colleagues write.

The individuals had a median of 16 very active minutes/day, which corresponds to 112 very active minutes/week (ie, less than the guideline-recommended 150 minutes of physical activity/week).

“These results indicate that amounts of physical activity are correlated with lower risk of [type 2] diabetes, regardless of the intensity level, and even at amounts less than current guidelines recommend,” the researchers summarize.
 

Physical activity tracked over close to 4 years

Prior studies of the relationship between physical activity and type 2 diabetes risk relied primarily on questionnaires that asked people about physical activity at one point in time.

The researchers aimed to examine this association over time, in a contemporary cohort of Fitbit users who participated in the All of Us program.

From 12,781 participants with Fitbit data between 2010 and 2021, they identified 5,677 individuals who were at least 18 years old and had linked electronic health record data, no diabetes at baseline, at least 15 days of Fitbit data in the initial monitoring period, and at least 180 days of follow-up.

The Fitbit counts steps, and it also uses an algorithm to quantify physical activity intensity as lightly active (1.5-3 metabolic equivalent task (METs), fairly active (3-6 METs), and very active (> 6 METs).

During a median 3.8-year follow-up, participants made a median of 7,924 steps/day and were “fairly active” for a median of 16 minutes/day.

They found 97 new cases of type 2 diabetes over a follow-up of 4 years in the dataset.

The predicted cumulative incidence of type 2 diabetes at 5 years was 0.8% for individuals who walked 13,245 steps/day (90th percentile) vs. 2.3% for those who walked 4,301 steps/day (10th percentile).

“We hope to study more diverse populations in future studies to confirm the generalizability of these findings,” Dr. Perry said.

This study received funding from the National Heart, Lung, and Blood Institute. Dr. Perry reports no relevant financial relationships. Disclosures for the other authors are listed with the original article.

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

Fitbit users who took 10,700 steps a day had a 44% lower risk of developing type 2 diabetes than those who only took 6,000 steps a day, regardless of age, sex, or body mass index, in an almost 4-year study.

The protective effect of daily step count on type 2 diabetes risk remained after adjusting for smoking and sedentary time.

Taking more steps per day was also associated with less risk of developing type 2 diabetes in different subgroups of physical activity intensity.

“Our data shows the importance of moving your body every day to lower your risk of [type 2] diabetes,” said the lead author of the research, Andrew S. Perry, MD. The findings were published online in the Journal of Clinical Endocrinology & Metabolism.
 

Despite low baseline risk, benefit from increased physical activity

The study was conducted in more than 5,000 participants in the National Institutes of Health’s All of Us research program who had a median age of 51 and were generally overweight (median BMI 27.8 kg/m²). Three quarters were women and 89% were White.

It used an innovative approach in a real-world population, said Dr. Perry, of Vanderbilt University Medical Center in Nashville, Tenn.

The individuals in this cohort had relatively few risk factors, so it was not surprising that the incidence of type 2 diabetes overall was low (2%), the researchers note. “Yet, despite being low risk, we still detected a signal of benefit from increased” physical activity, Dr. Perry and colleagues write.

The individuals had a median of 16 very active minutes/day, which corresponds to 112 very active minutes/week (ie, less than the guideline-recommended 150 minutes of physical activity/week).

“These results indicate that amounts of physical activity are correlated with lower risk of [type 2] diabetes, regardless of the intensity level, and even at amounts less than current guidelines recommend,” the researchers summarize.
 

Physical activity tracked over close to 4 years

Prior studies of the relationship between physical activity and type 2 diabetes risk relied primarily on questionnaires that asked people about physical activity at one point in time.

The researchers aimed to examine this association over time, in a contemporary cohort of Fitbit users who participated in the All of Us program.

From 12,781 participants with Fitbit data between 2010 and 2021, they identified 5,677 individuals who were at least 18 years old and had linked electronic health record data, no diabetes at baseline, at least 15 days of Fitbit data in the initial monitoring period, and at least 180 days of follow-up.

The Fitbit counts steps, and it also uses an algorithm to quantify physical activity intensity as lightly active (1.5-3 metabolic equivalent task (METs), fairly active (3-6 METs), and very active (> 6 METs).

During a median 3.8-year follow-up, participants made a median of 7,924 steps/day and were “fairly active” for a median of 16 minutes/day.

They found 97 new cases of type 2 diabetes over a follow-up of 4 years in the dataset.

The predicted cumulative incidence of type 2 diabetes at 5 years was 0.8% for individuals who walked 13,245 steps/day (90th percentile) vs. 2.3% for those who walked 4,301 steps/day (10th percentile).

“We hope to study more diverse populations in future studies to confirm the generalizability of these findings,” Dr. Perry said.

This study received funding from the National Heart, Lung, and Blood Institute. Dr. Perry reports no relevant financial relationships. Disclosures for the other authors are listed with the original article.

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

At a routine doctor’s visit, a member of the clinic staff takes digital pictures of a patient’s retinas.

Within seconds, an artificial intelligence (AI) algorithm determines if the patient has diabetic retinopathy, a complication of diabetes that can lead to blindness.

If they do, the physician refers the patient to an eye care specialist for further evaluation and treatment.

This scene already is playing out in primary care clinics around the United States and in other countries, and it may become more common.

Health care systems intend to expand their use of AI to screen for diabetic retinopathy in 2023, and companies are developing more algorithms for this purpose.

In May, OSF HealthCare, a network of medical facilities headquartered in Peoria, Ill., piloted an AI system to diagnose diabetic retinopathy, a condition that affects an estimated 4 million Americans. In 2023, the health care system plans to expand the technology to 34 locations.

Meanwhile, the Food and Drug Administration in November approved a new AI system to diagnose diabetic retinopathy, making AEYE-DS from AEYE Health the third such product on the market.

Roomasa Channa, MD, a clinician-scientist with the McPherson Eye Research Institute at the University of Wisconsin–Madison, has studied the use of AI in teenage patients with diabetes. She said she soon plans to use AI screening in federally qualified health centers to screen adults with diabetes.

Dr. Channa welcomed the latest regulatory clearance and said she hopes another Food and Drug Administration–cleared algorithm product will improve accessibility to the technology.

“It is good to see more players in the field: We need this technology to be readily available and affordable,” she said in an interview.
 

A mixed reception

Responses from physicians to this type of AI have been mixed. Some worry, for instance, that the algorithms might be programmed with unrecognized biases that could lead them to less accurately interpret images from certain patient groups. Researchers should be on the lookout out for this possibility, Dr. Channa said.

“We need more real-world studies in different settings,” she said. “We also need to keep collecting data on AI performance post approval,” like investigators do for newly approved drugs.

The first AI system to diagnose diabetic retinopathy, IDx-DR, was approved by the FDA in 2018 and rolled out in retail clinics soon after. A second system, EyeArt, gained clearance by the agency in 2020.

Adding AI algorithms into primary care practice has changed how patients with diabetes can receive a screening. It also has introduced a new way for certain medical conditions to be diagnosed in primary care.

The American Medical Association in 2021 released a new CPT code to allow clinicians to bill government and private insurers for use of these services. CPT code 92229 refers to imaging of the retina to detect disease with an automated analysis and report at the point of care.
 

Meeting a need

Health care clinics in underserved areas often do not have eye care providers onsite to conduct recommended screening exams, so AI could help patients receive screening who otherwise would not get it, Dr. Channa said.

Dr. Channa and colleagues successfully used one AI system, IDx-DR, to screen children at a pediatric diabetes clinic. Over a year, screening rates jumped from 49% to 95%.

This technology “can potentially help us in decreasing disparities in care and focusing our efforts on patients with the most severe diseases,” she said.

OSF HealthCare recently obtained an approximately $1 million grant from drug company Regeneron to expand the use of AI-based screening for diabetic retinopathy, following a successful pilot. Regeneron markets a treatment for diabetic retinopathy.

Without an AI option, recommended eye screening for patients with diabetes often falls through the cracks, according to Mark Meeker, DO, vice president of community medicine at OSF. Primary care physicians may refer patients elsewhere for their annual retinopathy screening exam.

“That often doesn’t get completed because it’s another trip, another appointment, another time away from work,” Dr. Meeker said.

All patients with diabetes should have their eyes screened each year, but between one- to two-thirds of patients nationwide do not, he said.

A member of the clinic staff takes digital pictures of the retina, almost always through undilated pupils.

If the result is normal, the patient is scheduled for another follow-up screening in a year. If early signs of diabetic retinopathy are spotted, patients are referred to an eye care specialist.

After 7 months of the pilot program, OSF had screened about 350 patients. Approximately 20% had diabetic retinopathy, according to OSF.
 

‘A huge impact’

OSF has about 66,000 patients with diabetes. About two-thirds do not receive annual screening, Dr. Meeker estimated. “This can have a huge impact on the quality of life in the coming years for our diabetic patients. It’s pretty profound.”

Eye care specialists typically treat diabetic retinopathy with lasers, surgery, or medication. For primary care clinicians, however, AI screening for retinopathy is an opportunity to emphasize how important it is to manage the disease and what its consequences can be.

AI screening is “another tool for us to use to get patients more engaged in their own care,” Dr. Meeker said. “This is probably the biggest advance in AI affecting our day-to-day interaction with patients that we’ve seen in primary care.”
 

A business opportunity, too?

The IDx-DR platform OSF is using in its clinics is owned by the company Digital Diagnostics. OSF Ventures, an investment arm of OSF HealthCare, has invested in the company, the health care system announced in August.

Other companies have had their products used in practice. In 2019, for example, Eyenuk described how its EyeArt system had been used to screen thousands of patients in Germany and in Italy.

And in 2021, Eyenuk reported that its customer base in the United States had expanded to more than 25 locations. The company credited a Centers for Medicare & Medicaid Services plan to cover CPT code 92229 with supporting this growth.

Zack Dvey-Aharon, PhD, the CEO of AEYE Health, said the company was motivated to enter this space when regulators decided that AI could be used to diagnose a condition — not just as a tool to help doctors arrive at a diagnosis.

With proper training, a person can diagnose diabetic retinopathy relatively easily if the image of the retina is of excellent quality. If image is dark or blurry, however, it’s a different story.

AI has its advantages in this scenario, according to Dr. Dvey-Aharon. “For AI, those darker, more blurry images are actually highly readable with fantastic accuracy.”
 

More to come?

The possibilities of AI in analyzing retinal images are vast.

New research shows that AI may be able to detect Alzheimer’s disease or predict a person’s risk for heart attack and stroke based on snapshots of the retina.

The retina may also shed light on kidney disease, control of blood glucose and blood pressure, hepatobiliary disease, and coronary artery calcium, according to Eric J. Topol, MD, director of Scripps Research Translational Institute in La Jolla, Calif.

Beyond retinas, interpretation of electrocardiograms (ECGs) may be another frontier for AI in primary care. In one trial, an AI-enhanced ECG reading facilitated early diagnosis of low ejection fraction, and some doctors now receive these reports routinely, Dr. Topol wrote.

The potential value of AI in medicine “extends to virtually all forms of medical images that have been assessed to date,” Dr. Topol wrote on his “Ground Truths” Substack.

Although much of the focus has been on what AI can see, researchers also are exploring what AI can do with what it hears. Early research suggests that algorithms may be able to diagnose disease by analyzing patients’ voices.

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

At a routine doctor’s visit, a member of the clinic staff takes digital pictures of a patient’s retinas.

Within seconds, an artificial intelligence (AI) algorithm determines if the patient has diabetic retinopathy, a complication of diabetes that can lead to blindness.

If they do, the physician refers the patient to an eye care specialist for further evaluation and treatment.

This scene already is playing out in primary care clinics around the United States and in other countries, and it may become more common.

Health care systems intend to expand their use of AI to screen for diabetic retinopathy in 2023, and companies are developing more algorithms for this purpose.

In May, OSF HealthCare, a network of medical facilities headquartered in Peoria, Ill., piloted an AI system to diagnose diabetic retinopathy, a condition that affects an estimated 4 million Americans. In 2023, the health care system plans to expand the technology to 34 locations.

Meanwhile, the Food and Drug Administration in November approved a new AI system to diagnose diabetic retinopathy, making AEYE-DS from AEYE Health the third such product on the market.

Roomasa Channa, MD, a clinician-scientist with the McPherson Eye Research Institute at the University of Wisconsin–Madison, has studied the use of AI in teenage patients with diabetes. She said she soon plans to use AI screening in federally qualified health centers to screen adults with diabetes.

Dr. Channa welcomed the latest regulatory clearance and said she hopes another Food and Drug Administration–cleared algorithm product will improve accessibility to the technology.

“It is good to see more players in the field: We need this technology to be readily available and affordable,” she said in an interview.
 

A mixed reception

Responses from physicians to this type of AI have been mixed. Some worry, for instance, that the algorithms might be programmed with unrecognized biases that could lead them to less accurately interpret images from certain patient groups. Researchers should be on the lookout out for this possibility, Dr. Channa said.

“We need more real-world studies in different settings,” she said. “We also need to keep collecting data on AI performance post approval,” like investigators do for newly approved drugs.

The first AI system to diagnose diabetic retinopathy, IDx-DR, was approved by the FDA in 2018 and rolled out in retail clinics soon after. A second system, EyeArt, gained clearance by the agency in 2020.

Adding AI algorithms into primary care practice has changed how patients with diabetes can receive a screening. It also has introduced a new way for certain medical conditions to be diagnosed in primary care.

The American Medical Association in 2021 released a new CPT code to allow clinicians to bill government and private insurers for use of these services. CPT code 92229 refers to imaging of the retina to detect disease with an automated analysis and report at the point of care.
 

Meeting a need

Health care clinics in underserved areas often do not have eye care providers onsite to conduct recommended screening exams, so AI could help patients receive screening who otherwise would not get it, Dr. Channa said.

Dr. Channa and colleagues successfully used one AI system, IDx-DR, to screen children at a pediatric diabetes clinic. Over a year, screening rates jumped from 49% to 95%.

This technology “can potentially help us in decreasing disparities in care and focusing our efforts on patients with the most severe diseases,” she said.

OSF HealthCare recently obtained an approximately $1 million grant from drug company Regeneron to expand the use of AI-based screening for diabetic retinopathy, following a successful pilot. Regeneron markets a treatment for diabetic retinopathy.

Without an AI option, recommended eye screening for patients with diabetes often falls through the cracks, according to Mark Meeker, DO, vice president of community medicine at OSF. Primary care physicians may refer patients elsewhere for their annual retinopathy screening exam.

“That often doesn’t get completed because it’s another trip, another appointment, another time away from work,” Dr. Meeker said.

All patients with diabetes should have their eyes screened each year, but between one- to two-thirds of patients nationwide do not, he said.

A member of the clinic staff takes digital pictures of the retina, almost always through undilated pupils.

If the result is normal, the patient is scheduled for another follow-up screening in a year. If early signs of diabetic retinopathy are spotted, patients are referred to an eye care specialist.

After 7 months of the pilot program, OSF had screened about 350 patients. Approximately 20% had diabetic retinopathy, according to OSF.
 

‘A huge impact’

OSF has about 66,000 patients with diabetes. About two-thirds do not receive annual screening, Dr. Meeker estimated. “This can have a huge impact on the quality of life in the coming years for our diabetic patients. It’s pretty profound.”

Eye care specialists typically treat diabetic retinopathy with lasers, surgery, or medication. For primary care clinicians, however, AI screening for retinopathy is an opportunity to emphasize how important it is to manage the disease and what its consequences can be.

AI screening is “another tool for us to use to get patients more engaged in their own care,” Dr. Meeker said. “This is probably the biggest advance in AI affecting our day-to-day interaction with patients that we’ve seen in primary care.”
 

A business opportunity, too?

The IDx-DR platform OSF is using in its clinics is owned by the company Digital Diagnostics. OSF Ventures, an investment arm of OSF HealthCare, has invested in the company, the health care system announced in August.

Other companies have had their products used in practice. In 2019, for example, Eyenuk described how its EyeArt system had been used to screen thousands of patients in Germany and in Italy.

And in 2021, Eyenuk reported that its customer base in the United States had expanded to more than 25 locations. The company credited a Centers for Medicare & Medicaid Services plan to cover CPT code 92229 with supporting this growth.

Zack Dvey-Aharon, PhD, the CEO of AEYE Health, said the company was motivated to enter this space when regulators decided that AI could be used to diagnose a condition — not just as a tool to help doctors arrive at a diagnosis.

With proper training, a person can diagnose diabetic retinopathy relatively easily if the image of the retina is of excellent quality. If image is dark or blurry, however, it’s a different story.

AI has its advantages in this scenario, according to Dr. Dvey-Aharon. “For AI, those darker, more blurry images are actually highly readable with fantastic accuracy.”
 

More to come?

The possibilities of AI in analyzing retinal images are vast.

New research shows that AI may be able to detect Alzheimer’s disease or predict a person’s risk for heart attack and stroke based on snapshots of the retina.

The retina may also shed light on kidney disease, control of blood glucose and blood pressure, hepatobiliary disease, and coronary artery calcium, according to Eric J. Topol, MD, director of Scripps Research Translational Institute in La Jolla, Calif.

Beyond retinas, interpretation of electrocardiograms (ECGs) may be another frontier for AI in primary care. In one trial, an AI-enhanced ECG reading facilitated early diagnosis of low ejection fraction, and some doctors now receive these reports routinely, Dr. Topol wrote.

The potential value of AI in medicine “extends to virtually all forms of medical images that have been assessed to date,” Dr. Topol wrote on his “Ground Truths” Substack.

Although much of the focus has been on what AI can see, researchers also are exploring what AI can do with what it hears. Early research suggests that algorithms may be able to diagnose disease by analyzing patients’ voices.

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

At a routine doctor’s visit, a member of the clinic staff takes digital pictures of a patient’s retinas.

Within seconds, an artificial intelligence (AI) algorithm determines if the patient has diabetic retinopathy, a complication of diabetes that can lead to blindness.

If they do, the physician refers the patient to an eye care specialist for further evaluation and treatment.

This scene already is playing out in primary care clinics around the United States and in other countries, and it may become more common.

Health care systems intend to expand their use of AI to screen for diabetic retinopathy in 2023, and companies are developing more algorithms for this purpose.

In May, OSF HealthCare, a network of medical facilities headquartered in Peoria, Ill., piloted an AI system to diagnose diabetic retinopathy, a condition that affects an estimated 4 million Americans. In 2023, the health care system plans to expand the technology to 34 locations.

Meanwhile, the Food and Drug Administration in November approved a new AI system to diagnose diabetic retinopathy, making AEYE-DS from AEYE Health the third such product on the market.

Roomasa Channa, MD, a clinician-scientist with the McPherson Eye Research Institute at the University of Wisconsin–Madison, has studied the use of AI in teenage patients with diabetes. She said she soon plans to use AI screening in federally qualified health centers to screen adults with diabetes.

Dr. Channa welcomed the latest regulatory clearance and said she hopes another Food and Drug Administration–cleared algorithm product will improve accessibility to the technology.

“It is good to see more players in the field: We need this technology to be readily available and affordable,” she said in an interview.
 

A mixed reception

Responses from physicians to this type of AI have been mixed. Some worry, for instance, that the algorithms might be programmed with unrecognized biases that could lead them to less accurately interpret images from certain patient groups. Researchers should be on the lookout out for this possibility, Dr. Channa said.

“We need more real-world studies in different settings,” she said. “We also need to keep collecting data on AI performance post approval,” like investigators do for newly approved drugs.

The first AI system to diagnose diabetic retinopathy, IDx-DR, was approved by the FDA in 2018 and rolled out in retail clinics soon after. A second system, EyeArt, gained clearance by the agency in 2020.

Adding AI algorithms into primary care practice has changed how patients with diabetes can receive a screening. It also has introduced a new way for certain medical conditions to be diagnosed in primary care.

The American Medical Association in 2021 released a new CPT code to allow clinicians to bill government and private insurers for use of these services. CPT code 92229 refers to imaging of the retina to detect disease with an automated analysis and report at the point of care.
 

Meeting a need

Health care clinics in underserved areas often do not have eye care providers onsite to conduct recommended screening exams, so AI could help patients receive screening who otherwise would not get it, Dr. Channa said.

Dr. Channa and colleagues successfully used one AI system, IDx-DR, to screen children at a pediatric diabetes clinic. Over a year, screening rates jumped from 49% to 95%.

This technology “can potentially help us in decreasing disparities in care and focusing our efforts on patients with the most severe diseases,” she said.

OSF HealthCare recently obtained an approximately $1 million grant from drug company Regeneron to expand the use of AI-based screening for diabetic retinopathy, following a successful pilot. Regeneron markets a treatment for diabetic retinopathy.

Without an AI option, recommended eye screening for patients with diabetes often falls through the cracks, according to Mark Meeker, DO, vice president of community medicine at OSF. Primary care physicians may refer patients elsewhere for their annual retinopathy screening exam.

“That often doesn’t get completed because it’s another trip, another appointment, another time away from work,” Dr. Meeker said.

All patients with diabetes should have their eyes screened each year, but between one- to two-thirds of patients nationwide do not, he said.

A member of the clinic staff takes digital pictures of the retina, almost always through undilated pupils.

If the result is normal, the patient is scheduled for another follow-up screening in a year. If early signs of diabetic retinopathy are spotted, patients are referred to an eye care specialist.

After 7 months of the pilot program, OSF had screened about 350 patients. Approximately 20% had diabetic retinopathy, according to OSF.
 

‘A huge impact’

OSF has about 66,000 patients with diabetes. About two-thirds do not receive annual screening, Dr. Meeker estimated. “This can have a huge impact on the quality of life in the coming years for our diabetic patients. It’s pretty profound.”

Eye care specialists typically treat diabetic retinopathy with lasers, surgery, or medication. For primary care clinicians, however, AI screening for retinopathy is an opportunity to emphasize how important it is to manage the disease and what its consequences can be.

AI screening is “another tool for us to use to get patients more engaged in their own care,” Dr. Meeker said. “This is probably the biggest advance in AI affecting our day-to-day interaction with patients that we’ve seen in primary care.”
 

A business opportunity, too?

The IDx-DR platform OSF is using in its clinics is owned by the company Digital Diagnostics. OSF Ventures, an investment arm of OSF HealthCare, has invested in the company, the health care system announced in August.

Other companies have had their products used in practice. In 2019, for example, Eyenuk described how its EyeArt system had been used to screen thousands of patients in Germany and in Italy.

And in 2021, Eyenuk reported that its customer base in the United States had expanded to more than 25 locations. The company credited a Centers for Medicare & Medicaid Services plan to cover CPT code 92229 with supporting this growth.

Zack Dvey-Aharon, PhD, the CEO of AEYE Health, said the company was motivated to enter this space when regulators decided that AI could be used to diagnose a condition — not just as a tool to help doctors arrive at a diagnosis.

With proper training, a person can diagnose diabetic retinopathy relatively easily if the image of the retina is of excellent quality. If image is dark or blurry, however, it’s a different story.

AI has its advantages in this scenario, according to Dr. Dvey-Aharon. “For AI, those darker, more blurry images are actually highly readable with fantastic accuracy.”
 

More to come?

The possibilities of AI in analyzing retinal images are vast.

New research shows that AI may be able to detect Alzheimer’s disease or predict a person’s risk for heart attack and stroke based on snapshots of the retina.

The retina may also shed light on kidney disease, control of blood glucose and blood pressure, hepatobiliary disease, and coronary artery calcium, according to Eric J. Topol, MD, director of Scripps Research Translational Institute in La Jolla, Calif.

Beyond retinas, interpretation of electrocardiograms (ECGs) may be another frontier for AI in primary care. In one trial, an AI-enhanced ECG reading facilitated early diagnosis of low ejection fraction, and some doctors now receive these reports routinely, Dr. Topol wrote.

The potential value of AI in medicine “extends to virtually all forms of medical images that have been assessed to date,” Dr. Topol wrote on his “Ground Truths” Substack.

Although much of the focus has been on what AI can see, researchers also are exploring what AI can do with what it hears. Early research suggests that algorithms may be able to diagnose disease by analyzing patients’ voices.

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

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.

Importantly, “this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage” type 2 diabetes, the authors report.

Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which “suggests the possibility of remission for patients with longer duration” of diabetes, they note.

©Thinkstock

‘Excellent outcome’

Invited to comment, Amy E. Rothberg, MD, PhD, who was not involved with the research, agreed that the study indicates that intermittent fasting works for diabetes remission.

“We know that diabetes remission is possible with calorie restriction and subsequent weight loss, and intermittent fasting is just one of the many [dietary] approaches that may be suitable, appealing, and sustainable to some individuals, and usually results in calorie restriction and therefore weight loss,” she said.

The most studied types of intermittent fasting diets are alternate-day fasting, the 5:2 diet, and time-restricted consumption, Dr. Rothberg told this news organization.

This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).

After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%), compared with only 2.8% of the 36 patients in the control group.

At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%).

This was “an excellent outcome,” said Dr. Rothberg, professor of nutritional sciences, School of Public Health, University of Michigan, Ann Arbor, and a co-author of an international consensus statement that defined diabetes remission.

On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months. “The large amount of weight reduction is key to continuing to achieve diabetes remission,” she noted.

This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.

Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity).

This was a small study, Dr. Rothberg acknowledged. The researchers did not specify which specific antidiabetic drugs patients were taking, and they did not determine waist or hip circumference or assess lipids.

The diet was culturally sensitive, appropriate, and feasible in this Chinese population and would not be generalizable to non-Asians.

Nevertheless, a similar approach could be used in any population if the diet is tailored to the individual, according to Dr. Rothberg. Importantly, patients would need to receive guidance from a dietician to make sure their diet comprises all the necessary micronutrients, vitamins, and minerals on fasting days, and they would need to maintain a relatively balanced diet and not gorge themselves on feast days. 

“I think we should campaign widely about lifestyle approaches to achieve diabetes remission,” she urged.
 

72 patients with diabetes for an average of 6.6 years

“Despite a widespread public consensus that [type 2 diabetes] is irreversible and requires drug treatment escalation, there is some evidence of the possibility of remission,” Dr. Yang and colleagues write in their article.

They aimed to evaluate the effectiveness of intermittent fasting for diabetes remission and the durability of diabetes remission at 1 year.

Diabetes remission was defined having a stable A1c less than 6.5% for at least 3 months after discontinuing all antidiabetic medications, confirmed in at least annual A1c measurements (according to a 2021 consensus statement initiated by the American Diabetes Association).

Between 2019 and 2020, the researchers enrolled 72 participants aged 38-72 years who had had type 2 diabetes (duration 1 to 11 years) and a body mass index (BMI) of 19.1-30.4 kg/m². Patients were randomized 1:1 to the intermittent fasting group or control group.

Baseline characteristics were similar in both groups. Patients were a mean age of 53 years and roughly 60% were men. They had a mean BMI of 24 kg/m², a mean duration of diabetes of 6.6 years, and a mean A1c of 7.6%, and they were taking an average of 1.8 glucose-lowering medications.  

On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.

On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50%-65% of total energy intake from carbohydrates, 15%-20% from protein, and 20%-30% from fat, and had greater than or equal to 5 g fiber per serving.

Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.

The study received funding from the National Natural Science Foundation of China. The authors have reported no relevant financial disclosures.

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

In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.

Importantly, “this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage” type 2 diabetes, the authors report.

Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which “suggests the possibility of remission for patients with longer duration” of diabetes, they note.

©Thinkstock

‘Excellent outcome’

Invited to comment, Amy E. Rothberg, MD, PhD, who was not involved with the research, agreed that the study indicates that intermittent fasting works for diabetes remission.

“We know that diabetes remission is possible with calorie restriction and subsequent weight loss, and intermittent fasting is just one of the many [dietary] approaches that may be suitable, appealing, and sustainable to some individuals, and usually results in calorie restriction and therefore weight loss,” she said.

The most studied types of intermittent fasting diets are alternate-day fasting, the 5:2 diet, and time-restricted consumption, Dr. Rothberg told this news organization.

This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).

After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%), compared with only 2.8% of the 36 patients in the control group.

At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%).

This was “an excellent outcome,” said Dr. Rothberg, professor of nutritional sciences, School of Public Health, University of Michigan, Ann Arbor, and a co-author of an international consensus statement that defined diabetes remission.

On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months. “The large amount of weight reduction is key to continuing to achieve diabetes remission,” she noted.

This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.

Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity).

This was a small study, Dr. Rothberg acknowledged. The researchers did not specify which specific antidiabetic drugs patients were taking, and they did not determine waist or hip circumference or assess lipids.

The diet was culturally sensitive, appropriate, and feasible in this Chinese population and would not be generalizable to non-Asians.

Nevertheless, a similar approach could be used in any population if the diet is tailored to the individual, according to Dr. Rothberg. Importantly, patients would need to receive guidance from a dietician to make sure their diet comprises all the necessary micronutrients, vitamins, and minerals on fasting days, and they would need to maintain a relatively balanced diet and not gorge themselves on feast days. 

“I think we should campaign widely about lifestyle approaches to achieve diabetes remission,” she urged.
 

72 patients with diabetes for an average of 6.6 years

“Despite a widespread public consensus that [type 2 diabetes] is irreversible and requires drug treatment escalation, there is some evidence of the possibility of remission,” Dr. Yang and colleagues write in their article.

They aimed to evaluate the effectiveness of intermittent fasting for diabetes remission and the durability of diabetes remission at 1 year.

Diabetes remission was defined having a stable A1c less than 6.5% for at least 3 months after discontinuing all antidiabetic medications, confirmed in at least annual A1c measurements (according to a 2021 consensus statement initiated by the American Diabetes Association).

Between 2019 and 2020, the researchers enrolled 72 participants aged 38-72 years who had had type 2 diabetes (duration 1 to 11 years) and a body mass index (BMI) of 19.1-30.4 kg/m². Patients were randomized 1:1 to the intermittent fasting group or control group.

Baseline characteristics were similar in both groups. Patients were a mean age of 53 years and roughly 60% were men. They had a mean BMI of 24 kg/m², a mean duration of diabetes of 6.6 years, and a mean A1c of 7.6%, and they were taking an average of 1.8 glucose-lowering medications.  

On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.

On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50%-65% of total energy intake from carbohydrates, 15%-20% from protein, and 20%-30% from fat, and had greater than or equal to 5 g fiber per serving.

Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.

The study received funding from the National Natural Science Foundation of China. The authors have reported no relevant financial disclosures.

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

In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.

Importantly, “this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage” type 2 diabetes, the authors report.

Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which “suggests the possibility of remission for patients with longer duration” of diabetes, they note.

©Thinkstock

‘Excellent outcome’

Invited to comment, Amy E. Rothberg, MD, PhD, who was not involved with the research, agreed that the study indicates that intermittent fasting works for diabetes remission.

“We know that diabetes remission is possible with calorie restriction and subsequent weight loss, and intermittent fasting is just one of the many [dietary] approaches that may be suitable, appealing, and sustainable to some individuals, and usually results in calorie restriction and therefore weight loss,” she said.

The most studied types of intermittent fasting diets are alternate-day fasting, the 5:2 diet, and time-restricted consumption, Dr. Rothberg told this news organization.

This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).

After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%), compared with only 2.8% of the 36 patients in the control group.

At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%).

This was “an excellent outcome,” said Dr. Rothberg, professor of nutritional sciences, School of Public Health, University of Michigan, Ann Arbor, and a co-author of an international consensus statement that defined diabetes remission.

On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months. “The large amount of weight reduction is key to continuing to achieve diabetes remission,” she noted.

This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.

Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity).

This was a small study, Dr. Rothberg acknowledged. The researchers did not specify which specific antidiabetic drugs patients were taking, and they did not determine waist or hip circumference or assess lipids.

The diet was culturally sensitive, appropriate, and feasible in this Chinese population and would not be generalizable to non-Asians.

Nevertheless, a similar approach could be used in any population if the diet is tailored to the individual, according to Dr. Rothberg. Importantly, patients would need to receive guidance from a dietician to make sure their diet comprises all the necessary micronutrients, vitamins, and minerals on fasting days, and they would need to maintain a relatively balanced diet and not gorge themselves on feast days. 

“I think we should campaign widely about lifestyle approaches to achieve diabetes remission,” she urged.
 

72 patients with diabetes for an average of 6.6 years

“Despite a widespread public consensus that [type 2 diabetes] is irreversible and requires drug treatment escalation, there is some evidence of the possibility of remission,” Dr. Yang and colleagues write in their article.

They aimed to evaluate the effectiveness of intermittent fasting for diabetes remission and the durability of diabetes remission at 1 year.

Diabetes remission was defined having a stable A1c less than 6.5% for at least 3 months after discontinuing all antidiabetic medications, confirmed in at least annual A1c measurements (according to a 2021 consensus statement initiated by the American Diabetes Association).

Between 2019 and 2020, the researchers enrolled 72 participants aged 38-72 years who had had type 2 diabetes (duration 1 to 11 years) and a body mass index (BMI) of 19.1-30.4 kg/m². Patients were randomized 1:1 to the intermittent fasting group or control group.

Baseline characteristics were similar in both groups. Patients were a mean age of 53 years and roughly 60% were men. They had a mean BMI of 24 kg/m², a mean duration of diabetes of 6.6 years, and a mean A1c of 7.6%, and they were taking an average of 1.8 glucose-lowering medications.  

On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.

On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50%-65% of total energy intake from carbohydrates, 15%-20% from protein, and 20%-30% from fat, and had greater than or equal to 5 g fiber per serving.

Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.

The study received funding from the National Natural Science Foundation of China. The authors have reported no relevant financial disclosures.

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

A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.

The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.

“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”

Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.

“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.

The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.

Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).

“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”

DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”

The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”

He added: “It’s a pretty historic development because we haven’t had that before.”

AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
 

A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.

The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.

“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”

Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.

“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.

The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.

Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).

“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”

DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”

The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”

He added: “It’s a pretty historic development because we haven’t had that before.”

AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
 

A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.

The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.

“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”

Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.

“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.

The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.

Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).

“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”

DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”

The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”

He added: “It’s a pretty historic development because we haven’t had that before.”

AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
 

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

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

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

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

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

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

Eating a low-carbohydrate, high-fat (LCHF) diet, instead of a high-carbohydrate, low-fat diet (HCLF), leads to significant improvements in type 2 diabetes (T2D), a new study finds.

This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.

Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.

The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.

The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.

“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
 

Study methods and results

In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.

While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.

The above changes were not sustained 3 months after finishing the diet.

“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.

Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.

“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
 

The magic of unrestricted calories

Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.

“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.

Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”

While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.

“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.

He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
 

Not the first study of its kind

In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”

Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”

He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.

“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”

He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.

Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”

The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.

Eating a low-carbohydrate, high-fat (LCHF) diet, instead of a high-carbohydrate, low-fat diet (HCLF), leads to significant improvements in type 2 diabetes (T2D), a new study finds.

This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.

Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.

The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.

The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.

“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
 

Study methods and results

In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.

While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.

The above changes were not sustained 3 months after finishing the diet.

“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.

Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.

“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
 

The magic of unrestricted calories

Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.

“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.

Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”

While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.

“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.

He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
 

Not the first study of its kind

In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”

Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”

He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.

“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”

He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.

Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”

The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.

Eating a low-carbohydrate, high-fat (LCHF) diet, instead of a high-carbohydrate, low-fat diet (HCLF), leads to significant improvements in type 2 diabetes (T2D), a new study finds.

This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.

Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.

The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.

The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.

“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
 

Study methods and results

In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.

While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.

The above changes were not sustained 3 months after finishing the diet.

“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.

Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.

“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
 

The magic of unrestricted calories

Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.

“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.

Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”

While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.

“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.

He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
 

Not the first study of its kind

In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”

Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”

He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.

“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”

He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.

Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”

The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.

CHICAGO – A smartphone app that delivers nutritional cognitive behavioral therapy (CBT) to people with type 2 diabetes produced an average 0.29 percentage point drop in hemoglobin A1c during 180 days of use compared with controls, and an average 0.37 percentage point reduction in A1c compared with baseline values in a randomized, pivotal trial with 669 adults.

Use of the app for 180 days also significantly linked with a reduced need for additional medications, reduced weight and blood pressure, and improved patient-reported outcomes, and it led to fewer adverse effects than seen in control subjects, Marc P. Bonaca, MD, reported at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The findings also showed a clear dose-response relationship: The more CBT lessons a person completed with the app, the greater the A1c reduction.

The results suggest that the app, called BT-001, “potentially provides a scalable treatment option for patients with type 2 diabetes,” concluded Dr. Bonaca.

On the basis of the results from this trial, also called BT-001, the company developing the app, Better Therapeutics, announced in September 2022 that it had filed a classification request with the Food and Drug Administration that would allow marketing authorization for the BT-001 app. Better Therapeutics envisions that once authorized by the FDA, the app would be available to people with type 2 diabetes by prescriptions written by health care providers and that the cost for the app would be covered by health insurance, explained a company spokesperson.
 

A ‘modest positive impact’

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” said Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression, “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira said in an interview.

Based on published results, the BT-001 app “seems to have a modest positive impact on glycemic control, especially among people who completed more than 10 [lesson] modules.” The evidence appears to suggest that the app “might be a good supplement to working with a behavioral health counselor.”

The BT-001 trial enrolled 669 adults with type 2 diabetes for an average of 11 years and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antidiabetes medications, including 90% on metformin and 42% on a sulfonylurea. The researchers also highlighted that the enrolled cohort of people with type 2 diabetes had a demographic profile that was “generally representative” of U.S. adults with type 2 diabetes.

The researchers told the 326 people who were randomized to the active intervention group to use the app but subjects were free to determine their frequency of use. The app introduced a new lesson module weekly that took 10-20 minutes to complete, and each weekly lesson came with associated exercises aimed at practicing skills related to behavioral beliefs.

The study’s primary efficacy endpoint was the average change from baseline in A1c compared with the 343 control participants after 90 days of app use, and 610 of the 669 enrolled participants (91%) had paired baseline and 90-day measurements. At 90 days, people in the app group had an average 0.28 percentage point decrease in their A1c compared with an average 0.11 percentage point increase among the controls, a between-group difference of 0.39 percentage points. Both the reduction from baseline with app use and the reduction relative to the controls were significant. These results appeared in an article published online in in Diabetes Care.

At the scientific sessions, Dr. Bonaca presented additional outcome data after 180 days of app use. He reported an average 0.37 percentage point reduction from baseline in A1c among app users and a 0.08 percentage point decrease from baseline among the controls, for a net 0.29 percentage point incremental decline with the app, a significant difference. At 180 days, 50% of the people in the app group had an A1c decline from baseline of at least 0.4 percentage points compared with 34% of the controls, a significant difference.


 

A dose-response relationship

Notably, app use showed a clear dose-response pattern. During 180 days of app availability, people who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use) average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times, also one-third of the intervention group, the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

Dr. Bonaca, a cardiologist and vascular medicine specialist and executive director of CPC Clinical Research and CPC Community Health, an academic research organization created by and affiliated with the University of Colorado Anschutz Medical Campus in Aurora, Colo., reported several other 180-day outcomes in the BT-001 trial:

• A 33% relative decrease in the percentage of subjects who needed during the study an additional antidiabetes medication or increased dosages of their baseline medications, which occurred at a rate of 21% among the controls and 14% among those who used the app.
• An average weight loss from baseline of 5.5 pounds using the app compared with an average 1.9 pound decrease among controls, a significant difference.
• A decline in average systolic blood pressure of 4.7 mm Hg with app use compared with a 1.8 mm Hg average decline among the controls, a significant difference.
• Significant incremental average improvements in a self-reported Short Form-12 physical component score with the app compared with controls, and increased average improvement in the PHQ9 self-reported measure of depression in app users compared with controls.
• Significantly fewer treatment-emergent adverse effects, and significantly fewer serious treatment-emergent adverse effects among the app users compared with the controls.

‘Ready for clinical use’

Based on these findings, “in my view the app is ready for [routine] clinical use,” declared Judith Hsia, MD, a cardiologist and professor of medicine at the University of Colorado in Aurora, and with Dr. Bonaca a co-lead investigator for the study.

The BT-001 app can serve as “an addition to the toolkit of diabetes treatments,” Dr. Hsia said in an interview. One key advantage of the app is that, once approved, it could be available to many more people with type 2 diabetes than would be able to receive CBT directly from a therapist. Another potential plus for the CBT app is that “the effects should be durable in contrast to medications,” which must be taken on an ongoing basis to maintain effectiveness. In addition, the safety profile “is favorable compared with drug therapies, which should appeal to health care providers,” said Dr. Hsia, chief science officer for CPC Clinical Research.

However, Dr. Shapira cited the issue that therapeutic apps “raise privacy and licensing liability concerns.”

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira had no disclosures. Dr. Hsia is a stockholder of AstraZeneca.

CHICAGO – A smartphone app that delivers nutritional cognitive behavioral therapy (CBT) to people with type 2 diabetes produced an average 0.29 percentage point drop in hemoglobin A1c during 180 days of use compared with controls, and an average 0.37 percentage point reduction in A1c compared with baseline values in a randomized, pivotal trial with 669 adults.

Use of the app for 180 days also significantly linked with a reduced need for additional medications, reduced weight and blood pressure, and improved patient-reported outcomes, and it led to fewer adverse effects than seen in control subjects, Marc P. Bonaca, MD, reported at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The findings also showed a clear dose-response relationship: The more CBT lessons a person completed with the app, the greater the A1c reduction.

The results suggest that the app, called BT-001, “potentially provides a scalable treatment option for patients with type 2 diabetes,” concluded Dr. Bonaca.

On the basis of the results from this trial, also called BT-001, the company developing the app, Better Therapeutics, announced in September 2022 that it had filed a classification request with the Food and Drug Administration that would allow marketing authorization for the BT-001 app. Better Therapeutics envisions that once authorized by the FDA, the app would be available to people with type 2 diabetes by prescriptions written by health care providers and that the cost for the app would be covered by health insurance, explained a company spokesperson.
 

A ‘modest positive impact’

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” said Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression, “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira said in an interview.

Based on published results, the BT-001 app “seems to have a modest positive impact on glycemic control, especially among people who completed more than 10 [lesson] modules.” The evidence appears to suggest that the app “might be a good supplement to working with a behavioral health counselor.”

The BT-001 trial enrolled 669 adults with type 2 diabetes for an average of 11 years and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antidiabetes medications, including 90% on metformin and 42% on a sulfonylurea. The researchers also highlighted that the enrolled cohort of people with type 2 diabetes had a demographic profile that was “generally representative” of U.S. adults with type 2 diabetes.

The researchers told the 326 people who were randomized to the active intervention group to use the app but subjects were free to determine their frequency of use. The app introduced a new lesson module weekly that took 10-20 minutes to complete, and each weekly lesson came with associated exercises aimed at practicing skills related to behavioral beliefs.

The study’s primary efficacy endpoint was the average change from baseline in A1c compared with the 343 control participants after 90 days of app use, and 610 of the 669 enrolled participants (91%) had paired baseline and 90-day measurements. At 90 days, people in the app group had an average 0.28 percentage point decrease in their A1c compared with an average 0.11 percentage point increase among the controls, a between-group difference of 0.39 percentage points. Both the reduction from baseline with app use and the reduction relative to the controls were significant. These results appeared in an article published online in in Diabetes Care.

At the scientific sessions, Dr. Bonaca presented additional outcome data after 180 days of app use. He reported an average 0.37 percentage point reduction from baseline in A1c among app users and a 0.08 percentage point decrease from baseline among the controls, for a net 0.29 percentage point incremental decline with the app, a significant difference. At 180 days, 50% of the people in the app group had an A1c decline from baseline of at least 0.4 percentage points compared with 34% of the controls, a significant difference.


 

A dose-response relationship

Notably, app use showed a clear dose-response pattern. During 180 days of app availability, people who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use) average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times, also one-third of the intervention group, the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

Dr. Bonaca, a cardiologist and vascular medicine specialist and executive director of CPC Clinical Research and CPC Community Health, an academic research organization created by and affiliated with the University of Colorado Anschutz Medical Campus in Aurora, Colo., reported several other 180-day outcomes in the BT-001 trial:

• A 33% relative decrease in the percentage of subjects who needed during the study an additional antidiabetes medication or increased dosages of their baseline medications, which occurred at a rate of 21% among the controls and 14% among those who used the app.
• An average weight loss from baseline of 5.5 pounds using the app compared with an average 1.9 pound decrease among controls, a significant difference.
• A decline in average systolic blood pressure of 4.7 mm Hg with app use compared with a 1.8 mm Hg average decline among the controls, a significant difference.
• Significant incremental average improvements in a self-reported Short Form-12 physical component score with the app compared with controls, and increased average improvement in the PHQ9 self-reported measure of depression in app users compared with controls.
• Significantly fewer treatment-emergent adverse effects, and significantly fewer serious treatment-emergent adverse effects among the app users compared with the controls.

‘Ready for clinical use’

Based on these findings, “in my view the app is ready for [routine] clinical use,” declared Judith Hsia, MD, a cardiologist and professor of medicine at the University of Colorado in Aurora, and with Dr. Bonaca a co-lead investigator for the study.

The BT-001 app can serve as “an addition to the toolkit of diabetes treatments,” Dr. Hsia said in an interview. One key advantage of the app is that, once approved, it could be available to many more people with type 2 diabetes than would be able to receive CBT directly from a therapist. Another potential plus for the CBT app is that “the effects should be durable in contrast to medications,” which must be taken on an ongoing basis to maintain effectiveness. In addition, the safety profile “is favorable compared with drug therapies, which should appeal to health care providers,” said Dr. Hsia, chief science officer for CPC Clinical Research.

However, Dr. Shapira cited the issue that therapeutic apps “raise privacy and licensing liability concerns.”

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira had no disclosures. Dr. Hsia is a stockholder of AstraZeneca.

CHICAGO – A smartphone app that delivers nutritional cognitive behavioral therapy (CBT) to people with type 2 diabetes produced an average 0.29 percentage point drop in hemoglobin A1c during 180 days of use compared with controls, and an average 0.37 percentage point reduction in A1c compared with baseline values in a randomized, pivotal trial with 669 adults.

Use of the app for 180 days also significantly linked with a reduced need for additional medications, reduced weight and blood pressure, and improved patient-reported outcomes, and it led to fewer adverse effects than seen in control subjects, Marc P. Bonaca, MD, reported at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The findings also showed a clear dose-response relationship: The more CBT lessons a person completed with the app, the greater the A1c reduction.

The results suggest that the app, called BT-001, “potentially provides a scalable treatment option for patients with type 2 diabetes,” concluded Dr. Bonaca.

On the basis of the results from this trial, also called BT-001, the company developing the app, Better Therapeutics, announced in September 2022 that it had filed a classification request with the Food and Drug Administration that would allow marketing authorization for the BT-001 app. Better Therapeutics envisions that once authorized by the FDA, the app would be available to people with type 2 diabetes by prescriptions written by health care providers and that the cost for the app would be covered by health insurance, explained a company spokesperson.
 

A ‘modest positive impact’

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” said Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression, “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira said in an interview.

Based on published results, the BT-001 app “seems to have a modest positive impact on glycemic control, especially among people who completed more than 10 [lesson] modules.” The evidence appears to suggest that the app “might be a good supplement to working with a behavioral health counselor.”

The BT-001 trial enrolled 669 adults with type 2 diabetes for an average of 11 years and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antidiabetes medications, including 90% on metformin and 42% on a sulfonylurea. The researchers also highlighted that the enrolled cohort of people with type 2 diabetes had a demographic profile that was “generally representative” of U.S. adults with type 2 diabetes.

The researchers told the 326 people who were randomized to the active intervention group to use the app but subjects were free to determine their frequency of use. The app introduced a new lesson module weekly that took 10-20 minutes to complete, and each weekly lesson came with associated exercises aimed at practicing skills related to behavioral beliefs.

The study’s primary efficacy endpoint was the average change from baseline in A1c compared with the 343 control participants after 90 days of app use, and 610 of the 669 enrolled participants (91%) had paired baseline and 90-day measurements. At 90 days, people in the app group had an average 0.28 percentage point decrease in their A1c compared with an average 0.11 percentage point increase among the controls, a between-group difference of 0.39 percentage points. Both the reduction from baseline with app use and the reduction relative to the controls were significant. These results appeared in an article published online in in Diabetes Care.

At the scientific sessions, Dr. Bonaca presented additional outcome data after 180 days of app use. He reported an average 0.37 percentage point reduction from baseline in A1c among app users and a 0.08 percentage point decrease from baseline among the controls, for a net 0.29 percentage point incremental decline with the app, a significant difference. At 180 days, 50% of the people in the app group had an A1c decline from baseline of at least 0.4 percentage points compared with 34% of the controls, a significant difference.


 

A dose-response relationship

Notably, app use showed a clear dose-response pattern. During 180 days of app availability, people who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use) average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times, also one-third of the intervention group, the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

Dr. Bonaca, a cardiologist and vascular medicine specialist and executive director of CPC Clinical Research and CPC Community Health, an academic research organization created by and affiliated with the University of Colorado Anschutz Medical Campus in Aurora, Colo., reported several other 180-day outcomes in the BT-001 trial:

• A 33% relative decrease in the percentage of subjects who needed during the study an additional antidiabetes medication or increased dosages of their baseline medications, which occurred at a rate of 21% among the controls and 14% among those who used the app.
• An average weight loss from baseline of 5.5 pounds using the app compared with an average 1.9 pound decrease among controls, a significant difference.
• A decline in average systolic blood pressure of 4.7 mm Hg with app use compared with a 1.8 mm Hg average decline among the controls, a significant difference.
• Significant incremental average improvements in a self-reported Short Form-12 physical component score with the app compared with controls, and increased average improvement in the PHQ9 self-reported measure of depression in app users compared with controls.
• Significantly fewer treatment-emergent adverse effects, and significantly fewer serious treatment-emergent adverse effects among the app users compared with the controls.

‘Ready for clinical use’

Based on these findings, “in my view the app is ready for [routine] clinical use,” declared Judith Hsia, MD, a cardiologist and professor of medicine at the University of Colorado in Aurora, and with Dr. Bonaca a co-lead investigator for the study.

The BT-001 app can serve as “an addition to the toolkit of diabetes treatments,” Dr. Hsia said in an interview. One key advantage of the app is that, once approved, it could be available to many more people with type 2 diabetes than would be able to receive CBT directly from a therapist. Another potential plus for the CBT app is that “the effects should be durable in contrast to medications,” which must be taken on an ongoing basis to maintain effectiveness. In addition, the safety profile “is favorable compared with drug therapies, which should appeal to health care providers,” said Dr. Hsia, chief science officer for CPC Clinical Research.

However, Dr. Shapira cited the issue that therapeutic apps “raise privacy and licensing liability concerns.”

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira had no disclosures. Dr. Hsia is a stockholder of AstraZeneca.

Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.

“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”

Mitchel L. Zoler/MDedge News

These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.

TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
 

Do BMI and renal function affect treatment response?

TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m² have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?

Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m² have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.

The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.

Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.

Among those with a BMI of more than 30 kg/m², patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m²) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.

These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.
 

Patients identified the agent they liked best

Dr. Hattersley and associates used the TriMaster study to also address the secondary question of which of the three tested agents patients preferred, focusing on the 457 patients who provided information on their treatment preference.

The results showed that patient preference varied: Twenty-four percent liked pioglitazone best, 33% preferred sitagliptin, and 37% said canagliflozin was their favorite, with 6% having no preference. These numbers barely budged when participants learned how well each agent worked for them in terms of reducing their A1c and lowering their BMI.

The findings also showed good correlation between patient preferences and their A1c and adverse-effect responses. The agents that patients identified as their favorites were also the drugs that lowered their A1c the most 53% of the time before they got any feedback on which one gave them their best glycemic control. Once they had this feedback, 70% preferred the most effective agent, with the results likely reflecting that patients feel better when they have improved glucose levels as well as the education patients received that lower A1c levels are better.

Patients also tended to understandably favor the agents that caused the fewest and mildest adverse effects: Sixty-eight percent of the patients who identified a favorite drug picked the one that gave them the best adverse-effect profile.

In an interview at the EASD 2022 annual meeting, Dr. Hattersley promoted the study’s design as a best-practice approach to deciding which drug to next give a person with type 2 diabetes who needs additional glycemic control.

“Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects,” he said. “Patients had overwhelming positivity about being able to choose their drug. Do it when you’re not certain which drug to prescribe,” suggested Dr. Hattersley, a professor and diabetologist at the University of Exeter, England. “We can’t know which drug a patient might prefer.”

But he stressed cautioning patients to return for treatment adjustment sooner than 4 months if they can’t tolerate a new drug they’re trying.

TriMaster received no commercial funding. Dr. Hattersley has reported no relevant financial relationships.

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

Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.

“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”

Mitchel L. Zoler/MDedge News

These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.

TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
 

Do BMI and renal function affect treatment response?

TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m² have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?

Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m² have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.

The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.

Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.

Among those with a BMI of more than 30 kg/m², patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m²) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.

These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.
 

Patients identified the agent they liked best

Dr. Hattersley and associates used the TriMaster study to also address the secondary question of which of the three tested agents patients preferred, focusing on the 457 patients who provided information on their treatment preference.

The results showed that patient preference varied: Twenty-four percent liked pioglitazone best, 33% preferred sitagliptin, and 37% said canagliflozin was their favorite, with 6% having no preference. These numbers barely budged when participants learned how well each agent worked for them in terms of reducing their A1c and lowering their BMI.

The findings also showed good correlation between patient preferences and their A1c and adverse-effect responses. The agents that patients identified as their favorites were also the drugs that lowered their A1c the most 53% of the time before they got any feedback on which one gave them their best glycemic control. Once they had this feedback, 70% preferred the most effective agent, with the results likely reflecting that patients feel better when they have improved glucose levels as well as the education patients received that lower A1c levels are better.

Patients also tended to understandably favor the agents that caused the fewest and mildest adverse effects: Sixty-eight percent of the patients who identified a favorite drug picked the one that gave them the best adverse-effect profile.

In an interview at the EASD 2022 annual meeting, Dr. Hattersley promoted the study’s design as a best-practice approach to deciding which drug to next give a person with type 2 diabetes who needs additional glycemic control.

“Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects,” he said. “Patients had overwhelming positivity about being able to choose their drug. Do it when you’re not certain which drug to prescribe,” suggested Dr. Hattersley, a professor and diabetologist at the University of Exeter, England. “We can’t know which drug a patient might prefer.”

But he stressed cautioning patients to return for treatment adjustment sooner than 4 months if they can’t tolerate a new drug they’re trying.

TriMaster received no commercial funding. Dr. Hattersley has reported no relevant financial relationships.

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

Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.

“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”

Mitchel L. Zoler/MDedge News

These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.

TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
 

Do BMI and renal function affect treatment response?

TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m² have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?

Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m² have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.

The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.

Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.

Among those with a BMI of more than 30 kg/m², patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m²) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.

These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.
 

Patients identified the agent they liked best

Dr. Hattersley and associates used the TriMaster study to also address the secondary question of which of the three tested agents patients preferred, focusing on the 457 patients who provided information on their treatment preference.

The results showed that patient preference varied: Twenty-four percent liked pioglitazone best, 33% preferred sitagliptin, and 37% said canagliflozin was their favorite, with 6% having no preference. These numbers barely budged when participants learned how well each agent worked for them in terms of reducing their A1c and lowering their BMI.

The findings also showed good correlation between patient preferences and their A1c and adverse-effect responses. The agents that patients identified as their favorites were also the drugs that lowered their A1c the most 53% of the time before they got any feedback on which one gave them their best glycemic control. Once they had this feedback, 70% preferred the most effective agent, with the results likely reflecting that patients feel better when they have improved glucose levels as well as the education patients received that lower A1c levels are better.

Patients also tended to understandably favor the agents that caused the fewest and mildest adverse effects: Sixty-eight percent of the patients who identified a favorite drug picked the one that gave them the best adverse-effect profile.

In an interview at the EASD 2022 annual meeting, Dr. Hattersley promoted the study’s design as a best-practice approach to deciding which drug to next give a person with type 2 diabetes who needs additional glycemic control.

“Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects,” he said. “Patients had overwhelming positivity about being able to choose their drug. Do it when you’re not certain which drug to prescribe,” suggested Dr. Hattersley, a professor and diabetologist at the University of Exeter, England. “We can’t know which drug a patient might prefer.”

But he stressed cautioning patients to return for treatment adjustment sooner than 4 months if they can’t tolerate a new drug they’re trying.

TriMaster received no commercial funding. Dr. Hattersley has reported no relevant financial relationships.

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