Diabetes

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.

Contemporary cohort of patients

“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

• Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
• Stroke (HR, 0.71; 95% CI, 0.65-0.79)
• New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
• Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)

Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

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

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.

Contemporary cohort of patients

“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

• Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
• Stroke (HR, 0.71; 95% CI, 0.65-0.79)
• New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
• Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)

Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

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

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.

Contemporary cohort of patients

“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

• Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
• Stroke (HR, 0.71; 95% CI, 0.65-0.79)
• New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
• Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)

Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

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

A scientific analysis of metabolites from plant-based-diets – especially those rich in whole grains, fruits, and vegetables – may in the future yield clues as to how such eating patterns lower the risk of type 2 diabetes, finds a new study of more than 8,000 people.

The research looked at healthy, unhealthy, and overall plant-based diets, but only metabolic profiles for the healthy and overall plant-based diets showed an inverse relationship with type 2 diabetes.

Lisovskaya/iStock/Getty Images Plus

A primarily “unhealthy” plant-based diet was one including mainly refined grains (e.g., white bread and pasta), fruit juices, potatoes, sugar-sweetened beverages, and sweets/desserts.

“Individual metabolites from consumption of polyphenol-rich plant foods like fruits, vegetables, coffee, and legumes are all closely linked to healthy plant-based diet and lower risk of diabetes,” lead author Frank Hu, MD, said in a press release.

Dr. Hu, of the department of nutrition at Harvard T.H. Chan School of Public Health, Boston, and colleagues reported their findings in Diabetologia.
 

High-throughput profiling of the metabolome

Given that an individual’s metabolic profile reflects their diet, there is a growing trend in nutritional research to use a technique called high-throughput metabolomics to profile biological samples.

The team conducted an analysis of blood plasma samples and dietary intake using food frequency questionnaires of 10,684 participants from three prospective cohorts (Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-Up Study). Participants were predominantly White and middle-aged (mean age 54 years), with a mean body mass index of 25.6 kg/m².

Metabolite profile scores were generated from the blood samples, taken in the 1980s and 1990s, and matched to any cases of incident type 2 diabetes reported during follow-up, which ended in 2016-2017.

The team looked at three different plant-based diets – by definition, higher in plant foods and lower in animal foods – and further categorized them according to the actual foods consumed, to generate an overall plant diet index (PDI), a healthy PDI, or an unhealthy PDI.

In all, 8,827 participants completed the study, and 270 cases of diabetes were reported.

Multi-metabolite profiles were composed of 55 metabolites for the overall PDI, 93 metabolites for healthy PDI, and 75 metabolites for unhealthy PDI.

The findings are that metabolomics can be harnessed and “the identified metabolic profiles could be used to assess adherence to ... plant-based diets as part of type 2 diabetes prevention ... and provide new insights for future investigation,” the researchers concluded.

One coauthor received research support from the California Walnut Commission and Swiss ReManagement; another reported being a scientific consultant to LayerIV. The other authors have reported no relevant financial relationships.

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

A scientific analysis of metabolites from plant-based-diets – especially those rich in whole grains, fruits, and vegetables – may in the future yield clues as to how such eating patterns lower the risk of type 2 diabetes, finds a new study of more than 8,000 people.

The research looked at healthy, unhealthy, and overall plant-based diets, but only metabolic profiles for the healthy and overall plant-based diets showed an inverse relationship with type 2 diabetes.

Lisovskaya/iStock/Getty Images Plus

A primarily “unhealthy” plant-based diet was one including mainly refined grains (e.g., white bread and pasta), fruit juices, potatoes, sugar-sweetened beverages, and sweets/desserts.

“Individual metabolites from consumption of polyphenol-rich plant foods like fruits, vegetables, coffee, and legumes are all closely linked to healthy plant-based diet and lower risk of diabetes,” lead author Frank Hu, MD, said in a press release.

Dr. Hu, of the department of nutrition at Harvard T.H. Chan School of Public Health, Boston, and colleagues reported their findings in Diabetologia.
 

High-throughput profiling of the metabolome

Given that an individual’s metabolic profile reflects their diet, there is a growing trend in nutritional research to use a technique called high-throughput metabolomics to profile biological samples.

The team conducted an analysis of blood plasma samples and dietary intake using food frequency questionnaires of 10,684 participants from three prospective cohorts (Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-Up Study). Participants were predominantly White and middle-aged (mean age 54 years), with a mean body mass index of 25.6 kg/m².

Metabolite profile scores were generated from the blood samples, taken in the 1980s and 1990s, and matched to any cases of incident type 2 diabetes reported during follow-up, which ended in 2016-2017.

The team looked at three different plant-based diets – by definition, higher in plant foods and lower in animal foods – and further categorized them according to the actual foods consumed, to generate an overall plant diet index (PDI), a healthy PDI, or an unhealthy PDI.

In all, 8,827 participants completed the study, and 270 cases of diabetes were reported.

Multi-metabolite profiles were composed of 55 metabolites for the overall PDI, 93 metabolites for healthy PDI, and 75 metabolites for unhealthy PDI.

The findings are that metabolomics can be harnessed and “the identified metabolic profiles could be used to assess adherence to ... plant-based diets as part of type 2 diabetes prevention ... and provide new insights for future investigation,” the researchers concluded.

One coauthor received research support from the California Walnut Commission and Swiss ReManagement; another reported being a scientific consultant to LayerIV. The other authors have reported no relevant financial relationships.

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

A scientific analysis of metabolites from plant-based-diets – especially those rich in whole grains, fruits, and vegetables – may in the future yield clues as to how such eating patterns lower the risk of type 2 diabetes, finds a new study of more than 8,000 people.

The research looked at healthy, unhealthy, and overall plant-based diets, but only metabolic profiles for the healthy and overall plant-based diets showed an inverse relationship with type 2 diabetes.

Lisovskaya/iStock/Getty Images Plus

A primarily “unhealthy” plant-based diet was one including mainly refined grains (e.g., white bread and pasta), fruit juices, potatoes, sugar-sweetened beverages, and sweets/desserts.

“Individual metabolites from consumption of polyphenol-rich plant foods like fruits, vegetables, coffee, and legumes are all closely linked to healthy plant-based diet and lower risk of diabetes,” lead author Frank Hu, MD, said in a press release.

Dr. Hu, of the department of nutrition at Harvard T.H. Chan School of Public Health, Boston, and colleagues reported their findings in Diabetologia.
 

High-throughput profiling of the metabolome

Given that an individual’s metabolic profile reflects their diet, there is a growing trend in nutritional research to use a technique called high-throughput metabolomics to profile biological samples.

The team conducted an analysis of blood plasma samples and dietary intake using food frequency questionnaires of 10,684 participants from three prospective cohorts (Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-Up Study). Participants were predominantly White and middle-aged (mean age 54 years), with a mean body mass index of 25.6 kg/m².

Metabolite profile scores were generated from the blood samples, taken in the 1980s and 1990s, and matched to any cases of incident type 2 diabetes reported during follow-up, which ended in 2016-2017.

The team looked at three different plant-based diets – by definition, higher in plant foods and lower in animal foods – and further categorized them according to the actual foods consumed, to generate an overall plant diet index (PDI), a healthy PDI, or an unhealthy PDI.

In all, 8,827 participants completed the study, and 270 cases of diabetes were reported.

Multi-metabolite profiles were composed of 55 metabolites for the overall PDI, 93 metabolites for healthy PDI, and 75 metabolites for unhealthy PDI.

The findings are that metabolomics can be harnessed and “the identified metabolic profiles could be used to assess adherence to ... plant-based diets as part of type 2 diabetes prevention ... and provide new insights for future investigation,” the researchers concluded.

One coauthor received research support from the California Walnut Commission and Swiss ReManagement; another reported being a scientific consultant to LayerIV. The other authors have reported no relevant financial relationships.

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

A network meta-analysis of 42 clinical trials concludes that rosuvastatin, simvastatin, and atorvastatin are the statins most effective at lowering non-high-density-lipoprotein cholesterol (non-HDL-C) in people with diabetes and at risk for cardiovascular disease.

The analysis focused on the efficacy of statin treatment on reducing non-HDL-C, as opposed to reducing low-density-lipoprotein cholesterol (LDL-C), which has traditionally been used as a surrogate to determine cardiovascular disease risk from hypercholesterolemia.

“The National Cholesterol Education Program in the United States recommends that LDL-C values should be used to estimate the risk of cardiovascular disease related to lipoproteins,” lead author Alexander Hodkinson, MD, senior National Institute for Health Research fellow, University of Manchester, England, told this news organization.

“But we believe that non-high-density-lipoprotein cholesterol is more strongly associated with the risk of cardiovascular disease, because non-HDL-C combines all the bad types of cholesterol, which LDL-C misses, so it could be a better tool than LDL-C for assessing CVD risk and effects of treatment. We already knew which of the statins reduce LDL-C, but we wanted to know which ones reduced non-HDL-C; hence the reason for our study,” Dr. Hodkinson said.

The findings were published online  in BMJ.

In April 2021, the National Institute for Health and Care Excellence (NICE) in the United Kingdom updated guidelines for adults with diabetes to recommend that non-HDL-C should replace LDL-C as the primary target for reducing the risk for cardiovascular disease with lipid-lowering treatment.

Currently, NICE is alone in its recommendation. Other international guidelines do not have a non-HDL-C target and use LDL-C reduction instead. These include guidelines from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association.

Non–HDL-C is simple to calculate and can easily be done by clinicians by subtracting HDL-C from the total cholesterol level, he added.

This analysis compared the effectiveness of different statins at different intensities in reducing levels of non-HDL-C in 42 randomized controlled trials that included 20,193 adults with diabetes.

Compared with placebo, rosuvastatin, given at moderate- and high-intensity doses, and simvastatin and atorvastatin at high-intensity doses, were the best at lowering levels of non-HDL-C over an average treatment period of 12 weeks.

High-intensity rosuvastatin led to a 2.31 mmol/L reduction in non-HDL-C (95% credible interval, –3.39 to –1.21). Moderate-intensity rosuvastatin led to a 2.27 mmol/L reduction in non-HDL-C (95% credible interval, –3.00 to –1.49).

High-intensity simvastatin led to a 2.26 mmol/L reduction in non-HDL-C (95% credible interval, –2.99 to –1.51).

High-intensity atorvastatin led to a 2.20 mmol/L reduction in non-HDL-C (95% credible interval, –2.69 to –1.70).

Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C, the researchers noted.

In 4,670 patients who were at great risk for a major cardiovascular event, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98 mmol/L; 95% credible interval, –4.16 to 0.26).

In addition, high-intensity simvastatin and rosuvastatin were the most effective in reducing LDL-C.

High-intensity simvastatin led to a 1.93 mmol/L reduction in LDL-C (95% credible interval, –2.63 to –1.21), and high-intensity rosuvastatin led to a 1.76 mmol/L reduction in LDL-C (95% credible interval, –2.37 to –1.15).

In four studies, significant reductions in nonfatal myocardial infarction were shown for atorvastatin at moderate intensity, compared with placebo (relative risk, 0.57; 95% confidence interval, 0.43-.76). No significant differences were seen for discontinuations, nonfatal stroke, or cardiovascular death.

“We hope our findings will help guide clinicians on statin selection itself, and what types of doses they should be giving patients. These results support using NICE’s new policy guidelines on cholesterol monitoring, using this non-HDL-C measure, which contains all the bad types of cholesterol for patients with diabetes,” Dr. Hodkinson said.

“This study further emphasizes what we have known about the benefit of statin therapy in patients with type 2 diabetes,” Prakash Deedwania, MD, professor of medicine, University of California, San Francisco, told this news organization.

Dr. Deedwania and others have published data on patients with diabetes that showed that treatment with high-intensity atorvastatin was associated with significant reductions in major adverse cardiovascular events.

“Here they use non-HDL cholesterol as a target. The NICE guidelines are the only guidelines looking at non-HDL cholesterol; however, all guidelines suggest an LDL to be less than 70 in all people with diabetes, and for those with recent acute coronary syndromes, the latest evidence suggests the LDL should actually be less than 50,” said Dr. Deedwania, spokesperson for the AHA and ACC.

As far as which measure to use, he believes both are useful. “It’s six of one and half a dozen of the other, in my opinion. The societies have not recommended non-HDL cholesterol and it’s easier to stay with what is readily available for clinicians, and using LDL cholesterol is still okay. The results of this analysis are confirmatory, in that looking at non-HDL cholesterol gives results very similar to what these statins have shown for their effect on LDL cholesterol,” he said.
 

Non-HDL cholesterol a better marker?

For Robert Rosenson, MD, director of metabolism and lipids at Mount Sinai Health System and professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai, New York, non-HDL cholesterol is becoming an important marker of risk for several reasons.

“The focus on LDL cholesterol has been due to the causal relationship of LDL with atherosclerotic cardiovascular disease, but in the last few decades, non-HDL has emerged because more people are overweight, have insulin resistance, and have diabetes,” Dr. Rosenson told this news organization. “In those situations, the LDL cholesterol underrepresents the risk of the LDL particles. With insulin resistance, the particles become more triglycerides and less cholesterol, so on a per-particle basis, you need to get more LDL particles to get to a certain LDL cholesterol concentration.”

Non-HDL cholesterol testing does not require fasting, another advantage of using it to monitor cholesterol, he added.

What is often forgotten is that moderate- to high-intensity statins have very good triglyceride-lowering effects, Dr. Rosenson said.

“This article highlights that, by using higher doses, you get more triglyceride-lowering. Hopefully, this will get practitioners to recognize that non-HDL cholesterol is a better predictor of risk in people with diabetes,” he said.

The study was funded by the National Institute for Health Research. Dr. Hodkinson, Dr. Rosenson, and Dr. Deedwania report no relevant financial relationships.

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

A network meta-analysis of 42 clinical trials concludes that rosuvastatin, simvastatin, and atorvastatin are the statins most effective at lowering non-high-density-lipoprotein cholesterol (non-HDL-C) in people with diabetes and at risk for cardiovascular disease.

The analysis focused on the efficacy of statin treatment on reducing non-HDL-C, as opposed to reducing low-density-lipoprotein cholesterol (LDL-C), which has traditionally been used as a surrogate to determine cardiovascular disease risk from hypercholesterolemia.

“The National Cholesterol Education Program in the United States recommends that LDL-C values should be used to estimate the risk of cardiovascular disease related to lipoproteins,” lead author Alexander Hodkinson, MD, senior National Institute for Health Research fellow, University of Manchester, England, told this news organization.

“But we believe that non-high-density-lipoprotein cholesterol is more strongly associated with the risk of cardiovascular disease, because non-HDL-C combines all the bad types of cholesterol, which LDL-C misses, so it could be a better tool than LDL-C for assessing CVD risk and effects of treatment. We already knew which of the statins reduce LDL-C, but we wanted to know which ones reduced non-HDL-C; hence the reason for our study,” Dr. Hodkinson said.

The findings were published online  in BMJ.

In April 2021, the National Institute for Health and Care Excellence (NICE) in the United Kingdom updated guidelines for adults with diabetes to recommend that non-HDL-C should replace LDL-C as the primary target for reducing the risk for cardiovascular disease with lipid-lowering treatment.

Currently, NICE is alone in its recommendation. Other international guidelines do not have a non-HDL-C target and use LDL-C reduction instead. These include guidelines from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association.

Non–HDL-C is simple to calculate and can easily be done by clinicians by subtracting HDL-C from the total cholesterol level, he added.

This analysis compared the effectiveness of different statins at different intensities in reducing levels of non-HDL-C in 42 randomized controlled trials that included 20,193 adults with diabetes.

Compared with placebo, rosuvastatin, given at moderate- and high-intensity doses, and simvastatin and atorvastatin at high-intensity doses, were the best at lowering levels of non-HDL-C over an average treatment period of 12 weeks.

High-intensity rosuvastatin led to a 2.31 mmol/L reduction in non-HDL-C (95% credible interval, –3.39 to –1.21). Moderate-intensity rosuvastatin led to a 2.27 mmol/L reduction in non-HDL-C (95% credible interval, –3.00 to –1.49).

High-intensity simvastatin led to a 2.26 mmol/L reduction in non-HDL-C (95% credible interval, –2.99 to –1.51).

High-intensity atorvastatin led to a 2.20 mmol/L reduction in non-HDL-C (95% credible interval, –2.69 to –1.70).

Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C, the researchers noted.

In 4,670 patients who were at great risk for a major cardiovascular event, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98 mmol/L; 95% credible interval, –4.16 to 0.26).

In addition, high-intensity simvastatin and rosuvastatin were the most effective in reducing LDL-C.

High-intensity simvastatin led to a 1.93 mmol/L reduction in LDL-C (95% credible interval, –2.63 to –1.21), and high-intensity rosuvastatin led to a 1.76 mmol/L reduction in LDL-C (95% credible interval, –2.37 to –1.15).

In four studies, significant reductions in nonfatal myocardial infarction were shown for atorvastatin at moderate intensity, compared with placebo (relative risk, 0.57; 95% confidence interval, 0.43-.76). No significant differences were seen for discontinuations, nonfatal stroke, or cardiovascular death.

“We hope our findings will help guide clinicians on statin selection itself, and what types of doses they should be giving patients. These results support using NICE’s new policy guidelines on cholesterol monitoring, using this non-HDL-C measure, which contains all the bad types of cholesterol for patients with diabetes,” Dr. Hodkinson said.

“This study further emphasizes what we have known about the benefit of statin therapy in patients with type 2 diabetes,” Prakash Deedwania, MD, professor of medicine, University of California, San Francisco, told this news organization.

Dr. Deedwania and others have published data on patients with diabetes that showed that treatment with high-intensity atorvastatin was associated with significant reductions in major adverse cardiovascular events.

“Here they use non-HDL cholesterol as a target. The NICE guidelines are the only guidelines looking at non-HDL cholesterol; however, all guidelines suggest an LDL to be less than 70 in all people with diabetes, and for those with recent acute coronary syndromes, the latest evidence suggests the LDL should actually be less than 50,” said Dr. Deedwania, spokesperson for the AHA and ACC.

As far as which measure to use, he believes both are useful. “It’s six of one and half a dozen of the other, in my opinion. The societies have not recommended non-HDL cholesterol and it’s easier to stay with what is readily available for clinicians, and using LDL cholesterol is still okay. The results of this analysis are confirmatory, in that looking at non-HDL cholesterol gives results very similar to what these statins have shown for their effect on LDL cholesterol,” he said.
 

Non-HDL cholesterol a better marker?

For Robert Rosenson, MD, director of metabolism and lipids at Mount Sinai Health System and professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai, New York, non-HDL cholesterol is becoming an important marker of risk for several reasons.

“The focus on LDL cholesterol has been due to the causal relationship of LDL with atherosclerotic cardiovascular disease, but in the last few decades, non-HDL has emerged because more people are overweight, have insulin resistance, and have diabetes,” Dr. Rosenson told this news organization. “In those situations, the LDL cholesterol underrepresents the risk of the LDL particles. With insulin resistance, the particles become more triglycerides and less cholesterol, so on a per-particle basis, you need to get more LDL particles to get to a certain LDL cholesterol concentration.”

Non-HDL cholesterol testing does not require fasting, another advantage of using it to monitor cholesterol, he added.

What is often forgotten is that moderate- to high-intensity statins have very good triglyceride-lowering effects, Dr. Rosenson said.

“This article highlights that, by using higher doses, you get more triglyceride-lowering. Hopefully, this will get practitioners to recognize that non-HDL cholesterol is a better predictor of risk in people with diabetes,” he said.

The study was funded by the National Institute for Health Research. Dr. Hodkinson, Dr. Rosenson, and Dr. Deedwania report no relevant financial relationships.

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

A network meta-analysis of 42 clinical trials concludes that rosuvastatin, simvastatin, and atorvastatin are the statins most effective at lowering non-high-density-lipoprotein cholesterol (non-HDL-C) in people with diabetes and at risk for cardiovascular disease.

The analysis focused on the efficacy of statin treatment on reducing non-HDL-C, as opposed to reducing low-density-lipoprotein cholesterol (LDL-C), which has traditionally been used as a surrogate to determine cardiovascular disease risk from hypercholesterolemia.

“The National Cholesterol Education Program in the United States recommends that LDL-C values should be used to estimate the risk of cardiovascular disease related to lipoproteins,” lead author Alexander Hodkinson, MD, senior National Institute for Health Research fellow, University of Manchester, England, told this news organization.

“But we believe that non-high-density-lipoprotein cholesterol is more strongly associated with the risk of cardiovascular disease, because non-HDL-C combines all the bad types of cholesterol, which LDL-C misses, so it could be a better tool than LDL-C for assessing CVD risk and effects of treatment. We already knew which of the statins reduce LDL-C, but we wanted to know which ones reduced non-HDL-C; hence the reason for our study,” Dr. Hodkinson said.

The findings were published online  in BMJ.

In April 2021, the National Institute for Health and Care Excellence (NICE) in the United Kingdom updated guidelines for adults with diabetes to recommend that non-HDL-C should replace LDL-C as the primary target for reducing the risk for cardiovascular disease with lipid-lowering treatment.

Currently, NICE is alone in its recommendation. Other international guidelines do not have a non-HDL-C target and use LDL-C reduction instead. These include guidelines from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association.

Non–HDL-C is simple to calculate and can easily be done by clinicians by subtracting HDL-C from the total cholesterol level, he added.

This analysis compared the effectiveness of different statins at different intensities in reducing levels of non-HDL-C in 42 randomized controlled trials that included 20,193 adults with diabetes.

Compared with placebo, rosuvastatin, given at moderate- and high-intensity doses, and simvastatin and atorvastatin at high-intensity doses, were the best at lowering levels of non-HDL-C over an average treatment period of 12 weeks.

High-intensity rosuvastatin led to a 2.31 mmol/L reduction in non-HDL-C (95% credible interval, –3.39 to –1.21). Moderate-intensity rosuvastatin led to a 2.27 mmol/L reduction in non-HDL-C (95% credible interval, –3.00 to –1.49).

High-intensity simvastatin led to a 2.26 mmol/L reduction in non-HDL-C (95% credible interval, –2.99 to –1.51).

High-intensity atorvastatin led to a 2.20 mmol/L reduction in non-HDL-C (95% credible interval, –2.69 to –1.70).

Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C, the researchers noted.

In 4,670 patients who were at great risk for a major cardiovascular event, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98 mmol/L; 95% credible interval, –4.16 to 0.26).

In addition, high-intensity simvastatin and rosuvastatin were the most effective in reducing LDL-C.

High-intensity simvastatin led to a 1.93 mmol/L reduction in LDL-C (95% credible interval, –2.63 to –1.21), and high-intensity rosuvastatin led to a 1.76 mmol/L reduction in LDL-C (95% credible interval, –2.37 to –1.15).

In four studies, significant reductions in nonfatal myocardial infarction were shown for atorvastatin at moderate intensity, compared with placebo (relative risk, 0.57; 95% confidence interval, 0.43-.76). No significant differences were seen for discontinuations, nonfatal stroke, or cardiovascular death.

“We hope our findings will help guide clinicians on statin selection itself, and what types of doses they should be giving patients. These results support using NICE’s new policy guidelines on cholesterol monitoring, using this non-HDL-C measure, which contains all the bad types of cholesterol for patients with diabetes,” Dr. Hodkinson said.

“This study further emphasizes what we have known about the benefit of statin therapy in patients with type 2 diabetes,” Prakash Deedwania, MD, professor of medicine, University of California, San Francisco, told this news organization.

Dr. Deedwania and others have published data on patients with diabetes that showed that treatment with high-intensity atorvastatin was associated with significant reductions in major adverse cardiovascular events.

“Here they use non-HDL cholesterol as a target. The NICE guidelines are the only guidelines looking at non-HDL cholesterol; however, all guidelines suggest an LDL to be less than 70 in all people with diabetes, and for those with recent acute coronary syndromes, the latest evidence suggests the LDL should actually be less than 50,” said Dr. Deedwania, spokesperson for the AHA and ACC.

As far as which measure to use, he believes both are useful. “It’s six of one and half a dozen of the other, in my opinion. The societies have not recommended non-HDL cholesterol and it’s easier to stay with what is readily available for clinicians, and using LDL cholesterol is still okay. The results of this analysis are confirmatory, in that looking at non-HDL cholesterol gives results very similar to what these statins have shown for their effect on LDL cholesterol,” he said.
 

Non-HDL cholesterol a better marker?

For Robert Rosenson, MD, director of metabolism and lipids at Mount Sinai Health System and professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai, New York, non-HDL cholesterol is becoming an important marker of risk for several reasons.

“The focus on LDL cholesterol has been due to the causal relationship of LDL with atherosclerotic cardiovascular disease, but in the last few decades, non-HDL has emerged because more people are overweight, have insulin resistance, and have diabetes,” Dr. Rosenson told this news organization. “In those situations, the LDL cholesterol underrepresents the risk of the LDL particles. With insulin resistance, the particles become more triglycerides and less cholesterol, so on a per-particle basis, you need to get more LDL particles to get to a certain LDL cholesterol concentration.”

Non-HDL cholesterol testing does not require fasting, another advantage of using it to monitor cholesterol, he added.

What is often forgotten is that moderate- to high-intensity statins have very good triglyceride-lowering effects, Dr. Rosenson said.

“This article highlights that, by using higher doses, you get more triglyceride-lowering. Hopefully, this will get practitioners to recognize that non-HDL cholesterol is a better predictor of risk in people with diabetes,” he said.

The study was funded by the National Institute for Health Research. Dr. Hodkinson, Dr. Rosenson, and Dr. Deedwania report no relevant financial relationships.

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

WASHINGTON – Patients with type 2 diabetes and established atherosclerotic cardiovascular disease treated with both an sodium-glucose transporter 2 inhibitor and a glucagonlike peptide–1 receptor agonist had a significant 80% cut in their rate of all-cause death during 1-year follow-up, compared with matched patients treated with an agent from either class alone in an observational, retrospective study of more than 15,000 people in the U.S. Veterans Affairs health system.

For the study’s primary endpoint, the combined rate of all-cause death, nonfatal MI, or nonfatal stroke, combined treatment with both an agent from the sodium-glucose transporter 2 (SGLT2) inhibitor class and from the glucagonlike peptide–1 receptor agonist (GLP-1 RA) class linked with a significant, roughly 50% cut in events during 1-year follow-up, compared with patients treated with an agent from just one of these two classes, Persio D. Lopez, MD, reported at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

This improvement in the combined endpoint outcome resulted entirely from reduced all-cause mortality. Dual treatment showed no significant association with the incidence of nonfatal MIs or strokes, compared with monotherapy, with rates that were nearly identical regardless of whether patients took one of the agents or both, said Dr. Lopez, a cardiologist at Mount Sinai Morningside and the James J. Peters VA Medical Center, both in New York.
 

Combining classes for hard-to-control diabetes

“We’re not sure what drives combined use” of agents from both drug classes in these types of patients, admitted Dr. Lopez during his talk. “Our hypothesis is that dual treatment is used in patients with harder-to-control diabetes.”

Salim S. Virani, MD, PhD, who practices in the VA system but was not involved with the study, agreed that this is the likely explanation for most instances of high-risk VA patients with diabetes who receive agents from both classes.

Mitchel L. Zoler/MDedge News

“I have a few patients” on both classes, usually “patients with higher starting A1c levels who need greater glycemic control,” said Dr. Virani, professor of medicine at Baylor College of Medicine and a cardiologist at the Michael E. DeBakey VA Medical Center, both in Houston.

U.S. use of either drug class, let alone both, in patients with type 2 diabetes is still struggling to gain traction in U.S. practice and remains limited to a minority of these patients, a prescribing pattern reflected in recent VA data. Analysis of more than half a million patients in the VA system with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who received treatment at any of 130 VA medical centers throughout 2020 showed that 11% had received an SGLT2 inhibitor, and 8% a GLP-1 RA.

The most frequently used antidiabetes drug classes in these patients were insulin in 36%, biguanides in 47%, and sulfonylureas in 22%.

These data also showed a striking level of variability among the 130 VA centers, with some of the sites prescribing either an SGLT2 inhibitor or a GLP-1 RA to as few as about 3% each of these patients, while other centers had a roughly 10-fold higher prescription rate for each of about 25%-30% of their patients with type 2 diabetes and ASCVD.

Despite the overall modest level of use of both classes in these types of patients as recently as 2020, no barriers exist at the VA to prescribing an agent from one or both classes “if you provide a good reason” for a patient to receive the drugs, Dr. Virani said in an interview. He also predicted that use of both classes in these patients, including combination treatment, will likely soon expand.
 

‘A lot of interest’ in combining an SGLT2 inhibitor and a GLP-1 RA

“There will be a lot of interest in combing the two classes. It makes intuitive sense [to treat with both classes] because most patients with diabetes need more than one drug” for glycemic control, he noted. “Why not use two classes that each reduce a patient’s risk” for adverse outcomes involving ASCVD, heart failure, and renal dysfunction, added Dr. Virani.

The study run by Dr. Lopez and his associates used data collected in the National VA Database and included 121,156 patients with both type 2 diabetes and established ASCVD. Using propensity-score matching the researchers compiled three subgroups that each included 5,277 matched patients. One subgroup had patients prescribed an SGLT2 inhibitor, a second subgroup included patients on a GLP-1 RA, and a third subgroup had patients on agents from both classes. Patient matching relied on age, sex, left ventricular ejection fraction, hemoglobin A1c level, systolic blood pressure, and the presence of coronary artery disease or peripheral artery disease.

Patients included in the analysis averaged about 67 years of age; 97% were men, their average body mass index was about 34 kg/m², their average A1c was about 7.9%, their average estimated glomerular filtration rate was about 55-66 mL/min per 1.73 m², and their average left ventricular ejection fraction was about 55%. The database provided a median follow-up of 902 days (about 2.5 years). The prespecified primary endpoint focused on events that occurred during the first year of follow-up, but the investigators also ran a 3-year follow-up analysis on a post hoc basis.

The most common SGLT2 inhibitor received by these patients was empagliflozin (Jardiance), used on virtually everyone who received an agent from this class. In contrast, the GLP-1 RA drugs that patients received split more widely. The most prescribed agent was liraglutide (Victoza), followed by semaglutide (Ozempic), and dulaglutide (Trulicity), with fewer than 5% receiving exenatide (Bydureon, Byetta).

Regarding other treatments, about 97% of all patients received a statin, about 94% were on a renin-angiotensin system inhibitor, about 90% were on metformin, and roughly 75% were on insulin, aspirin, and a beta-blocker, with smaller numbers on other types of agents.

For the study’s primary endpoint, the 1-year incidence of combined ASCVD events including all-cause death, patients on agents from both classes had a significant 46% reduced rate compared with those on an SGLT2 inhibitor only, and a significant 49% reduced rate, compared with those on a GLP-1 RA only. These between-group separations broadened slightly during 3-year follow-up. Dr. Lopez did not report results of a direct comparison between patients on just an SGLT2 inhibitor and those on just a GLP-1 RA.

For the endpoint of all-cause death, those on combined treatment had a 1-year rate that was 83% below the rate among patients on only an SGLT2 inhibitor, and 81% below the rate among patients who received a GLP-1 RA but not the other class.

Dr. Lopez cautioned that selection bias could have influenced the outcomes of patients who received both classes rather than one or the other, and he also highlighted that the analysis relied on administrative data rather than information gleaned from more detailed medical records or prospectively collected findings and was limited by only including a very small number of women.

“Our results need to be validated in prospective studies,” he declared.

Dr. Lopez and Dr. Virani had no commercial disclosures.

WASHINGTON – Patients with type 2 diabetes and established atherosclerotic cardiovascular disease treated with both an sodium-glucose transporter 2 inhibitor and a glucagonlike peptide–1 receptor agonist had a significant 80% cut in their rate of all-cause death during 1-year follow-up, compared with matched patients treated with an agent from either class alone in an observational, retrospective study of more than 15,000 people in the U.S. Veterans Affairs health system.

For the study’s primary endpoint, the combined rate of all-cause death, nonfatal MI, or nonfatal stroke, combined treatment with both an agent from the sodium-glucose transporter 2 (SGLT2) inhibitor class and from the glucagonlike peptide–1 receptor agonist (GLP-1 RA) class linked with a significant, roughly 50% cut in events during 1-year follow-up, compared with patients treated with an agent from just one of these two classes, Persio D. Lopez, MD, reported at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

This improvement in the combined endpoint outcome resulted entirely from reduced all-cause mortality. Dual treatment showed no significant association with the incidence of nonfatal MIs or strokes, compared with monotherapy, with rates that were nearly identical regardless of whether patients took one of the agents or both, said Dr. Lopez, a cardiologist at Mount Sinai Morningside and the James J. Peters VA Medical Center, both in New York.
 

Combining classes for hard-to-control diabetes

“We’re not sure what drives combined use” of agents from both drug classes in these types of patients, admitted Dr. Lopez during his talk. “Our hypothesis is that dual treatment is used in patients with harder-to-control diabetes.”

Salim S. Virani, MD, PhD, who practices in the VA system but was not involved with the study, agreed that this is the likely explanation for most instances of high-risk VA patients with diabetes who receive agents from both classes.

Mitchel L. Zoler/MDedge News

“I have a few patients” on both classes, usually “patients with higher starting A1c levels who need greater glycemic control,” said Dr. Virani, professor of medicine at Baylor College of Medicine and a cardiologist at the Michael E. DeBakey VA Medical Center, both in Houston.

U.S. use of either drug class, let alone both, in patients with type 2 diabetes is still struggling to gain traction in U.S. practice and remains limited to a minority of these patients, a prescribing pattern reflected in recent VA data. Analysis of more than half a million patients in the VA system with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who received treatment at any of 130 VA medical centers throughout 2020 showed that 11% had received an SGLT2 inhibitor, and 8% a GLP-1 RA.

The most frequently used antidiabetes drug classes in these patients were insulin in 36%, biguanides in 47%, and sulfonylureas in 22%.

These data also showed a striking level of variability among the 130 VA centers, with some of the sites prescribing either an SGLT2 inhibitor or a GLP-1 RA to as few as about 3% each of these patients, while other centers had a roughly 10-fold higher prescription rate for each of about 25%-30% of their patients with type 2 diabetes and ASCVD.

Despite the overall modest level of use of both classes in these types of patients as recently as 2020, no barriers exist at the VA to prescribing an agent from one or both classes “if you provide a good reason” for a patient to receive the drugs, Dr. Virani said in an interview. He also predicted that use of both classes in these patients, including combination treatment, will likely soon expand.
 

‘A lot of interest’ in combining an SGLT2 inhibitor and a GLP-1 RA

“There will be a lot of interest in combing the two classes. It makes intuitive sense [to treat with both classes] because most patients with diabetes need more than one drug” for glycemic control, he noted. “Why not use two classes that each reduce a patient’s risk” for adverse outcomes involving ASCVD, heart failure, and renal dysfunction, added Dr. Virani.

The study run by Dr. Lopez and his associates used data collected in the National VA Database and included 121,156 patients with both type 2 diabetes and established ASCVD. Using propensity-score matching the researchers compiled three subgroups that each included 5,277 matched patients. One subgroup had patients prescribed an SGLT2 inhibitor, a second subgroup included patients on a GLP-1 RA, and a third subgroup had patients on agents from both classes. Patient matching relied on age, sex, left ventricular ejection fraction, hemoglobin A1c level, systolic blood pressure, and the presence of coronary artery disease or peripheral artery disease.

Patients included in the analysis averaged about 67 years of age; 97% were men, their average body mass index was about 34 kg/m², their average A1c was about 7.9%, their average estimated glomerular filtration rate was about 55-66 mL/min per 1.73 m², and their average left ventricular ejection fraction was about 55%. The database provided a median follow-up of 902 days (about 2.5 years). The prespecified primary endpoint focused on events that occurred during the first year of follow-up, but the investigators also ran a 3-year follow-up analysis on a post hoc basis.

The most common SGLT2 inhibitor received by these patients was empagliflozin (Jardiance), used on virtually everyone who received an agent from this class. In contrast, the GLP-1 RA drugs that patients received split more widely. The most prescribed agent was liraglutide (Victoza), followed by semaglutide (Ozempic), and dulaglutide (Trulicity), with fewer than 5% receiving exenatide (Bydureon, Byetta).

Regarding other treatments, about 97% of all patients received a statin, about 94% were on a renin-angiotensin system inhibitor, about 90% were on metformin, and roughly 75% were on insulin, aspirin, and a beta-blocker, with smaller numbers on other types of agents.

For the study’s primary endpoint, the 1-year incidence of combined ASCVD events including all-cause death, patients on agents from both classes had a significant 46% reduced rate compared with those on an SGLT2 inhibitor only, and a significant 49% reduced rate, compared with those on a GLP-1 RA only. These between-group separations broadened slightly during 3-year follow-up. Dr. Lopez did not report results of a direct comparison between patients on just an SGLT2 inhibitor and those on just a GLP-1 RA.

For the endpoint of all-cause death, those on combined treatment had a 1-year rate that was 83% below the rate among patients on only an SGLT2 inhibitor, and 81% below the rate among patients who received a GLP-1 RA but not the other class.

Dr. Lopez cautioned that selection bias could have influenced the outcomes of patients who received both classes rather than one or the other, and he also highlighted that the analysis relied on administrative data rather than information gleaned from more detailed medical records or prospectively collected findings and was limited by only including a very small number of women.

“Our results need to be validated in prospective studies,” he declared.

Dr. Lopez and Dr. Virani had no commercial disclosures.

WASHINGTON – Patients with type 2 diabetes and established atherosclerotic cardiovascular disease treated with both an sodium-glucose transporter 2 inhibitor and a glucagonlike peptide–1 receptor agonist had a significant 80% cut in their rate of all-cause death during 1-year follow-up, compared with matched patients treated with an agent from either class alone in an observational, retrospective study of more than 15,000 people in the U.S. Veterans Affairs health system.

For the study’s primary endpoint, the combined rate of all-cause death, nonfatal MI, or nonfatal stroke, combined treatment with both an agent from the sodium-glucose transporter 2 (SGLT2) inhibitor class and from the glucagonlike peptide–1 receptor agonist (GLP-1 RA) class linked with a significant, roughly 50% cut in events during 1-year follow-up, compared with patients treated with an agent from just one of these two classes, Persio D. Lopez, MD, reported at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

This improvement in the combined endpoint outcome resulted entirely from reduced all-cause mortality. Dual treatment showed no significant association with the incidence of nonfatal MIs or strokes, compared with monotherapy, with rates that were nearly identical regardless of whether patients took one of the agents or both, said Dr. Lopez, a cardiologist at Mount Sinai Morningside and the James J. Peters VA Medical Center, both in New York.
 

Combining classes for hard-to-control diabetes

“We’re not sure what drives combined use” of agents from both drug classes in these types of patients, admitted Dr. Lopez during his talk. “Our hypothesis is that dual treatment is used in patients with harder-to-control diabetes.”

Salim S. Virani, MD, PhD, who practices in the VA system but was not involved with the study, agreed that this is the likely explanation for most instances of high-risk VA patients with diabetes who receive agents from both classes.

Mitchel L. Zoler/MDedge News

“I have a few patients” on both classes, usually “patients with higher starting A1c levels who need greater glycemic control,” said Dr. Virani, professor of medicine at Baylor College of Medicine and a cardiologist at the Michael E. DeBakey VA Medical Center, both in Houston.

U.S. use of either drug class, let alone both, in patients with type 2 diabetes is still struggling to gain traction in U.S. practice and remains limited to a minority of these patients, a prescribing pattern reflected in recent VA data. Analysis of more than half a million patients in the VA system with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who received treatment at any of 130 VA medical centers throughout 2020 showed that 11% had received an SGLT2 inhibitor, and 8% a GLP-1 RA.

The most frequently used antidiabetes drug classes in these patients were insulin in 36%, biguanides in 47%, and sulfonylureas in 22%.

These data also showed a striking level of variability among the 130 VA centers, with some of the sites prescribing either an SGLT2 inhibitor or a GLP-1 RA to as few as about 3% each of these patients, while other centers had a roughly 10-fold higher prescription rate for each of about 25%-30% of their patients with type 2 diabetes and ASCVD.

Despite the overall modest level of use of both classes in these types of patients as recently as 2020, no barriers exist at the VA to prescribing an agent from one or both classes “if you provide a good reason” for a patient to receive the drugs, Dr. Virani said in an interview. He also predicted that use of both classes in these patients, including combination treatment, will likely soon expand.
 

‘A lot of interest’ in combining an SGLT2 inhibitor and a GLP-1 RA

“There will be a lot of interest in combing the two classes. It makes intuitive sense [to treat with both classes] because most patients with diabetes need more than one drug” for glycemic control, he noted. “Why not use two classes that each reduce a patient’s risk” for adverse outcomes involving ASCVD, heart failure, and renal dysfunction, added Dr. Virani.

The study run by Dr. Lopez and his associates used data collected in the National VA Database and included 121,156 patients with both type 2 diabetes and established ASCVD. Using propensity-score matching the researchers compiled three subgroups that each included 5,277 matched patients. One subgroup had patients prescribed an SGLT2 inhibitor, a second subgroup included patients on a GLP-1 RA, and a third subgroup had patients on agents from both classes. Patient matching relied on age, sex, left ventricular ejection fraction, hemoglobin A1c level, systolic blood pressure, and the presence of coronary artery disease or peripheral artery disease.

Patients included in the analysis averaged about 67 years of age; 97% were men, their average body mass index was about 34 kg/m², their average A1c was about 7.9%, their average estimated glomerular filtration rate was about 55-66 mL/min per 1.73 m², and their average left ventricular ejection fraction was about 55%. The database provided a median follow-up of 902 days (about 2.5 years). The prespecified primary endpoint focused on events that occurred during the first year of follow-up, but the investigators also ran a 3-year follow-up analysis on a post hoc basis.

The most common SGLT2 inhibitor received by these patients was empagliflozin (Jardiance), used on virtually everyone who received an agent from this class. In contrast, the GLP-1 RA drugs that patients received split more widely. The most prescribed agent was liraglutide (Victoza), followed by semaglutide (Ozempic), and dulaglutide (Trulicity), with fewer than 5% receiving exenatide (Bydureon, Byetta).

Regarding other treatments, about 97% of all patients received a statin, about 94% were on a renin-angiotensin system inhibitor, about 90% were on metformin, and roughly 75% were on insulin, aspirin, and a beta-blocker, with smaller numbers on other types of agents.

For the study’s primary endpoint, the 1-year incidence of combined ASCVD events including all-cause death, patients on agents from both classes had a significant 46% reduced rate compared with those on an SGLT2 inhibitor only, and a significant 49% reduced rate, compared with those on a GLP-1 RA only. These between-group separations broadened slightly during 3-year follow-up. Dr. Lopez did not report results of a direct comparison between patients on just an SGLT2 inhibitor and those on just a GLP-1 RA.

For the endpoint of all-cause death, those on combined treatment had a 1-year rate that was 83% below the rate among patients on only an SGLT2 inhibitor, and 81% below the rate among patients who received a GLP-1 RA but not the other class.

Dr. Lopez cautioned that selection bias could have influenced the outcomes of patients who received both classes rather than one or the other, and he also highlighted that the analysis relied on administrative data rather than information gleaned from more detailed medical records or prospectively collected findings and was limited by only including a very small number of women.

“Our results need to be validated in prospective studies,” he declared.

Dr. Lopez and Dr. Virani had no commercial disclosures.

At least one in four adults worldwide is thought to have nonalcoholic fatty liver disease, a major risk factor for cardiovascular disease (CVD), which is the leading cause of death in NAFLD, but the condition is widely underdiagnosed, according to a new American Heart Association scientific statement on NAFLD and cardiovascular risks.

The statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, aims to increase awareness of NAFLD among cardiologists and other clinicians treating vulnerable patients. It pulls together the existing evidence for using imaging to diagnose NAFLD as well as the role of current and emerging treatments for managing the disease.

“NAFLD is common, but most patients are undiagnosed,” statement writing committee chair P. Barton Duell, MD, said in an interview. “The identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD. Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition.”

Dr. Duell is a professor at the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University, Portland.

This is the AHA’s first scientific statement on NAFLD. In 2021, the association issued a statement on obesity and CVD). Also in 2021, a multiorganization group headed by the American Gastroenterological Association published a “Call to Action” on nonalcoholic steatohepatitis (NASH) , a form of NAFLD that’s characterized by inflammation and scarring of the liver, and typically requires a liver biopsy for diagnosis.

Key take-homes

The AHA statement on NAFLD is sweeping. Among its key take-home messages:

• Calling into question the effectiveness of AST and ALT testing for diagnosing NAFLD and NASH.
• Providing context to the role of insulin resistance – either with or without diabetes – as well as obesity (particularly visceral adiposity), metabolic syndrome, and dyslipidemia in NAFLD.
• Advocating for lifestyle interventions – diet, exercise, weight loss and alcohol avoidance – as the key therapeutic intervention for NAFLD.
• Asserting that glucagonlike peptide–1 receptor agonists may modestly improve NAFLD.

The statement also tackles the differences in terminology different organizations use to describe NAFLD. “The terminology section is important to ensure everyone is using the right terminology in assessing patients, as well as choosing appropriate treatment interventions,” Dr. Duell said.

The statement also explores genetic factors that can predispose people to NAFLD, Dr. Duell pointed out, and it goes into detail about strategies for screening NAFLD and NASH. “It is not possible to diagnose NAFLD without understanding the pros and cons of various screening modalities, as well as the lack of sensitivity of some tests for detection of NAFLD We hope this information will increase success in screening for and early identification of NAFLD.”

Dr. Duell explained the rationale for issuing the statement. “Rates of NAFLD are increasing worldwide in association with rising rates of elevated body mass index and the metabolic syndrome, but the condition is commonly undiagnosed,” he said. “This allows patients to experience progression of disease, leading to hepatic and cardiovascular complications.” 

Avoiding NAFLD risk factors along with early diagnosis and treatment “may have the potential to mitigate long-term complications from NAFLD,” Dr. Duell said.

“This is one of first times where we really look at cardiovascular risks associated with NAFLD and pinpoint the risk factors, the imaging tools that can be used for diagnosing fatty liver disease, and ultimately what potential treatments we can consider,” Tiffany M. Powell-Wiley, MD, MPH, author of the AHA statement on obesity and CV risk, said in an interview.

“NAFLD has not been at the forefront of  cardiologists’ minds, but this statement highlights the importance of liver fat as a fat depot,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory at the National Heart, Lung, and Blood Institute in Bethesda, Md.

“It does provide greater clarity for us as cardiologists, especially when thinking about what is required for diagnosis and ultimately how this relates to cardiovascular disease for people with fatty liver disease,” she said.

Dr. Duell and Dr. Powell-Wiley have no relevant relationships to disclose.


 

At least one in four adults worldwide is thought to have nonalcoholic fatty liver disease, a major risk factor for cardiovascular disease (CVD), which is the leading cause of death in NAFLD, but the condition is widely underdiagnosed, according to a new American Heart Association scientific statement on NAFLD and cardiovascular risks.

The statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, aims to increase awareness of NAFLD among cardiologists and other clinicians treating vulnerable patients. It pulls together the existing evidence for using imaging to diagnose NAFLD as well as the role of current and emerging treatments for managing the disease.

“NAFLD is common, but most patients are undiagnosed,” statement writing committee chair P. Barton Duell, MD, said in an interview. “The identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD. Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition.”

Dr. Duell is a professor at the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University, Portland.

This is the AHA’s first scientific statement on NAFLD. In 2021, the association issued a statement on obesity and CVD). Also in 2021, a multiorganization group headed by the American Gastroenterological Association published a “Call to Action” on nonalcoholic steatohepatitis (NASH) , a form of NAFLD that’s characterized by inflammation and scarring of the liver, and typically requires a liver biopsy for diagnosis.

Key take-homes

The AHA statement on NAFLD is sweeping. Among its key take-home messages:

• Calling into question the effectiveness of AST and ALT testing for diagnosing NAFLD and NASH.
• Providing context to the role of insulin resistance – either with or without diabetes – as well as obesity (particularly visceral adiposity), metabolic syndrome, and dyslipidemia in NAFLD.
• Advocating for lifestyle interventions – diet, exercise, weight loss and alcohol avoidance – as the key therapeutic intervention for NAFLD.
• Asserting that glucagonlike peptide–1 receptor agonists may modestly improve NAFLD.

The statement also tackles the differences in terminology different organizations use to describe NAFLD. “The terminology section is important to ensure everyone is using the right terminology in assessing patients, as well as choosing appropriate treatment interventions,” Dr. Duell said.

The statement also explores genetic factors that can predispose people to NAFLD, Dr. Duell pointed out, and it goes into detail about strategies for screening NAFLD and NASH. “It is not possible to diagnose NAFLD without understanding the pros and cons of various screening modalities, as well as the lack of sensitivity of some tests for detection of NAFLD We hope this information will increase success in screening for and early identification of NAFLD.”

Dr. Duell explained the rationale for issuing the statement. “Rates of NAFLD are increasing worldwide in association with rising rates of elevated body mass index and the metabolic syndrome, but the condition is commonly undiagnosed,” he said. “This allows patients to experience progression of disease, leading to hepatic and cardiovascular complications.” 

Avoiding NAFLD risk factors along with early diagnosis and treatment “may have the potential to mitigate long-term complications from NAFLD,” Dr. Duell said.

“This is one of first times where we really look at cardiovascular risks associated with NAFLD and pinpoint the risk factors, the imaging tools that can be used for diagnosing fatty liver disease, and ultimately what potential treatments we can consider,” Tiffany M. Powell-Wiley, MD, MPH, author of the AHA statement on obesity and CV risk, said in an interview.

“NAFLD has not been at the forefront of  cardiologists’ minds, but this statement highlights the importance of liver fat as a fat depot,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory at the National Heart, Lung, and Blood Institute in Bethesda, Md.

“It does provide greater clarity for us as cardiologists, especially when thinking about what is required for diagnosis and ultimately how this relates to cardiovascular disease for people with fatty liver disease,” she said.

Dr. Duell and Dr. Powell-Wiley have no relevant relationships to disclose.


 

At least one in four adults worldwide is thought to have nonalcoholic fatty liver disease, a major risk factor for cardiovascular disease (CVD), which is the leading cause of death in NAFLD, but the condition is widely underdiagnosed, according to a new American Heart Association scientific statement on NAFLD and cardiovascular risks.

The statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, aims to increase awareness of NAFLD among cardiologists and other clinicians treating vulnerable patients. It pulls together the existing evidence for using imaging to diagnose NAFLD as well as the role of current and emerging treatments for managing the disease.

“NAFLD is common, but most patients are undiagnosed,” statement writing committee chair P. Barton Duell, MD, said in an interview. “The identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD. Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition.”

Dr. Duell is a professor at the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University, Portland.

This is the AHA’s first scientific statement on NAFLD. In 2021, the association issued a statement on obesity and CVD). Also in 2021, a multiorganization group headed by the American Gastroenterological Association published a “Call to Action” on nonalcoholic steatohepatitis (NASH) , a form of NAFLD that’s characterized by inflammation and scarring of the liver, and typically requires a liver biopsy for diagnosis.

Key take-homes

The AHA statement on NAFLD is sweeping. Among its key take-home messages:

• Calling into question the effectiveness of AST and ALT testing for diagnosing NAFLD and NASH.
• Providing context to the role of insulin resistance – either with or without diabetes – as well as obesity (particularly visceral adiposity), metabolic syndrome, and dyslipidemia in NAFLD.
• Advocating for lifestyle interventions – diet, exercise, weight loss and alcohol avoidance – as the key therapeutic intervention for NAFLD.
• Asserting that glucagonlike peptide–1 receptor agonists may modestly improve NAFLD.

The statement also tackles the differences in terminology different organizations use to describe NAFLD. “The terminology section is important to ensure everyone is using the right terminology in assessing patients, as well as choosing appropriate treatment interventions,” Dr. Duell said.

The statement also explores genetic factors that can predispose people to NAFLD, Dr. Duell pointed out, and it goes into detail about strategies for screening NAFLD and NASH. “It is not possible to diagnose NAFLD without understanding the pros and cons of various screening modalities, as well as the lack of sensitivity of some tests for detection of NAFLD We hope this information will increase success in screening for and early identification of NAFLD.”

Dr. Duell explained the rationale for issuing the statement. “Rates of NAFLD are increasing worldwide in association with rising rates of elevated body mass index and the metabolic syndrome, but the condition is commonly undiagnosed,” he said. “This allows patients to experience progression of disease, leading to hepatic and cardiovascular complications.” 

Avoiding NAFLD risk factors along with early diagnosis and treatment “may have the potential to mitigate long-term complications from NAFLD,” Dr. Duell said.

“This is one of first times where we really look at cardiovascular risks associated with NAFLD and pinpoint the risk factors, the imaging tools that can be used for diagnosing fatty liver disease, and ultimately what potential treatments we can consider,” Tiffany M. Powell-Wiley, MD, MPH, author of the AHA statement on obesity and CV risk, said in an interview.

“NAFLD has not been at the forefront of  cardiologists’ minds, but this statement highlights the importance of liver fat as a fat depot,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory at the National Heart, Lung, and Blood Institute in Bethesda, Md.

“It does provide greater clarity for us as cardiologists, especially when thinking about what is required for diagnosis and ultimately how this relates to cardiovascular disease for people with fatty liver disease,” she said.

Dr. Duell and Dr. Powell-Wiley have no relevant relationships to disclose.


 

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

WASHINGTON – Treatment of patients acutely hospitalized for heart failure with the SGLT2 inhibitor empagliflozin led to a rapid incremental increase in patient well-being, compared with control patients who received placebo, that appeared after 2 weeks on treatment in a secondary analysis from 530 randomized patients in the EMPULSE trial.

To Mikhail N. Kosiborod, MD, a coinvestigator for EMPULSE who presented new analysis at the annual scientific sessions of the American College of Cardiology, the message from the quick response of acutely hospitalized patients to empagliflozin was clear: “Use these medications, SGLT2 [sodium-glucose cotransporter 2] inhibitors, as early as possible. We’ve seen with other medications that if they are not prescribed during hospitalization it’s unlikely to happen post discharge,” said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

Mitchel L. Zoler/MDedge News

“To our knowledge, the very early improvement in the Kansas City Cardiomyopathy Questionnaire [KCCQ] score – a well-known predictor of cardiovascular death and heart failure readmissions – that we observed with empagliflozin at 15 days is the first such observation, and if corroborated by future studies would suggest that initiation of SGLT2 inhibitors during hospitalization for acute heart failure may be a tool for improving the quality of hospital-to-home transitions,” wrote Dr. Kosiborod and his associates in the published version of their report that appeared concurrently with his report at the meeting.

“These data really support initiation [of empagliflozin or another SGLT2 inhibitor] in hospital, presuming that the patient has no contraindications,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and designated discussant for the report.

“The fact that the benefit kicks in so early is really important, because there is a bit of a penalty to wait” to start treatment with an agent from the SGLT2-inhibitor class, added Dr. Bhatt, who is also executive director of interventional cardiovascular programs at Brigham and Women’s Health, in Boston.

In hospital creates a teachable moment

Starting treatment when a patient is hospitalized is also important as “a teachable moment,” added Dr. Bhatt in an interview. “A physician can say to a patient ‘take this drug, and it will prevent you from returning to the hospital,’ at a time when it’s more likely to be impactful, compared with when a patient is out of the hospital and feeling okay and adherence will likely be much lower.”

Mitchel L. Zoler/MDedge News

The results Dr. Kosiborod reported on quality-of-life parameters measured with the KCCQ expanded on what he and his coinvestigators first reported in 2021 with the primary results from EMPULSE, which enrolled 530 patients at 118 centers in 15 countries during June 2020–February 2021. The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission. Enrolled patients averaged about 71 years of age, about two-thirds were men, 45% had diabetes, 32% had left ventricular ejection fraction greater than 40%, and about two-thirds had decompensated chronic heart failure, while a third had acute de novo heart failure.

The primary outcome for EMPULSE was a combined endpoint of “total clinical endpoints” that included all-cause mortality, heart failure events (heart failure hospitalizations, urgent heart failure visits, and unplanned outpatient heart failure visits) or at least a 5-point change from baseline in the KCCQ score. Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74).
 

Benefit independent of baseline symptomatic impairment

Among the new secondary analyses that Dr. Kosiborod reported was a post-hoc calculation that divided the study cohort into tertiles of baseline KCCQ score. The results showed that the degree of improvement for the primary, 90-day outcome of “total clinical benefit” compared with placebo was consistent across all three KCCQ-score tertiles, showing that empagliflozin’s benefit was “independent of symptomatic impairment at baseline,” he said.

The degree of improvement was also similar across all the tested domains of the KCCQ, including the overall summary, clinical summary, the physical limitations, and quality-of-life scores. Average improvement in KCCQ total symptom score 15 days after treatment onset was 5.35 points, compared with control patients. On an individual-patient basis, a change in KCCQ score of 5 points or more was previously shown to represent a clinically meaningful change.

“Treatment of patients with heart failure is geared to making patients live longer and stay out of the hospital. Enabling patients to feel better is an equally important goal of management, but not all treatments for heart failure can do that. These data from EMPULSE show that, in addition to other clinical benefits, patients also feel better on an SGLT2 inhibitor after just 2 weeks,” Dr. Kosiborod said in an interview.

EMPULSE builds on SOLOIST-WHF

EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHF pivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment.

“It’s reassuring to see two different drugs and research groups get essentially the same result, showing that starting an SGLT2 inhibitor is safe and effective in selected patients with no contraindications,” said Dr. Bhatt, who was lead investigator for SOLOIST-WHF.

The accumulating evidence for the safety and value of starting an SGLT2 inhibitor when patients are hospitalized for acute heart failure is making this approach increasingly routine for patients who present with heart failure with reduced ejection fraction at Saint Luke’s-Mid America Heart Institute, said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri, Kansas City.

“I think we’ll also gradually start using [an SGLT2 inhibitor] in patients hospitalized with heart failure with preserved ejection fraction [HFpEF],” he added, based on the findings from SOLOIST-WHF and EMPULSE, and also recent evidence showing safety and efficacy of empagliflozin in patients with chronic HFpEF in the EMPEROR-Preserved trial, and for dapagliflozin (Farxiga) in the PRESERVED-HF trial.

Empagliflozin recently received from the U.S. Food and Drug Administration an expanded label indication for treating patients with heart failure with no specification for a level of left ventricular ejection fraction. An outcome trial of dapagliflozin in more than 6,000 patients with HFpEF, DELIVER, is currently ongoing but is expected to report results soon.

“The evidence is already compelling that the benefits outweigh the risk. Results from both SOLOIST-WHF and EMPULSE show that there are no significant safety concerns” when these agents are used in patients with acute heart failure,” Dr. Kosiborod declared.

EMPULSE was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). SOLOIST-WHF was sponsored by Sanofi and Lexicon, the companies that have been developing sotagliflozin. Dr. Kosiborod has been a consultant to and received research funding from Boehringer Ingelheim and Eli Lilly, and he has been a consultant or adviser to or led trials on behalf of numerous other companies. Dr. Bhatt has been an adviser to Boehringer Ingelheim and numerous other companies, and he has received research funding from Sanofi, Lexicon, Boehringer Ingelheim, Eli Lilly, and numerous other companies.

Between 2014 and 2020, the frequency of adverse pregnancy outcomes in the United States increased among women with gestational diabetes, with persisting differences in adverse outcomes by race and ethnicity, according to a report in JAMA

“[Previous] population-based studies on racial and ethnic disparities in gestational diabetes have focused on differences in the rate of diagnosis, rather than adverse pregnancy outcomes,” lead author Kartik K. Venkatesh, MD, PhD, of Ohio State University, Columbus, and colleagues explained.

The researchers conducted a cross-sectional, descriptive study to evaluate whether the frequency of adverse pregnancy outcomes with gestational diabetes changed over time and whether the risk of these outcomes differed by maternal race and ethnicity.

The data were obtained from the Centers for Disease Control and Prevention’s National Center for Health Statistics Natality Files. Exposures of interest were year of delivery, as well as race and ethnicity.
 

Results

The study cohort included 1,560,822 pregnant women with gestational diabetes aged 15-44 years. Among the study participants the mean age was 31 years (standard deviation, 5.5 years) and the majority were White (48%), followed by Hispanic/Latina (27%), Asian/Pacific Islander (13%), and Black (12%).

There was a significant increase in the overall frequency of transfusion (8.0%; 95% confidence interval, 3.8%-12.4%), preeclampsia or gestational hypertension (4.2%; 95% CI, 3.3%-5.2%), NICU admission (1.0%; 95% CI, 0.3%-1.7%), and preterm birth at less than 37 weeks (0.9%; 95% CI, 0.3%-1.5%) from 2014 to 2020 for these women and their infants.

In addition, there was a significant decrease in the following outcomes: macrosomia (–4.7%; 95% CI, –5.3% to –4.0%), cesarean delivery (–1.4%; 95% CI, –1.7% to –1.1%), primary cesarean delivery (–1.2%; 95% CI, –1.5% to –0.9%), and large for gestational age (–2.3%; 95% CI, –2.8% to –1.8%), but there was no significant differences in maternal ICU admission and small-for-gestational-age infants.

From 2014 through 2020, differences in adverse outcomes by race and ethnicity persisted; in comparison with Whites, Black participants were at significantly higher risk of all evaluated outcomes, except for macrosomia and large for gestational age.

Hispanic/Latina and Asian/Pacific Islander individuals were also at significantly higher risk of preterm birth, NICU admission, maternal ICU admission, and small for gestational age. Furthermore, American Indian participants were at significantly higher risk of all evaluated outcomes, except for cesarean delivery and small for gestational age.
 

Results in context

Health policy researcher Felicia Hill-Briggs, PhD, at the Feinstein Institutes for Medical Research in Manhasset, N.Y. commented: “Two alarming trends highlighted by this study: 1) Racial and ethnic inequities in adverse gestational diabetes outcomes; and 2) the rising rates of gestational diabetes overall – both must and can be halted.”

“Optimizing medical management of gestational diabetes, whether through improved access to diabetes care in pregnancy, behavioral interventions, and pharmacotherapy can decrease the risk of adverse pregnancy outcomes,” Dr. Venkatesh commented. “It is possible that the equitable delivery of these interventions to address glycemic control could decrease racial and ethnic disparities in adverse pregnancy outcomes among individuals with gestational diabetes.”

Dr. Venkatesh and his colleagues acknowledged that a key limitation of the study was the use of administrative data; thus, inferences on maternal care improvements could not be determined.

“Further research could focus on greater understanding of racial and ethnic differences in the management of gestational diabetes,” the researchers concluded.

This study was supported by the Care Innovation and Community Improvement Program at Ohio State University. One author reported receiving grants from the National Institutes of Health outside of this study. The other authors reported no relevant disclosures. Dr. Hill-Briggs had no relevant disclosures.

Between 2014 and 2020, the frequency of adverse pregnancy outcomes in the United States increased among women with gestational diabetes, with persisting differences in adverse outcomes by race and ethnicity, according to a report in JAMA

“[Previous] population-based studies on racial and ethnic disparities in gestational diabetes have focused on differences in the rate of diagnosis, rather than adverse pregnancy outcomes,” lead author Kartik K. Venkatesh, MD, PhD, of Ohio State University, Columbus, and colleagues explained.

The researchers conducted a cross-sectional, descriptive study to evaluate whether the frequency of adverse pregnancy outcomes with gestational diabetes changed over time and whether the risk of these outcomes differed by maternal race and ethnicity.

The data were obtained from the Centers for Disease Control and Prevention’s National Center for Health Statistics Natality Files. Exposures of interest were year of delivery, as well as race and ethnicity.
 

Results

The study cohort included 1,560,822 pregnant women with gestational diabetes aged 15-44 years. Among the study participants the mean age was 31 years (standard deviation, 5.5 years) and the majority were White (48%), followed by Hispanic/Latina (27%), Asian/Pacific Islander (13%), and Black (12%).

There was a significant increase in the overall frequency of transfusion (8.0%; 95% confidence interval, 3.8%-12.4%), preeclampsia or gestational hypertension (4.2%; 95% CI, 3.3%-5.2%), NICU admission (1.0%; 95% CI, 0.3%-1.7%), and preterm birth at less than 37 weeks (0.9%; 95% CI, 0.3%-1.5%) from 2014 to 2020 for these women and their infants.

In addition, there was a significant decrease in the following outcomes: macrosomia (–4.7%; 95% CI, –5.3% to –4.0%), cesarean delivery (–1.4%; 95% CI, –1.7% to –1.1%), primary cesarean delivery (–1.2%; 95% CI, –1.5% to –0.9%), and large for gestational age (–2.3%; 95% CI, –2.8% to –1.8%), but there was no significant differences in maternal ICU admission and small-for-gestational-age infants.

From 2014 through 2020, differences in adverse outcomes by race and ethnicity persisted; in comparison with Whites, Black participants were at significantly higher risk of all evaluated outcomes, except for macrosomia and large for gestational age.

Hispanic/Latina and Asian/Pacific Islander individuals were also at significantly higher risk of preterm birth, NICU admission, maternal ICU admission, and small for gestational age. Furthermore, American Indian participants were at significantly higher risk of all evaluated outcomes, except for cesarean delivery and small for gestational age.
 

Results in context

Health policy researcher Felicia Hill-Briggs, PhD, at the Feinstein Institutes for Medical Research in Manhasset, N.Y. commented: “Two alarming trends highlighted by this study: 1) Racial and ethnic inequities in adverse gestational diabetes outcomes; and 2) the rising rates of gestational diabetes overall – both must and can be halted.”

“Optimizing medical management of gestational diabetes, whether through improved access to diabetes care in pregnancy, behavioral interventions, and pharmacotherapy can decrease the risk of adverse pregnancy outcomes,” Dr. Venkatesh commented. “It is possible that the equitable delivery of these interventions to address glycemic control could decrease racial and ethnic disparities in adverse pregnancy outcomes among individuals with gestational diabetes.”

Dr. Venkatesh and his colleagues acknowledged that a key limitation of the study was the use of administrative data; thus, inferences on maternal care improvements could not be determined.

“Further research could focus on greater understanding of racial and ethnic differences in the management of gestational diabetes,” the researchers concluded.

This study was supported by the Care Innovation and Community Improvement Program at Ohio State University. One author reported receiving grants from the National Institutes of Health outside of this study. The other authors reported no relevant disclosures. Dr. Hill-Briggs had no relevant disclosures.

Between 2014 and 2020, the frequency of adverse pregnancy outcomes in the United States increased among women with gestational diabetes, with persisting differences in adverse outcomes by race and ethnicity, according to a report in JAMA

“[Previous] population-based studies on racial and ethnic disparities in gestational diabetes have focused on differences in the rate of diagnosis, rather than adverse pregnancy outcomes,” lead author Kartik K. Venkatesh, MD, PhD, of Ohio State University, Columbus, and colleagues explained.

The researchers conducted a cross-sectional, descriptive study to evaluate whether the frequency of adverse pregnancy outcomes with gestational diabetes changed over time and whether the risk of these outcomes differed by maternal race and ethnicity.

The data were obtained from the Centers for Disease Control and Prevention’s National Center for Health Statistics Natality Files. Exposures of interest were year of delivery, as well as race and ethnicity.
 

Results

The study cohort included 1,560,822 pregnant women with gestational diabetes aged 15-44 years. Among the study participants the mean age was 31 years (standard deviation, 5.5 years) and the majority were White (48%), followed by Hispanic/Latina (27%), Asian/Pacific Islander (13%), and Black (12%).

There was a significant increase in the overall frequency of transfusion (8.0%; 95% confidence interval, 3.8%-12.4%), preeclampsia or gestational hypertension (4.2%; 95% CI, 3.3%-5.2%), NICU admission (1.0%; 95% CI, 0.3%-1.7%), and preterm birth at less than 37 weeks (0.9%; 95% CI, 0.3%-1.5%) from 2014 to 2020 for these women and their infants.

In addition, there was a significant decrease in the following outcomes: macrosomia (–4.7%; 95% CI, –5.3% to –4.0%), cesarean delivery (–1.4%; 95% CI, –1.7% to –1.1%), primary cesarean delivery (–1.2%; 95% CI, –1.5% to –0.9%), and large for gestational age (–2.3%; 95% CI, –2.8% to –1.8%), but there was no significant differences in maternal ICU admission and small-for-gestational-age infants.

From 2014 through 2020, differences in adverse outcomes by race and ethnicity persisted; in comparison with Whites, Black participants were at significantly higher risk of all evaluated outcomes, except for macrosomia and large for gestational age.

Hispanic/Latina and Asian/Pacific Islander individuals were also at significantly higher risk of preterm birth, NICU admission, maternal ICU admission, and small for gestational age. Furthermore, American Indian participants were at significantly higher risk of all evaluated outcomes, except for cesarean delivery and small for gestational age.
 

Results in context

Health policy researcher Felicia Hill-Briggs, PhD, at the Feinstein Institutes for Medical Research in Manhasset, N.Y. commented: “Two alarming trends highlighted by this study: 1) Racial and ethnic inequities in adverse gestational diabetes outcomes; and 2) the rising rates of gestational diabetes overall – both must and can be halted.”

“Optimizing medical management of gestational diabetes, whether through improved access to diabetes care in pregnancy, behavioral interventions, and pharmacotherapy can decrease the risk of adverse pregnancy outcomes,” Dr. Venkatesh commented. “It is possible that the equitable delivery of these interventions to address glycemic control could decrease racial and ethnic disparities in adverse pregnancy outcomes among individuals with gestational diabetes.”

Dr. Venkatesh and his colleagues acknowledged that a key limitation of the study was the use of administrative data; thus, inferences on maternal care improvements could not be determined.

“Further research could focus on greater understanding of racial and ethnic differences in the management of gestational diabetes,” the researchers concluded.

This study was supported by the Care Innovation and Community Improvement Program at Ohio State University. One author reported receiving grants from the National Institutes of Health outside of this study. The other authors reported no relevant disclosures. Dr. Hill-Briggs had no relevant disclosures.

Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.

“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.

“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.

The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.

However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
 

Is there any way to reduce exposure?

PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.

Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.

The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.

While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”

“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.

In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
 

Prospective findings from the SWAN-MPS study

The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.

Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.

Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.

namiroz/iStock/Getty Images

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

Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.

“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.

“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.

The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.

However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
 

Is there any way to reduce exposure?

PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.

Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.

The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.

While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”

“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.

In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
 

Prospective findings from the SWAN-MPS study

The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.

Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.

Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.

namiroz/iStock/Getty Images

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

Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.

“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.

“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.

The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.

However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
 

Is there any way to reduce exposure?

PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.

Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.

The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.

While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”

“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.

In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
 

Prospective findings from the SWAN-MPS study

The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.

Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.

Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.

namiroz/iStock/Getty Images

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