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Oral PCSK9 inhibitor shows encouraging LDL lowering
A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.
The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.
“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.
He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.
“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”
He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.
Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”
The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.
They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.
Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).
The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.
The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.
Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy.
“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.
Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
‘Super exciting’
Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.
“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”
She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”
Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”
She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”
She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).
She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”
The results were published online in the Journal of the American College of Cardiology at the time of presentation.
This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.
The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.
“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.
He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.
“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”
He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.
Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”
The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.
They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.
Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).
The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.
The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.
Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy.
“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.
Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
‘Super exciting’
Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.
“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”
She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”
Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”
She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”
She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).
She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”
The results were published online in the Journal of the American College of Cardiology at the time of presentation.
This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.
The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.
“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.
He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.
“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”
He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.
Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”
The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.
They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.
Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).
The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.
The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.
Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy.
“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.
Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
‘Super exciting’
Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.
“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”
She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”
Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”
She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”
She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).
She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”
The results were published online in the Journal of the American College of Cardiology at the time of presentation.
This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
Some, not all, ultraprocessed foods linked to type 2 diabetes
High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.
The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.
Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.
However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.
Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
Ultraprocessed food intake higher in the U.S. than in Europe
The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.
They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.
In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.
In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.
Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.
Servings per day were then used to determine individual UPF intake.
Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.
The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.
Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.
Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.
The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.
In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.
Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.
They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
Ideal is to have access to minimally processed foods
The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”
A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.
Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.
Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”
The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.
A version of this article first appeared on Medscape.com.
High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.
The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.
Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.
However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.
Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
Ultraprocessed food intake higher in the U.S. than in Europe
The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.
They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.
In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.
In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.
Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.
Servings per day were then used to determine individual UPF intake.
Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.
The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.
Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.
Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.
The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.
In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.
Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.
They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
Ideal is to have access to minimally processed foods
The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”
A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.
Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.
Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”
The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.
A version of this article first appeared on Medscape.com.
High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.
The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.
Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.
However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.
Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
Ultraprocessed food intake higher in the U.S. than in Europe
The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.
They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.
In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.
In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.
Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.
Servings per day were then used to determine individual UPF intake.
Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.
The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.
Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.
Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.
The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.
In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.
Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.
They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
Ideal is to have access to minimally processed foods
The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”
A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.
Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.
Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”
The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
Spironolactone: an ‘inexpensive, effective’ option for acne in women
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
AT THE MEDSCAPELIVE! HAWAII DERMATOLOGY SEMINAR
SCD meds: Why such ‘slow uptake’?
“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.
The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).
Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.
In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”
As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.
Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).
“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.
Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.
Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”
Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.
The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).
Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.
In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”
As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.
Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).
“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.
Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.
Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”
Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.
The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).
Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.
In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”
As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.
Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).
“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.
Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.
Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”
Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
Plant-based diet linked to better outcomes in prostate cancer
The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.
“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.
The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.
For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).
A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”
The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.
“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.
NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.
“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.
The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”
“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.
Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.
Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.
The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.
Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.
The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.
“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.
The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.
For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).
A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”
The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.
“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.
NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.
“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.
The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”
“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.
Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.
Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.
The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.
Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.
The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.
“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.
The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.
For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).
A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”
The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.
“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.
NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.
“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.
The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”
“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.
Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.
Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.
The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.
Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.
FROM ASCO GU 2023
TikTok’s fave weight loss drugs: Link to thyroid cancer?
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
The human-looking robot therapist will coach your well-being now
Do android therapists dream of electric employees?
Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.
Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.
Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.
The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.
People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.
That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.
Birthing experience is all in the mindset
Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.
Birth.
Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.
The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).
Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.
Apparently, yes.
“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”
The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.
Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?
Becoming a parent is going to create a psychological shift, no matter how you slice it.
Giant inflatable colon reported in Utah
Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.
The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.
Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.
Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.
Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:
- Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
- Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”
Do android therapists dream of electric employees?
Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.
Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.
Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.
The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.
People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.
That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.
Birthing experience is all in the mindset
Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.
Birth.
Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.
The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).
Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.
Apparently, yes.
“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”
The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.
Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?
Becoming a parent is going to create a psychological shift, no matter how you slice it.
Giant inflatable colon reported in Utah
Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.
The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.
Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.
Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.
Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:
- Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
- Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”
Do android therapists dream of electric employees?
Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.
Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.
Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.
The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.
People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.
That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.
Birthing experience is all in the mindset
Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.
Birth.
Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.
The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).
Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.
Apparently, yes.
“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”
The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.
Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?
Becoming a parent is going to create a psychological shift, no matter how you slice it.
Giant inflatable colon reported in Utah
Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.
The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.
Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.
Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.
Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:
- Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
- Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”
Establishing an advanced endoscopy practice: Tips for trainees and early faculty
Establishing an advanced endoscopy practice can appear challenging and overwhelming. It is often the culmination of more than a decade of education and training for advanced endoscopists and is usually their first foray into employment. all while creating a rewarding opportunity to provide a population with necessary services, which, more than likely, were not previously being offered at your institution or in your region.
Tip 1: Understand the current landscape
When joining a hospital-employed or private practice, it is important for the advanced endoscopist to gauge the current landscape of the job, beginning with gaining an understanding of the current services provided by your gastroenterology colleagues. This includes knowing the types of advanced endoscopy services previously provided, especially if you have partners or colleagues who perform these procedures, and their prior referral patterns, either within or outside their respective group. Also, it is important to understand the services that are provided locally at other institutions. This will allow you to develop a niche of the types of services you can provide that are not available in the current practice set-up.
Tip 2: Connect with peers, interspecialty collaborators, and referring physicians
It is important that you connect with your GI colleagues once you start a new job. This can differ in ease depending on the size of your group. For example, in a small group, it may be easier to familiarize yourself with your colleagues through regular interactions. If you are a part of a larger practice, however, it is necessary to be more proactive and set up introductory meetings/sessions. These interactions provide a great opportunity to share your goals and start building a relationship.
Efforts also should be made to reach out to primary care, hematology/oncology, surgical/radiation oncology, general surgery, and interventional radiology physicians, as these are the specialists with whom an advanced endoscopist typically has the most interaction. The relationship with these colleagues is bidirectional, as the majority of our patients need multidisciplinary decision-making and care. For example, the first time you speak to the colorectal surgeon at your institution should not be in the middle of a complication. The purpose of these introductions should not be solely to inform them of the services you are offering but to start developing a relationship in a true sense, because eventually those relationships will transform into excellent patient care.
Tip 3: Communication
Communication is a key principle in building a practice. Referring physicians often entrust you with managing a part of their patient’s medical problems. Patient/procedure outcomes should be relayed promptly to referring physicians, as this not only helps build the trust of the referring physician, but also enhances the patient’s trust in the health system, knowing that all physicians are communicating with the common goal of improving the patient’s disease course.
Communication with the referring physician is important not only after a procedure but also before it. Know that a consult is an “ask for help.” For example, even if you are not the correct specialist for a referral (for example, an inflammatory bowel disease patient was sent to an advanced endoscopist), it is good practice to take ownership of the patient and forward that person to the appropriate colleague.
Tip 4: Build a local reputation
Building upon this, it is also important to connect with other GI groups in the community, regardless of whether they have their own affiliated advanced endoscopists. This helps determine the advanced endoscopy services being offered regionally, which will further allow an understanding of the unmet needs of the region. In addition, building a relationship with local advanced endoscopists in the region can help establish a collaborative relationship going forward, rather than a contentious/competitive dynamic.
Tip 5: Advance your skills
As advanced endoscopy fellows are aware, completing an advanced endoscopy fellowship allows for building a strong foundation of skills, which will continue to refine and grow as you advance in your career.
Depending on your skill-set and training, the first year should focus on developing and establishing “your style” (since the training is tailored to follow the practice patterns of your mentors). The first few months are good to focus on refining endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, endoscopic mucosal resection, and luminal stenting techniques. As you start to build a reputation of being “safe, thoughtful, and skilled” and depending on your interests and goals, continued engagement in the advanced endoscopy community to understand new technologies/procedures is helpful. It is important to remember that new skills and procedures can be introduced in your practice, but this should be done in a timely and patient manner. You should appropriately educate and train yourself for such procedures through educational conferences/courses, shadowing and routine engagement with mentors, and collaboration with industry partners.
Tip 6: Team building
From a procedural standpoint, certain staff members should be recognized to be part of or lead an “advanced endoscopy team,” with a goal of dedicated exposure to a high volume of complex procedures. This builds camaraderie and trust within the team of advanced endoscopy nurses and technicians going forward, which is crucial to introducing and building a high-complexity procedural service. This is also an excellent opportunity to partner with our industry colleagues to ensure that they can train your team on the use of novel devices.
Tip 7: Offering new services to your patients
Advanced endoscopy is a rapidly evolving specialty, and new procedures, technology, and devices are allowing us to provide minimally invasive options to our patients. It is important that prior to introducing new services and programs, your hospital/practice administration should be informed about any such plans. Also, all potential collaborating services (surgery, interventional radiology, etc.) should be part of the decision-making to ensure patients receive the best possible multidisciplinary care.
Tip 8: Mentorship and peer-mentorship
Establishing a network of regional and national advanced endoscopy colleagues and mentors is critical. This may be harder to develop in community-based and private practice, where one may feel that they are on an “island.” Engagement with national organizations, use of social media, and other avenues are excellent ways to build this network. Advanced endoscopic procedures also are associated with higher rates of adverse events, so having a peer-support group to provide emotional and moral support when these adverse events occur also is important. Such a network also includes those collaborating specialties to which you would refer (surgical oncology, thoracic surgery, etc.). Being involved in local tumor boards and “gut clubs” is another way of remaining engaged and not feeling isolated.
Tip 9: Have fun
Advanced endoscopy can be busy, as well as physically and mentally exhausting. It is important to maintain a good work-life balance. In addition, planning scheduled retreats or social events with your advanced endoscopy team (nurses, technicians, schedulers, colleagues) is important not only to show appreciation, but also to help build camaraderie and develop relationships.
Tip 10: Remember your ‘why’
Often times, there can be stressors associated with building a practice and increasing your volume, therefore, it is always important to remember why you became a medical professional and advanced endoscopist. This will get you through the days where you had a complication or when things didn’t go as planned.
Conclusion
Lastly, it is important to keep revisiting your skill sets and practice and evaluate what is working well and what can be improved. To all the advanced endoscopists starting their careers: Be patient and have a positive attitude! The leaders in our field did not become so overnight, and an advanced endoscopy–based career resembles a marathon rather than a sprint. Mistakes during procedures and practice building can be made, but how you grow and learn from those mistakes is what determines how likely you are to succeed going forward. Respect and acknowledge your staff, your collaborating physicians, and mentors. It takes time and effort to develop an advanced endoscopy practice. Being proud of your achievements and promoting procedural and patient care advances that you have made are beneficial and encouraged. We are fortunate to be in an ever-evolving specialty, and it is an exciting time to be practicing advanced endoscopy. Good luck!
Dr. Soudagar is a gastroenterologist at Northwestern Medical Group, Lake Forest, Ill. Dr. Bilal, assistant professor of medicine at the University of Minnesota, Minneapolis, is an advanced endoscopist and gastroenterologist at Minneapolis VA Medical Center. The authors have no conflicts of interest.
Establishing an advanced endoscopy practice can appear challenging and overwhelming. It is often the culmination of more than a decade of education and training for advanced endoscopists and is usually their first foray into employment. all while creating a rewarding opportunity to provide a population with necessary services, which, more than likely, were not previously being offered at your institution or in your region.
Tip 1: Understand the current landscape
When joining a hospital-employed or private practice, it is important for the advanced endoscopist to gauge the current landscape of the job, beginning with gaining an understanding of the current services provided by your gastroenterology colleagues. This includes knowing the types of advanced endoscopy services previously provided, especially if you have partners or colleagues who perform these procedures, and their prior referral patterns, either within or outside their respective group. Also, it is important to understand the services that are provided locally at other institutions. This will allow you to develop a niche of the types of services you can provide that are not available in the current practice set-up.
Tip 2: Connect with peers, interspecialty collaborators, and referring physicians
It is important that you connect with your GI colleagues once you start a new job. This can differ in ease depending on the size of your group. For example, in a small group, it may be easier to familiarize yourself with your colleagues through regular interactions. If you are a part of a larger practice, however, it is necessary to be more proactive and set up introductory meetings/sessions. These interactions provide a great opportunity to share your goals and start building a relationship.
Efforts also should be made to reach out to primary care, hematology/oncology, surgical/radiation oncology, general surgery, and interventional radiology physicians, as these are the specialists with whom an advanced endoscopist typically has the most interaction. The relationship with these colleagues is bidirectional, as the majority of our patients need multidisciplinary decision-making and care. For example, the first time you speak to the colorectal surgeon at your institution should not be in the middle of a complication. The purpose of these introductions should not be solely to inform them of the services you are offering but to start developing a relationship in a true sense, because eventually those relationships will transform into excellent patient care.
Tip 3: Communication
Communication is a key principle in building a practice. Referring physicians often entrust you with managing a part of their patient’s medical problems. Patient/procedure outcomes should be relayed promptly to referring physicians, as this not only helps build the trust of the referring physician, but also enhances the patient’s trust in the health system, knowing that all physicians are communicating with the common goal of improving the patient’s disease course.
Communication with the referring physician is important not only after a procedure but also before it. Know that a consult is an “ask for help.” For example, even if you are not the correct specialist for a referral (for example, an inflammatory bowel disease patient was sent to an advanced endoscopist), it is good practice to take ownership of the patient and forward that person to the appropriate colleague.
Tip 4: Build a local reputation
Building upon this, it is also important to connect with other GI groups in the community, regardless of whether they have their own affiliated advanced endoscopists. This helps determine the advanced endoscopy services being offered regionally, which will further allow an understanding of the unmet needs of the region. In addition, building a relationship with local advanced endoscopists in the region can help establish a collaborative relationship going forward, rather than a contentious/competitive dynamic.
Tip 5: Advance your skills
As advanced endoscopy fellows are aware, completing an advanced endoscopy fellowship allows for building a strong foundation of skills, which will continue to refine and grow as you advance in your career.
Depending on your skill-set and training, the first year should focus on developing and establishing “your style” (since the training is tailored to follow the practice patterns of your mentors). The first few months are good to focus on refining endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, endoscopic mucosal resection, and luminal stenting techniques. As you start to build a reputation of being “safe, thoughtful, and skilled” and depending on your interests and goals, continued engagement in the advanced endoscopy community to understand new technologies/procedures is helpful. It is important to remember that new skills and procedures can be introduced in your practice, but this should be done in a timely and patient manner. You should appropriately educate and train yourself for such procedures through educational conferences/courses, shadowing and routine engagement with mentors, and collaboration with industry partners.
Tip 6: Team building
From a procedural standpoint, certain staff members should be recognized to be part of or lead an “advanced endoscopy team,” with a goal of dedicated exposure to a high volume of complex procedures. This builds camaraderie and trust within the team of advanced endoscopy nurses and technicians going forward, which is crucial to introducing and building a high-complexity procedural service. This is also an excellent opportunity to partner with our industry colleagues to ensure that they can train your team on the use of novel devices.
Tip 7: Offering new services to your patients
Advanced endoscopy is a rapidly evolving specialty, and new procedures, technology, and devices are allowing us to provide minimally invasive options to our patients. It is important that prior to introducing new services and programs, your hospital/practice administration should be informed about any such plans. Also, all potential collaborating services (surgery, interventional radiology, etc.) should be part of the decision-making to ensure patients receive the best possible multidisciplinary care.
Tip 8: Mentorship and peer-mentorship
Establishing a network of regional and national advanced endoscopy colleagues and mentors is critical. This may be harder to develop in community-based and private practice, where one may feel that they are on an “island.” Engagement with national organizations, use of social media, and other avenues are excellent ways to build this network. Advanced endoscopic procedures also are associated with higher rates of adverse events, so having a peer-support group to provide emotional and moral support when these adverse events occur also is important. Such a network also includes those collaborating specialties to which you would refer (surgical oncology, thoracic surgery, etc.). Being involved in local tumor boards and “gut clubs” is another way of remaining engaged and not feeling isolated.
Tip 9: Have fun
Advanced endoscopy can be busy, as well as physically and mentally exhausting. It is important to maintain a good work-life balance. In addition, planning scheduled retreats or social events with your advanced endoscopy team (nurses, technicians, schedulers, colleagues) is important not only to show appreciation, but also to help build camaraderie and develop relationships.
Tip 10: Remember your ‘why’
Often times, there can be stressors associated with building a practice and increasing your volume, therefore, it is always important to remember why you became a medical professional and advanced endoscopist. This will get you through the days where you had a complication or when things didn’t go as planned.
Conclusion
Lastly, it is important to keep revisiting your skill sets and practice and evaluate what is working well and what can be improved. To all the advanced endoscopists starting their careers: Be patient and have a positive attitude! The leaders in our field did not become so overnight, and an advanced endoscopy–based career resembles a marathon rather than a sprint. Mistakes during procedures and practice building can be made, but how you grow and learn from those mistakes is what determines how likely you are to succeed going forward. Respect and acknowledge your staff, your collaborating physicians, and mentors. It takes time and effort to develop an advanced endoscopy practice. Being proud of your achievements and promoting procedural and patient care advances that you have made are beneficial and encouraged. We are fortunate to be in an ever-evolving specialty, and it is an exciting time to be practicing advanced endoscopy. Good luck!
Dr. Soudagar is a gastroenterologist at Northwestern Medical Group, Lake Forest, Ill. Dr. Bilal, assistant professor of medicine at the University of Minnesota, Minneapolis, is an advanced endoscopist and gastroenterologist at Minneapolis VA Medical Center. The authors have no conflicts of interest.
Establishing an advanced endoscopy practice can appear challenging and overwhelming. It is often the culmination of more than a decade of education and training for advanced endoscopists and is usually their first foray into employment. all while creating a rewarding opportunity to provide a population with necessary services, which, more than likely, were not previously being offered at your institution or in your region.
Tip 1: Understand the current landscape
When joining a hospital-employed or private practice, it is important for the advanced endoscopist to gauge the current landscape of the job, beginning with gaining an understanding of the current services provided by your gastroenterology colleagues. This includes knowing the types of advanced endoscopy services previously provided, especially if you have partners or colleagues who perform these procedures, and their prior referral patterns, either within or outside their respective group. Also, it is important to understand the services that are provided locally at other institutions. This will allow you to develop a niche of the types of services you can provide that are not available in the current practice set-up.
Tip 2: Connect with peers, interspecialty collaborators, and referring physicians
It is important that you connect with your GI colleagues once you start a new job. This can differ in ease depending on the size of your group. For example, in a small group, it may be easier to familiarize yourself with your colleagues through regular interactions. If you are a part of a larger practice, however, it is necessary to be more proactive and set up introductory meetings/sessions. These interactions provide a great opportunity to share your goals and start building a relationship.
Efforts also should be made to reach out to primary care, hematology/oncology, surgical/radiation oncology, general surgery, and interventional radiology physicians, as these are the specialists with whom an advanced endoscopist typically has the most interaction. The relationship with these colleagues is bidirectional, as the majority of our patients need multidisciplinary decision-making and care. For example, the first time you speak to the colorectal surgeon at your institution should not be in the middle of a complication. The purpose of these introductions should not be solely to inform them of the services you are offering but to start developing a relationship in a true sense, because eventually those relationships will transform into excellent patient care.
Tip 3: Communication
Communication is a key principle in building a practice. Referring physicians often entrust you with managing a part of their patient’s medical problems. Patient/procedure outcomes should be relayed promptly to referring physicians, as this not only helps build the trust of the referring physician, but also enhances the patient’s trust in the health system, knowing that all physicians are communicating with the common goal of improving the patient’s disease course.
Communication with the referring physician is important not only after a procedure but also before it. Know that a consult is an “ask for help.” For example, even if you are not the correct specialist for a referral (for example, an inflammatory bowel disease patient was sent to an advanced endoscopist), it is good practice to take ownership of the patient and forward that person to the appropriate colleague.
Tip 4: Build a local reputation
Building upon this, it is also important to connect with other GI groups in the community, regardless of whether they have their own affiliated advanced endoscopists. This helps determine the advanced endoscopy services being offered regionally, which will further allow an understanding of the unmet needs of the region. In addition, building a relationship with local advanced endoscopists in the region can help establish a collaborative relationship going forward, rather than a contentious/competitive dynamic.
Tip 5: Advance your skills
As advanced endoscopy fellows are aware, completing an advanced endoscopy fellowship allows for building a strong foundation of skills, which will continue to refine and grow as you advance in your career.
Depending on your skill-set and training, the first year should focus on developing and establishing “your style” (since the training is tailored to follow the practice patterns of your mentors). The first few months are good to focus on refining endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, endoscopic mucosal resection, and luminal stenting techniques. As you start to build a reputation of being “safe, thoughtful, and skilled” and depending on your interests and goals, continued engagement in the advanced endoscopy community to understand new technologies/procedures is helpful. It is important to remember that new skills and procedures can be introduced in your practice, but this should be done in a timely and patient manner. You should appropriately educate and train yourself for such procedures through educational conferences/courses, shadowing and routine engagement with mentors, and collaboration with industry partners.
Tip 6: Team building
From a procedural standpoint, certain staff members should be recognized to be part of or lead an “advanced endoscopy team,” with a goal of dedicated exposure to a high volume of complex procedures. This builds camaraderie and trust within the team of advanced endoscopy nurses and technicians going forward, which is crucial to introducing and building a high-complexity procedural service. This is also an excellent opportunity to partner with our industry colleagues to ensure that they can train your team on the use of novel devices.
Tip 7: Offering new services to your patients
Advanced endoscopy is a rapidly evolving specialty, and new procedures, technology, and devices are allowing us to provide minimally invasive options to our patients. It is important that prior to introducing new services and programs, your hospital/practice administration should be informed about any such plans. Also, all potential collaborating services (surgery, interventional radiology, etc.) should be part of the decision-making to ensure patients receive the best possible multidisciplinary care.
Tip 8: Mentorship and peer-mentorship
Establishing a network of regional and national advanced endoscopy colleagues and mentors is critical. This may be harder to develop in community-based and private practice, where one may feel that they are on an “island.” Engagement with national organizations, use of social media, and other avenues are excellent ways to build this network. Advanced endoscopic procedures also are associated with higher rates of adverse events, so having a peer-support group to provide emotional and moral support when these adverse events occur also is important. Such a network also includes those collaborating specialties to which you would refer (surgical oncology, thoracic surgery, etc.). Being involved in local tumor boards and “gut clubs” is another way of remaining engaged and not feeling isolated.
Tip 9: Have fun
Advanced endoscopy can be busy, as well as physically and mentally exhausting. It is important to maintain a good work-life balance. In addition, planning scheduled retreats or social events with your advanced endoscopy team (nurses, technicians, schedulers, colleagues) is important not only to show appreciation, but also to help build camaraderie and develop relationships.
Tip 10: Remember your ‘why’
Often times, there can be stressors associated with building a practice and increasing your volume, therefore, it is always important to remember why you became a medical professional and advanced endoscopist. This will get you through the days where you had a complication or when things didn’t go as planned.
Conclusion
Lastly, it is important to keep revisiting your skill sets and practice and evaluate what is working well and what can be improved. To all the advanced endoscopists starting their careers: Be patient and have a positive attitude! The leaders in our field did not become so overnight, and an advanced endoscopy–based career resembles a marathon rather than a sprint. Mistakes during procedures and practice building can be made, but how you grow and learn from those mistakes is what determines how likely you are to succeed going forward. Respect and acknowledge your staff, your collaborating physicians, and mentors. It takes time and effort to develop an advanced endoscopy practice. Being proud of your achievements and promoting procedural and patient care advances that you have made are beneficial and encouraged. We are fortunate to be in an ever-evolving specialty, and it is an exciting time to be practicing advanced endoscopy. Good luck!
Dr. Soudagar is a gastroenterologist at Northwestern Medical Group, Lake Forest, Ill. Dr. Bilal, assistant professor of medicine at the University of Minnesota, Minneapolis, is an advanced endoscopist and gastroenterologist at Minneapolis VA Medical Center. The authors have no conflicts of interest.