Diabetes

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors rather than metformin as first-line treatment for type 2 diabetes appears to cut the risk for heart failure hospitalization but not myocardial infarction, stroke, or all-cause mortality, a new analysis of real-world data suggests.

Safety findings were similar, except for the fact that genital infections were more common with SGLT-2 inhibitors.

The study was conducted using claims data from two large U.S. insurance databases and Medicare. Propensity score matching was used to account for baseline differences.

The study was conducted by HoJin Shin, BPharm, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues. The findings were published online in Annals of Internal Medicine.

“Those who start SGLT-2 inhibitors as first line show similar risks, compared with metformin in MI, stroke, and all-cause mortality outcomes. Strikingly and consistently, SGLT-2 inhibitors show lower risk for hospitalization for heart failure, which is consistent with the findings from cardiovascular outcomes trials,” Dr. Shin said in an interview.
 

Just a beginning step, although trial probably wasn’t long enough

However, she added, “I don’t want to overstate anything. ... We aren’t powered enough to investigate who would benefit the most. ... As a pharmacoepidemiologist, I think it’s my duty to provide high-quality evidence so we can actually help physicians and patients make better decisions on their medication. Our current research is just a beginning step.”

Asked to comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, told this news organization, “This study generally confirmed conclusions from published RCTs [randomized clinical trials]. No real surprises, albeit the conclusions may not fully support some of the most enthusiastic claims for SGLT-2 inhibitors with respect to MI, stroke, and cardiovascular death.”

Indeed, Dr. Taylor noted that only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events.

In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes.

He also pointed out that those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin.

“Viewed in this light, it’s probably not surprising that the present study did not demonstrate a robust benefit for SGLT-2 inhibitors to decrease [major adverse CV events].”

The duration of follow-up in the current study is also a limitation, he added.

“The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it’s probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events.”

Nevertheless, he said, “it provides strong support for benefit with respect to decreasing risk of hospitalization for heart failure.”

He noted that while metformin is currently significantly cheaper than any SGLT-2 inhibitors, once the latter become available as generics, they will be cheaper, and this will likely have a bearing on prescribing decisions.

“Availability of generic SGLT-2 inhibitors offers potential to transform prescribing patterns for type 2 diabetes,” he noted.

First-line SGLT2 inhibitors versus metformin: Most outcomes similar

The study data came from two commercial U.S. health insurance databases, Optum Clinfomatics Data Mart and IBM Marketscan, and from Medicare fee-for-service enrollees.

From April 2013 through March 2020, a total of 9,334 patients began treatment with first-line SGLT-2 inhibitors; 819,973 patients began taking metformin. After 1:2 propensity score matching for confounders, there were 8,613 participants in the SGLT-2 inhibitor group and 17,226 in the group that began treatment with metformin.

The mean follow-up times were 10.7 months for patients taking SGLT-2 inhibitors and 12.2 months for patients taking metformin.

Incidence rates per 1,000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 versus 16.2 for SLGT-2 inhibitors versus metformin, not a significant difference (hazard ratio, 0.96).

However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 versus 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months.

Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality.

Genital infections were significantly more common with SGLT-2 inhibitors (54.1 vs. 23.7 per 1,000 person-years; HR, 2.19). Other safety measures were similar, including acute kidney injury, bone fractures, severe hypoglycemia, diabetic ketoacidosis, and lower-limb amputations.
 

How does cost factor in?

A sensitivity analysis aimed at examining the possible effect of unmeasured socioeconomic status showed no difference in cardiovascular benefit for first-line SGLT-2 inhibitors and metformin, compared with first-line dipeptidyl peptidase–4 (DPP-4) inhibitors, which cost more than metformin; it is not known what effect DPP-4 inhibitors have on the cardiovascular outcomes of interest.

Cost and insurance coverage factor into the benefit/risk calculation. Metformin is far less costly than any of the SGLT-2 inhibitors – roughly $10 to $20 per month, compared with more than $500 a month.

However, “for some fortunate patients with the most generous pharmacy benefit insurance coverage, the out-of-pocket cost of brand name drugs like SGLT-2 inhibitors is substantially lower,” Dr. Taylor noted.

He said that the current study “raises questions about whether the clinical benefits of SGLT-2 inhibitors as initial monotherapy justify the higher price relative to metformin. The data in this paper suggest that the value case for SGLT-2 inhibitors is strongest for patients with the greatest risk to be hospitalized for heart failure.”

Indeed, Dr. Shin said, “Once we get more information, it may just help in extending the coverage from insurance companies and Medicare/Medicaid, to lower the barrier to access.”

Dr. Taylor reiterated that patents on some of the early SGLT-2 inhibitors are expected to expire in the next few years, which would make it possible for generic versions to be approved. “At that point, prices would likely fall, possibly to levels similar to metformin.”

The study was funded by grant support from the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Harvard Medical School, the National Institute on Aging, and the Patient-Centered Outcomes Research Institute. Dr. Shin has disclosed no relevant financial relationships. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

SAN DIEGO – Endoscopic sleeve gastroplasty (ESG) led to sustained weight loss and a reduction of cardiometabolic syndrome comorbidities at 5 years, according to a new retrospective analysis of prospectively collected data.

Improved cardiometabolic outcomes following bariatric surgery have been well documented, but ESG is relatively new, so its outcomes haven’t been as well described. The outcomes are encouraging, though not as good as those of bariatric surgery. “It’s still better, but only one percent of the patients undergo the surgery, even though they’re candidates,” said Donevan Westerveld, MD, who presented the study at the annual Digestive Disease Week^® (DDW).

Jim Kling/MDedge News

Improvements included weight, HbA1c percentage, hypertension, and low-density lipoprotein. “I was surprised that the LDL decreased numerically, not so much HbA1c and hypertension. I knew [those] would come down with weight loss,” said Dr. Westerveld, a second-year fellow at Weill Cornell Medicine, New York.

He also called for guidelines for ESG. “Given the fact there’s an improvement of comorbid conditions, it’s something we should look at,” said Dr. Westerveld.

“It’s fascinating because it tells us two important things about endoscopic sleeve gastroplasty. One, [the benefit] in the majority of cases lasts at least 5 years. The weight loss is durable. And then it tells us that there’s improvement in all the cardiometabolic factors that matter, and those effects are seen all the way up to 5 years. So very important findings that support the benefits of the endoscopic gastroplasty in obesity and cardiometabolic risks and metabolic syndrome,” said Andres Acosta, MD, PhD, a comoderator of the session where the study was presented. He is assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic in Rochester, Minn.

The findings should also encourage more innovation. “Doing these endoscopic procedures, having successful results that hold for 5 years, opens the path for new and better procedures, so we have better weight loss,” said Dr. Acosta.

Previous work by Dr. Westerveld’s group found benefits of ESG at 12 months, including improvements in mean HbA1c levels in all patients (6.1%-5.5%; P = .05) and those with diabetes or prediabetes (6.6%-5.6%; P = .02), reduction in mean waist circumference (119.66-92.75 cm; P < .001), reduction in systolic blood pressure (129.02-122.23 mg/dL; P = .023), triglycerides (131.84-92.36 mg/dL; P = .017), and alanine aminotransferase (ALT, 32.26-20.68 mg/dL; P < .001).

In the new study, the group followed 255 patients at 1, 3, and 5 years post procedure who were treated consecutively at Weill Cornell Medicine from 2013 to 2021. Among the patients were those who had failed weight loss measures and were either not candidates for surgery or had refused surgery.

The mean age was 45.5 years, 69% were female, and the mean body mass index was 38.6. Overall, 40.3% had prediabetes or diabetes, 26.7% had hypertension, 60.8% had low-density lipoprotein (LDL) above 100 mg/dL, and 29.3% had elevated ALT. Sixty-six percent had been followed up at 1 year, 78% at 3 years, and 87% at 5 years.

Weight loss averaged 15.7% at 1 year and 15.3% at year 5, and the values were statistically significant. Among patients with diabetes and prediabetes, HbA1c percentage dropped from a baseline value of 6.4% to 5.7% at year 1, 6.1% at year 3, and 5.8% at year 5 (P < .05 for all). For all patients, the value dropped from 5.8% at baseline to 5.6% at year 1, 5.7% at year 3, and 5.4% at year 5. These changes were not statistically significant.

Systolic blood pressure went down among patients with stage 1 hypertension, from 135 mm Hg at baseline to 122 at year 1 and 121 at year 3 (P < .05 or both), but the mean value increased to 129 at year 5 and was not statistically significant. LDL among all patients declined from 136 mg/dL at baseline to 125 at year 1 (nonsignificant), 115 at year 3 (P < .05), and 109 at year 5 (P < .05). Alanine transaminase values declined from about 29 at baseline to 25 at year 1, 26 at year 3, and 24 at year 5 (P < .05 for all).

Serious adverse events were rare, occurring in just two cases (< 1%).

The study was limited by lack of a sham control, and its retrospective data may have included bias because many of the procedures were not paid for by insurance, leading to high rates of self-pay.

Dr. Westerveld has no relevant financial disclosures. Dr. Acosta is a founder of Gila Therapeutics and Phenomix Sciences. Dr. Acosta consults for Amgen, Gila Therapeutics, Rhythm Pharmaceuticals, and General Mills. He has received funding from Rhythm, Novo Nordisk, Apollo Endosurgery, and USGI Medical.

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

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

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

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

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

Key clinical point: A diet containing red meat did not have any significant effect on most glycemic and insulinemic risk factors associated with type 2 diabetes (T2D), but it led to a significant reduction in postprandial glucose level compared with a diet containing less or no red meat.

Major finding: A diet with vs without or less meat had no significant effect on insulin sensitivity (standardized mean difference [SMD] −0.11; 95% CI −0.39 to 0.16), insulin resistance (SMD 0.11; 95% CI −0.24 to 0.45), fasting glucose level (SMD 0.13; 95% CI −0.04 to 0.29), and fasting insulin level (SMD 0.08; 95% CI −0.16 to 0.32), but it significantly reduced the postprandial glucose level (SMD −0.44; P < .001).

Study details: Findings are from a meta-analysis of 21 randomized controlled trials that evaluated the association between red meat intake and T2D risk.

Disclosures: This study was funded by the Beef Checkoff. Three authors declared being employees of Midwest Biomedical Research (USA), which received research funding from Beef Checkoff and National Pork Board.

Source: Sanders LM et al. Red meat consumption and risk factors for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2022 (May 5). Doi: 10.1038/s41430-022-01150-1

Key clinical point: A diet containing red meat did not have any significant effect on most glycemic and insulinemic risk factors associated with type 2 diabetes (T2D), but it led to a significant reduction in postprandial glucose level compared with a diet containing less or no red meat.

Major finding: A diet with vs without or less meat had no significant effect on insulin sensitivity (standardized mean difference [SMD] −0.11; 95% CI −0.39 to 0.16), insulin resistance (SMD 0.11; 95% CI −0.24 to 0.45), fasting glucose level (SMD 0.13; 95% CI −0.04 to 0.29), and fasting insulin level (SMD 0.08; 95% CI −0.16 to 0.32), but it significantly reduced the postprandial glucose level (SMD −0.44; P < .001).

Study details: Findings are from a meta-analysis of 21 randomized controlled trials that evaluated the association between red meat intake and T2D risk.

Disclosures: This study was funded by the Beef Checkoff. Three authors declared being employees of Midwest Biomedical Research (USA), which received research funding from Beef Checkoff and National Pork Board.

Source: Sanders LM et al. Red meat consumption and risk factors for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2022 (May 5). Doi: 10.1038/s41430-022-01150-1

Key clinical point: A diet containing red meat did not have any significant effect on most glycemic and insulinemic risk factors associated with type 2 diabetes (T2D), but it led to a significant reduction in postprandial glucose level compared with a diet containing less or no red meat.

Major finding: A diet with vs without or less meat had no significant effect on insulin sensitivity (standardized mean difference [SMD] −0.11; 95% CI −0.39 to 0.16), insulin resistance (SMD 0.11; 95% CI −0.24 to 0.45), fasting glucose level (SMD 0.13; 95% CI −0.04 to 0.29), and fasting insulin level (SMD 0.08; 95% CI −0.16 to 0.32), but it significantly reduced the postprandial glucose level (SMD −0.44; P < .001).

Study details: Findings are from a meta-analysis of 21 randomized controlled trials that evaluated the association between red meat intake and T2D risk.

Disclosures: This study was funded by the Beef Checkoff. Three authors declared being employees of Midwest Biomedical Research (USA), which received research funding from Beef Checkoff and National Pork Board.

Source: Sanders LM et al. Red meat consumption and risk factors for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2022 (May 5). Doi: 10.1038/s41430-022-01150-1

Key clinical point: Cotadutide vs placebo was safe and effective in reducing body weight, glycated hemoglobin (HbA1c) level, and fasting plasma glucose level in patients with type 2 diabetes mellitus (T2D) and overweight or obesity.

Major finding: Percent decrease in body weight (mean difference [MD] 3.31; 95% CI 2.76-3.38) and glucose area under the plasma concentration curve (MD 30.15; 95% CI 23.18-37.12) and reduction in HbA1c (MD 0.68; 95% CI 0.58-0.79) and fasting plasma glucose (MD 31.31 mg/dL; 95% CI 22.59-40.04) levels over time were higher with cotadutide than placebo. Treatment-emergent serious adverse events were not significantly different between the treatment groups.

Study details: Findings are from a meta-analysis of eight randomized controlled trials including 1259 patients with T2D (body mass index 22-40 kg/m²) who received cotadutide (n = 890), placebo (n = 259), or other interventions (n = 110).

Disclosures: The study was funded by the Science, Technology & Innovation Funding Authority in cooperation with The Egyptian Knowledge Bank. The authors declared no conflicts of interest.

Source: Ali MM et al. Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis BMC Endocr Disord. 2022;22:113 (Apr 29). Doi: 10.1186/s12902-022-01031-5

Key clinical point: Cotadutide vs placebo was safe and effective in reducing body weight, glycated hemoglobin (HbA1c) level, and fasting plasma glucose level in patients with type 2 diabetes mellitus (T2D) and overweight or obesity.

Major finding: Percent decrease in body weight (mean difference [MD] 3.31; 95% CI 2.76-3.38) and glucose area under the plasma concentration curve (MD 30.15; 95% CI 23.18-37.12) and reduction in HbA1c (MD 0.68; 95% CI 0.58-0.79) and fasting plasma glucose (MD 31.31 mg/dL; 95% CI 22.59-40.04) levels over time were higher with cotadutide than placebo. Treatment-emergent serious adverse events were not significantly different between the treatment groups.

Study details: Findings are from a meta-analysis of eight randomized controlled trials including 1259 patients with T2D (body mass index 22-40 kg/m²) who received cotadutide (n = 890), placebo (n = 259), or other interventions (n = 110).

Disclosures: The study was funded by the Science, Technology & Innovation Funding Authority in cooperation with The Egyptian Knowledge Bank. The authors declared no conflicts of interest.

Source: Ali MM et al. Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis BMC Endocr Disord. 2022;22:113 (Apr 29). Doi: 10.1186/s12902-022-01031-5

Key clinical point: Cotadutide vs placebo was safe and effective in reducing body weight, glycated hemoglobin (HbA1c) level, and fasting plasma glucose level in patients with type 2 diabetes mellitus (T2D) and overweight or obesity.

Major finding: Percent decrease in body weight (mean difference [MD] 3.31; 95% CI 2.76-3.38) and glucose area under the plasma concentration curve (MD 30.15; 95% CI 23.18-37.12) and reduction in HbA1c (MD 0.68; 95% CI 0.58-0.79) and fasting plasma glucose (MD 31.31 mg/dL; 95% CI 22.59-40.04) levels over time were higher with cotadutide than placebo. Treatment-emergent serious adverse events were not significantly different between the treatment groups.

Study details: Findings are from a meta-analysis of eight randomized controlled trials including 1259 patients with T2D (body mass index 22-40 kg/m²) who received cotadutide (n = 890), placebo (n = 259), or other interventions (n = 110).

Disclosures: The study was funded by the Science, Technology & Innovation Funding Authority in cooperation with The Egyptian Knowledge Bank. The authors declared no conflicts of interest.

Source: Ali MM et al. Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis BMC Endocr Disord. 2022;22:113 (Apr 29). Doi: 10.1186/s12902-022-01031-5

Key clinical point: In patients with type 2 diabetes mellitus (T2D) for ≥10 years, metformin use vs no use was significantly associated with a lower risk for any and early age-related macular degeneration (AMD) but not late AMD.

Major finding: A significant association was observed between metformin use and any AMD (adjusted odds ratio [aOR] 0.24) and early AMD (aOR 0.17; both P < .0001), but not late AMD (P = .0619). Prolonged use (>5 years) and high cumulative dose (>3500 g) of metformin reduced AMD risk (P_trend = .0007).

Study details: This retrospective study included 324 patients aged ≥50 years diagnosed with T2D for ≥10 years, of which 209 were metformin users and 115 were metformin nonusers.

Disclosures: This study was funded by Hospital Youth Research Fund of China-Japan

Friendship Hospital and Beijing University of Chemical Technology-China-Japan Friendship Hospital Biomedical Translational Engineering Research Center Joint Fund. The authors declared no competing interests.

Source: Jiang J et al. Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: A retrospective study. BMJ Open. 2022;12:e054420 (Apr 26). Doi: 10.1136/bmjopen-2021-054420

Key clinical point: In patients with type 2 diabetes mellitus (T2D) for ≥10 years, metformin use vs no use was significantly associated with a lower risk for any and early age-related macular degeneration (AMD) but not late AMD.

Major finding: A significant association was observed between metformin use and any AMD (adjusted odds ratio [aOR] 0.24) and early AMD (aOR 0.17; both P < .0001), but not late AMD (P = .0619). Prolonged use (>5 years) and high cumulative dose (>3500 g) of metformin reduced AMD risk (P_trend = .0007).

Study details: This retrospective study included 324 patients aged ≥50 years diagnosed with T2D for ≥10 years, of which 209 were metformin users and 115 were metformin nonusers.

Disclosures: This study was funded by Hospital Youth Research Fund of China-Japan

Friendship Hospital and Beijing University of Chemical Technology-China-Japan Friendship Hospital Biomedical Translational Engineering Research Center Joint Fund. The authors declared no competing interests.

Source: Jiang J et al. Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: A retrospective study. BMJ Open. 2022;12:e054420 (Apr 26). Doi: 10.1136/bmjopen-2021-054420

Key clinical point: In patients with type 2 diabetes mellitus (T2D) for ≥10 years, metformin use vs no use was significantly associated with a lower risk for any and early age-related macular degeneration (AMD) but not late AMD.

Major finding: A significant association was observed between metformin use and any AMD (adjusted odds ratio [aOR] 0.24) and early AMD (aOR 0.17; both P < .0001), but not late AMD (P = .0619). Prolonged use (>5 years) and high cumulative dose (>3500 g) of metformin reduced AMD risk (P_trend = .0007).

Study details: This retrospective study included 324 patients aged ≥50 years diagnosed with T2D for ≥10 years, of which 209 were metformin users and 115 were metformin nonusers.

Disclosures: This study was funded by Hospital Youth Research Fund of China-Japan

Friendship Hospital and Beijing University of Chemical Technology-China-Japan Friendship Hospital Biomedical Translational Engineering Research Center Joint Fund. The authors declared no competing interests.

Source: Jiang J et al. Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: A retrospective study. BMJ Open. 2022;12:e054420 (Apr 26). Doi: 10.1136/bmjopen-2021-054420

Key clinical point: Patients with first-ever stroke and type 2 diabetes mellitus (T2D) who receive metformin treatment (MT) show lower stroke severity, case fatality, and disability rates.

Major finding: MT vs non-MT group had a lower rate of in-hospital case fatality (odds ratio [OR] 0.63; 95% CI 0.47-0.84), 12-month case fatality (OR 0.69; 95% CI 0.50-0.88), and 12-month disability (OR 0.83; 95% CI 0.70-0.95).

Study details: The data come from a prospective, hospital-based cohort study including 7587 patients with first-ever stroke and T2D, of which 3593 (47.36%) received MT (MT group) and 3994 (52.64%) did not receive MT (non-MT group).

Disclosures: This study was supported by the National Major Public Health Service Projects, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Natural Science Foundation of Tianjin, and China Postdoctoral Science Foundation, among others. The authors declared no conflicts of interest.

Source: Tu WJ et al. Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes. Ther Adv Chronic Dis. 2022 (Apr 19). Doi: 10.1177/20406223221076894

Key clinical point: Patients with first-ever stroke and type 2 diabetes mellitus (T2D) who receive metformin treatment (MT) show lower stroke severity, case fatality, and disability rates.

Major finding: MT vs non-MT group had a lower rate of in-hospital case fatality (odds ratio [OR] 0.63; 95% CI 0.47-0.84), 12-month case fatality (OR 0.69; 95% CI 0.50-0.88), and 12-month disability (OR 0.83; 95% CI 0.70-0.95).

Study details: The data come from a prospective, hospital-based cohort study including 7587 patients with first-ever stroke and T2D, of which 3593 (47.36%) received MT (MT group) and 3994 (52.64%) did not receive MT (non-MT group).

Disclosures: This study was supported by the National Major Public Health Service Projects, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Natural Science Foundation of Tianjin, and China Postdoctoral Science Foundation, among others. The authors declared no conflicts of interest.

Source: Tu WJ et al. Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes. Ther Adv Chronic Dis. 2022 (Apr 19). Doi: 10.1177/20406223221076894

Key clinical point: Patients with first-ever stroke and type 2 diabetes mellitus (T2D) who receive metformin treatment (MT) show lower stroke severity, case fatality, and disability rates.

Major finding: MT vs non-MT group had a lower rate of in-hospital case fatality (odds ratio [OR] 0.63; 95% CI 0.47-0.84), 12-month case fatality (OR 0.69; 95% CI 0.50-0.88), and 12-month disability (OR 0.83; 95% CI 0.70-0.95).

Study details: The data come from a prospective, hospital-based cohort study including 7587 patients with first-ever stroke and T2D, of which 3593 (47.36%) received MT (MT group) and 3994 (52.64%) did not receive MT (non-MT group).

Disclosures: This study was supported by the National Major Public Health Service Projects, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Natural Science Foundation of Tianjin, and China Postdoctoral Science Foundation, among others. The authors declared no conflicts of interest.

Source: Tu WJ et al. Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes. Ther Adv Chronic Dis. 2022 (Apr 19). Doi: 10.1177/20406223221076894

Key clinical point: Body weight gain and loss are significantly associated with a higher risk for hip fracture in patients with type 2 diabetes (T2D), irrespective of the body mass index.

Major finding: Compared with stable weight, body weight loss of ≥10% (adjusted hazard ratio [aHR] 1.605; 95% CI 1.493-1.725) and 5%-10% (aHR 1.237; 95% CI 1.177-1.300) and gain of ≥10% (aHR 1.457; 95% CI 1.318-1.612) and 5%-≤10% (aHR 1.234; 95% CI 1.156-1.318) were associated with a higher risk for hip fracture.

Study details: Findings are from a nationwide cohort study including 1,447,579 patients aged >40 years with T2D who reported 11,848 hip fracture events.

Disclosures: The study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Lee SW et al. Weight change and the risk of hip fractures in patients with type 2 diabetes: A nationwide cohort study. Osteoporos Int. 2022 (Apr 19). Doi: 10.1007/s00198-022-06398-8

Key clinical point: Body weight gain and loss are significantly associated with a higher risk for hip fracture in patients with type 2 diabetes (T2D), irrespective of the body mass index.

Major finding: Compared with stable weight, body weight loss of ≥10% (adjusted hazard ratio [aHR] 1.605; 95% CI 1.493-1.725) and 5%-10% (aHR 1.237; 95% CI 1.177-1.300) and gain of ≥10% (aHR 1.457; 95% CI 1.318-1.612) and 5%-≤10% (aHR 1.234; 95% CI 1.156-1.318) were associated with a higher risk for hip fracture.

Study details: Findings are from a nationwide cohort study including 1,447,579 patients aged >40 years with T2D who reported 11,848 hip fracture events.

Disclosures: The study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Lee SW et al. Weight change and the risk of hip fractures in patients with type 2 diabetes: A nationwide cohort study. Osteoporos Int. 2022 (Apr 19). Doi: 10.1007/s00198-022-06398-8

Key clinical point: Body weight gain and loss are significantly associated with a higher risk for hip fracture in patients with type 2 diabetes (T2D), irrespective of the body mass index.

Major finding: Compared with stable weight, body weight loss of ≥10% (adjusted hazard ratio [aHR] 1.605; 95% CI 1.493-1.725) and 5%-10% (aHR 1.237; 95% CI 1.177-1.300) and gain of ≥10% (aHR 1.457; 95% CI 1.318-1.612) and 5%-≤10% (aHR 1.234; 95% CI 1.156-1.318) were associated with a higher risk for hip fracture.

Study details: Findings are from a nationwide cohort study including 1,447,579 patients aged >40 years with T2D who reported 11,848 hip fracture events.

Disclosures: The study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Lee SW et al. Weight change and the risk of hip fractures in patients with type 2 diabetes: A nationwide cohort study. Osteoporos Int. 2022 (Apr 19). Doi: 10.1007/s00198-022-06398-8