Diabetes

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The widely used antidiabetic drug metformin may cause genital birth defects such as undescended testicles and urethral problems in the male offspring of men who take the medication, researchers have found.

The association appears to involve the effects of metformin on the development of sperm during a critical window prior to conception. Female offspring were not affected. Although previous studies have linked diabetes with fertility problems in men, the latest study is the first to show that these problems can result from treatment rather than the disease itself, according to the researchers, whose findings appear in Annals of Internal Medicine.

“This is the first data to suggest that paternal metformin [use] may be associated with birth defects in children. As such, it would be early to begin to alter clinical practice,” Michael Eisenberg, MD, director of male reproductive medicine and surgery, department of urology, Stanford (Calif.) University, who is a coauthor of the study, said in an interview. “However, if it is confirmed in other populations, then it may begin to enter counseling discussions.”

Dr. Eisenberg added that eating a nutritious diet, exercising, and maintaining a healthy body weight “can improve a man’s health and likely his fertility as well.”

For the new study, Dr. Eisenberg and colleagues analyzed records in a registry of all 1.25 million births that occurred in Denmark between 1997 and 2016. The registry included information on birth defects and parental drug prescriptions.

Offspring were considered exposed to a diabetes drug if a father had filled one or more prescriptions for the medications during the 3 months prior to conception, when the fertilizing sperm would have been produced.

The final analysis included 1,116,779 offspring – all singleton births to women without a history of diabetes or essential hypertension – of whom 7,029 were exposed to diabetes drugs via the father, and 3.3% (n = 36,585) had one or more major birth defects.

Among male offspring whose fathers had taken metformin (n = 1,451), there was a 3.4-fold greater incidence of major genitourinary birth defects, according to the researchers. The study failed to find associations between birth defects and the use of insulin. Although a signal did emerge for sulfonylurea-based drugs, it did not reach statistical significance.

The risk associated with metformin did not appear for men who were prescribed the drug in the year before or after sperm development. Nor was it evident in siblings of the boys with birth defects who were not considered to have been exposed to the medication, the researchers reported.

In an editorial accompanying the journal article, Germaine Buck Louis, PhD, a reproductive and perinatal epidemiologist, wrote: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”

Dr. Louis, dean of the College of Health and Human Services at George Mason University, Washington, said a key limitation of the research is the lack of data on how well men in the study adhered to their diabetes treatment. Nevertheless, “clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

The researchers received funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

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

The widely used antidiabetic drug metformin may cause genital birth defects such as undescended testicles and urethral problems in the male offspring of men who take the medication, researchers have found.

The association appears to involve the effects of metformin on the development of sperm during a critical window prior to conception. Female offspring were not affected. Although previous studies have linked diabetes with fertility problems in men, the latest study is the first to show that these problems can result from treatment rather than the disease itself, according to the researchers, whose findings appear in Annals of Internal Medicine.

“This is the first data to suggest that paternal metformin [use] may be associated with birth defects in children. As such, it would be early to begin to alter clinical practice,” Michael Eisenberg, MD, director of male reproductive medicine and surgery, department of urology, Stanford (Calif.) University, who is a coauthor of the study, said in an interview. “However, if it is confirmed in other populations, then it may begin to enter counseling discussions.”

Dr. Eisenberg added that eating a nutritious diet, exercising, and maintaining a healthy body weight “can improve a man’s health and likely his fertility as well.”

For the new study, Dr. Eisenberg and colleagues analyzed records in a registry of all 1.25 million births that occurred in Denmark between 1997 and 2016. The registry included information on birth defects and parental drug prescriptions.

Offspring were considered exposed to a diabetes drug if a father had filled one or more prescriptions for the medications during the 3 months prior to conception, when the fertilizing sperm would have been produced.

The final analysis included 1,116,779 offspring – all singleton births to women without a history of diabetes or essential hypertension – of whom 7,029 were exposed to diabetes drugs via the father, and 3.3% (n = 36,585) had one or more major birth defects.

Among male offspring whose fathers had taken metformin (n = 1,451), there was a 3.4-fold greater incidence of major genitourinary birth defects, according to the researchers. The study failed to find associations between birth defects and the use of insulin. Although a signal did emerge for sulfonylurea-based drugs, it did not reach statistical significance.

The risk associated with metformin did not appear for men who were prescribed the drug in the year before or after sperm development. Nor was it evident in siblings of the boys with birth defects who were not considered to have been exposed to the medication, the researchers reported.

In an editorial accompanying the journal article, Germaine Buck Louis, PhD, a reproductive and perinatal epidemiologist, wrote: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”

Dr. Louis, dean of the College of Health and Human Services at George Mason University, Washington, said a key limitation of the research is the lack of data on how well men in the study adhered to their diabetes treatment. Nevertheless, “clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

The researchers received funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

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

The widely used antidiabetic drug metformin may cause genital birth defects such as undescended testicles and urethral problems in the male offspring of men who take the medication, researchers have found.

The association appears to involve the effects of metformin on the development of sperm during a critical window prior to conception. Female offspring were not affected. Although previous studies have linked diabetes with fertility problems in men, the latest study is the first to show that these problems can result from treatment rather than the disease itself, according to the researchers, whose findings appear in Annals of Internal Medicine.

“This is the first data to suggest that paternal metformin [use] may be associated with birth defects in children. As such, it would be early to begin to alter clinical practice,” Michael Eisenberg, MD, director of male reproductive medicine and surgery, department of urology, Stanford (Calif.) University, who is a coauthor of the study, said in an interview. “However, if it is confirmed in other populations, then it may begin to enter counseling discussions.”

Dr. Eisenberg added that eating a nutritious diet, exercising, and maintaining a healthy body weight “can improve a man’s health and likely his fertility as well.”

For the new study, Dr. Eisenberg and colleagues analyzed records in a registry of all 1.25 million births that occurred in Denmark between 1997 and 2016. The registry included information on birth defects and parental drug prescriptions.

Offspring were considered exposed to a diabetes drug if a father had filled one or more prescriptions for the medications during the 3 months prior to conception, when the fertilizing sperm would have been produced.

The final analysis included 1,116,779 offspring – all singleton births to women without a history of diabetes or essential hypertension – of whom 7,029 were exposed to diabetes drugs via the father, and 3.3% (n = 36,585) had one or more major birth defects.

Among male offspring whose fathers had taken metformin (n = 1,451), there was a 3.4-fold greater incidence of major genitourinary birth defects, according to the researchers. The study failed to find associations between birth defects and the use of insulin. Although a signal did emerge for sulfonylurea-based drugs, it did not reach statistical significance.

The risk associated with metformin did not appear for men who were prescribed the drug in the year before or after sperm development. Nor was it evident in siblings of the boys with birth defects who were not considered to have been exposed to the medication, the researchers reported.

In an editorial accompanying the journal article, Germaine Buck Louis, PhD, a reproductive and perinatal epidemiologist, wrote: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.”

Dr. Louis, dean of the College of Health and Human Services at George Mason University, Washington, said a key limitation of the research is the lack of data on how well men in the study adhered to their diabetes treatment. Nevertheless, “clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.”

The researchers received funding from the National Institutes of Health and the Centers for Disease Control and Prevention.

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

The health benefits of intermittent fasting are slowly being clarified as more evidence continues to emerge, say the authors of a new review of 21 studies. Initial findings suggest that fasting might be effective for mild to moderate weight loss for certain groups of people, at least in the short term.

And data so far at least dispel the myth that “people are going to feel weak and not be able to concentrate during fasting,” lead researcher Krista A. Varady, PhD, professor of nutrition in the University of Illinois at Chicago, noted in a press release from her university.

“We’ve shown it is the opposite,” she said. “They actually have a better ability to concentrate.”

Wildpixel/thinkstockphotos.com

Yet much longer-term data are needed on issues such as safety, Dr. Varady and colleagues note in their review in Nature Reviews: Endocrinology .

The trials so far have only been conducted in adults – generally with overweight or obesity and sometimes hypertension, dyslipidemia, and/or diabetes – but some have been performed in those of normal weight.

Dr. Varady and colleague recommend that those with type 1 diabetes, type 2 diabetes, or other comorbidities, or patients who need to take medications with meals at certain times of the day, should seek clinical supervision when considering intermittent fasting.

And currently, based on existing evidence, intermittent fasting is contraindicated for children under age 12 and those who have a history of an eating disorder or a body mass index <18.5 kg/m². Opinions vary about the safety of supervised fasting in adolescents with obesity. Also, safety has not been evaluated in those older than age 70, and in women who are pregnant or lactating.
 

‘A few studies’ show 3%-8% weight loss over 2-3 months

Despite the recent surge in the popularity of intermittent fasting, “only a few studies have examined the health benefits of these diets in humans,” Dr. Varady and coauthors emphasize.

They identified 21 clinical trials of three types of intermittent fasting strategies:

Alternate day fasting (alternating between consuming 0-500 kcal on “fasting” days, followed by unlimited food on “feasting” days), six trials.

5:2 diet (“feasting” on 5 days and “fasting” on 2 days), seven trials.

Time-restricted eating (eating during a 4- to 8- hour window), nine trials.

The trials were short (mostly 5-12 weeks long) and small (10-150 participants), and mostly conducted in the United States. 

They found these strategies can all produce a mild to moderate 3%-8% weight loss during 8-12 weeks, similar to that attained with a calorie-restricted diet.

Some studies found that patients had improvements in blood pressure, LDL cholesterol, triglycerides, insulin resistance, and hemoglobin A1c.

These weight-loss strategies produced few gastrointestinal, neurological, hormonal, or metabolic adverse effects; “however, as adverse outcomes are not regularly assessed in human trials of fasting, definitive conclusions regarding the safety of these diets are difficult to draw at present,” the researchers caution.

Practical advice, great anecdotes

Typically, 1-2 weeks of adjustment is needed when individuals start intermittent fasting, the researchers say.

While following this eating pattern, patients should be encouraged to consume plenty of fruits, vegetables, and whole grains to boost their fiber and micronutrient intake.

On fasting days, they should consume at least 50 g of lean protein to help control hunger and prevent excessive loss of lean mass. On those days, alcohol is permitted but not recommended. Energy drinks and coffee or tea without sugar, milk, or cream are allowed, and diet soda should be limited to two servings a day because it can increase sugar cravings.

Ideally, clinicians should regularly assess patients for adverse effects during the first 3 months of intermittent fasting. They should also monitor patients for deficiencies in vitamin D, vitamin B₁₂, and electrolytes, as well as for changes in medications for blood pressure, lipids, and glucose that may be needed if patients lose weight.

Patients who reach their weight-loss goals and wish to stop intermittent fasting need to transition to a weight-maintenance program, possibly by increasing energy intake on fasting days to 1,000-1,200 kcal/day or widening the eating window to 12 hours in time-restricted eating.

“I get lots of emails from people saying that they have been on the diet for 10-15 years, and it reversed their type 2 diabetes, and they lost 60 pounds, and it was the only diet they could stick to,” Dr. Varady noted.

“That is always nice to hear, but we really do need long-term data to see if people can do intermittent fasting for the long term,” she reiterated.  

The review was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Varady received author fees from the Hachette Book Group for the book, “The Every Other Day Diet.” The other authors have declared no relevant financial relationships.

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

The health benefits of intermittent fasting are slowly being clarified as more evidence continues to emerge, say the authors of a new review of 21 studies. Initial findings suggest that fasting might be effective for mild to moderate weight loss for certain groups of people, at least in the short term.

And data so far at least dispel the myth that “people are going to feel weak and not be able to concentrate during fasting,” lead researcher Krista A. Varady, PhD, professor of nutrition in the University of Illinois at Chicago, noted in a press release from her university.

“We’ve shown it is the opposite,” she said. “They actually have a better ability to concentrate.”

Wildpixel/thinkstockphotos.com

Yet much longer-term data are needed on issues such as safety, Dr. Varady and colleagues note in their review in Nature Reviews: Endocrinology .

The trials so far have only been conducted in adults – generally with overweight or obesity and sometimes hypertension, dyslipidemia, and/or diabetes – but some have been performed in those of normal weight.

Dr. Varady and colleague recommend that those with type 1 diabetes, type 2 diabetes, or other comorbidities, or patients who need to take medications with meals at certain times of the day, should seek clinical supervision when considering intermittent fasting.

And currently, based on existing evidence, intermittent fasting is contraindicated for children under age 12 and those who have a history of an eating disorder or a body mass index <18.5 kg/m². Opinions vary about the safety of supervised fasting in adolescents with obesity. Also, safety has not been evaluated in those older than age 70, and in women who are pregnant or lactating.
 

‘A few studies’ show 3%-8% weight loss over 2-3 months

Despite the recent surge in the popularity of intermittent fasting, “only a few studies have examined the health benefits of these diets in humans,” Dr. Varady and coauthors emphasize.

They identified 21 clinical trials of three types of intermittent fasting strategies:

Alternate day fasting (alternating between consuming 0-500 kcal on “fasting” days, followed by unlimited food on “feasting” days), six trials.

5:2 diet (“feasting” on 5 days and “fasting” on 2 days), seven trials.

Time-restricted eating (eating during a 4- to 8- hour window), nine trials.

The trials were short (mostly 5-12 weeks long) and small (10-150 participants), and mostly conducted in the United States. 

They found these strategies can all produce a mild to moderate 3%-8% weight loss during 8-12 weeks, similar to that attained with a calorie-restricted diet.

Some studies found that patients had improvements in blood pressure, LDL cholesterol, triglycerides, insulin resistance, and hemoglobin A1c.

These weight-loss strategies produced few gastrointestinal, neurological, hormonal, or metabolic adverse effects; “however, as adverse outcomes are not regularly assessed in human trials of fasting, definitive conclusions regarding the safety of these diets are difficult to draw at present,” the researchers caution.

Practical advice, great anecdotes

Typically, 1-2 weeks of adjustment is needed when individuals start intermittent fasting, the researchers say.

While following this eating pattern, patients should be encouraged to consume plenty of fruits, vegetables, and whole grains to boost their fiber and micronutrient intake.

On fasting days, they should consume at least 50 g of lean protein to help control hunger and prevent excessive loss of lean mass. On those days, alcohol is permitted but not recommended. Energy drinks and coffee or tea without sugar, milk, or cream are allowed, and diet soda should be limited to two servings a day because it can increase sugar cravings.

Ideally, clinicians should regularly assess patients for adverse effects during the first 3 months of intermittent fasting. They should also monitor patients for deficiencies in vitamin D, vitamin B₁₂, and electrolytes, as well as for changes in medications for blood pressure, lipids, and glucose that may be needed if patients lose weight.

Patients who reach their weight-loss goals and wish to stop intermittent fasting need to transition to a weight-maintenance program, possibly by increasing energy intake on fasting days to 1,000-1,200 kcal/day or widening the eating window to 12 hours in time-restricted eating.

“I get lots of emails from people saying that they have been on the diet for 10-15 years, and it reversed their type 2 diabetes, and they lost 60 pounds, and it was the only diet they could stick to,” Dr. Varady noted.

“That is always nice to hear, but we really do need long-term data to see if people can do intermittent fasting for the long term,” she reiterated.  

The review was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Varady received author fees from the Hachette Book Group for the book, “The Every Other Day Diet.” The other authors have declared no relevant financial relationships.

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

The health benefits of intermittent fasting are slowly being clarified as more evidence continues to emerge, say the authors of a new review of 21 studies. Initial findings suggest that fasting might be effective for mild to moderate weight loss for certain groups of people, at least in the short term.

And data so far at least dispel the myth that “people are going to feel weak and not be able to concentrate during fasting,” lead researcher Krista A. Varady, PhD, professor of nutrition in the University of Illinois at Chicago, noted in a press release from her university.

“We’ve shown it is the opposite,” she said. “They actually have a better ability to concentrate.”

Wildpixel/thinkstockphotos.com

Yet much longer-term data are needed on issues such as safety, Dr. Varady and colleagues note in their review in Nature Reviews: Endocrinology .

The trials so far have only been conducted in adults – generally with overweight or obesity and sometimes hypertension, dyslipidemia, and/or diabetes – but some have been performed in those of normal weight.

Dr. Varady and colleague recommend that those with type 1 diabetes, type 2 diabetes, or other comorbidities, or patients who need to take medications with meals at certain times of the day, should seek clinical supervision when considering intermittent fasting.

And currently, based on existing evidence, intermittent fasting is contraindicated for children under age 12 and those who have a history of an eating disorder or a body mass index <18.5 kg/m². Opinions vary about the safety of supervised fasting in adolescents with obesity. Also, safety has not been evaluated in those older than age 70, and in women who are pregnant or lactating.
 

‘A few studies’ show 3%-8% weight loss over 2-3 months

Despite the recent surge in the popularity of intermittent fasting, “only a few studies have examined the health benefits of these diets in humans,” Dr. Varady and coauthors emphasize.

They identified 21 clinical trials of three types of intermittent fasting strategies:

Alternate day fasting (alternating between consuming 0-500 kcal on “fasting” days, followed by unlimited food on “feasting” days), six trials.

5:2 diet (“feasting” on 5 days and “fasting” on 2 days), seven trials.

Time-restricted eating (eating during a 4- to 8- hour window), nine trials.

The trials were short (mostly 5-12 weeks long) and small (10-150 participants), and mostly conducted in the United States. 

They found these strategies can all produce a mild to moderate 3%-8% weight loss during 8-12 weeks, similar to that attained with a calorie-restricted diet.

Some studies found that patients had improvements in blood pressure, LDL cholesterol, triglycerides, insulin resistance, and hemoglobin A1c.

These weight-loss strategies produced few gastrointestinal, neurological, hormonal, or metabolic adverse effects; “however, as adverse outcomes are not regularly assessed in human trials of fasting, definitive conclusions regarding the safety of these diets are difficult to draw at present,” the researchers caution.

Practical advice, great anecdotes

Typically, 1-2 weeks of adjustment is needed when individuals start intermittent fasting, the researchers say.

While following this eating pattern, patients should be encouraged to consume plenty of fruits, vegetables, and whole grains to boost their fiber and micronutrient intake.

On fasting days, they should consume at least 50 g of lean protein to help control hunger and prevent excessive loss of lean mass. On those days, alcohol is permitted but not recommended. Energy drinks and coffee or tea without sugar, milk, or cream are allowed, and diet soda should be limited to two servings a day because it can increase sugar cravings.

Ideally, clinicians should regularly assess patients for adverse effects during the first 3 months of intermittent fasting. They should also monitor patients for deficiencies in vitamin D, vitamin B₁₂, and electrolytes, as well as for changes in medications for blood pressure, lipids, and glucose that may be needed if patients lose weight.

Patients who reach their weight-loss goals and wish to stop intermittent fasting need to transition to a weight-maintenance program, possibly by increasing energy intake on fasting days to 1,000-1,200 kcal/day or widening the eating window to 12 hours in time-restricted eating.

“I get lots of emails from people saying that they have been on the diet for 10-15 years, and it reversed their type 2 diabetes, and they lost 60 pounds, and it was the only diet they could stick to,” Dr. Varady noted.

“That is always nice to hear, but we really do need long-term data to see if people can do intermittent fasting for the long term,” she reiterated.  

The review was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Varady received author fees from the Hachette Book Group for the book, “The Every Other Day Diet.” The other authors have declared no relevant financial relationships.

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

People who recover from a mild case of COVID-19 appear to have an increased risk for subsequent new-onset type 2 diabetes but not other types of diabetes, new data suggest.

“If confirmed, the results of the present study indicate that diabetes screening in individuals who have recovered from even mild COVID-19 should be recommended,” say Wolfgang Rathmann, MD, of the Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, and colleagues.

The findings, from a nationwide primary care database in Germany, were recently published in Diabetologia.

These primary care data align with those from other studies of more seriously ill patients with COVID-19 that found increased rates of type 2 diabetes diagnoses in the subsequent months following illness, they point out.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta-cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies sped it up,” said Dr. Rathmann in a press release.

However, because the patients with COVID-19 in the study were only followed for about 3 months, “further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered or whether it leads to a chronic condition,” he noted.
 

Increase in type 2 diabetes 3 months after mild COVID-19

The retrospective cohort analysis was performed using data from the Disease Analyzer, a representative panel of 1,171 physician practices in Germany, from March 2020 to January 2021, with follow-up through July 2021.

Individuals with a history of COVID-19 or diabetes and those taking corticosteroids within 30 days after the index dates were excluded.

A total of 35,865 patients with confirmed SARS-CoV-2 infection were propensity score-matched on a one-to-one basis for sex, age, health insurance, and comorbidities with those who had acute respiratory tract infections (controls) but were COVID-19 negative. Median follow-up was 119 days for the COVID-19 group and 161 days for controls.

There was a 28% increased risk of type 2 diabetes for those who had COVID-19 versus controls (15.8 per 1,000 person-years vs. 12.3 per 1,000 person-years, respectively, which was significantly different, and an incidence rate ratio of 1.28).

The incidence of other types of diabetes or unspecified diabetes for the COVID-19 and control groups did not differ significantly (4.3 per 1,000 person-years vs. 3.7 per 1,000 person-years; IRR, 1.17).

Similar findings were seen in sensitivity analyses by glucose-lowering medication prescriptions and by ICD-10 codes.

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

CoviDiab registry tracking type 1 and type 2 diabetes

Over the course of the pandemic, there have been conflicting data on whether COVID-19 induces or reveals a propensity for type 1 and type 2 diabetes.

The CoviDiab global registry is tracking this and will include diabetes type for adults and children.

The aim is to have “as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c,” coprincipal investigator Francesco Rubino, MD, of King’s College London, previously told this news organization.

“By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19.”

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or the hyperglycemia may be stress-induced and temporary.

The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. Dr. Rathmann has reported receiving consulting fees for attending educational sessions or advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk and institutional research grants from Novo Nordisk outside of the topic of the current work.

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

People who recover from a mild case of COVID-19 appear to have an increased risk for subsequent new-onset type 2 diabetes but not other types of diabetes, new data suggest.

“If confirmed, the results of the present study indicate that diabetes screening in individuals who have recovered from even mild COVID-19 should be recommended,” say Wolfgang Rathmann, MD, of the Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, and colleagues.

The findings, from a nationwide primary care database in Germany, were recently published in Diabetologia.

These primary care data align with those from other studies of more seriously ill patients with COVID-19 that found increased rates of type 2 diabetes diagnoses in the subsequent months following illness, they point out.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta-cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies sped it up,” said Dr. Rathmann in a press release.

However, because the patients with COVID-19 in the study were only followed for about 3 months, “further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered or whether it leads to a chronic condition,” he noted.
 

Increase in type 2 diabetes 3 months after mild COVID-19

The retrospective cohort analysis was performed using data from the Disease Analyzer, a representative panel of 1,171 physician practices in Germany, from March 2020 to January 2021, with follow-up through July 2021.

Individuals with a history of COVID-19 or diabetes and those taking corticosteroids within 30 days after the index dates were excluded.

A total of 35,865 patients with confirmed SARS-CoV-2 infection were propensity score-matched on a one-to-one basis for sex, age, health insurance, and comorbidities with those who had acute respiratory tract infections (controls) but were COVID-19 negative. Median follow-up was 119 days for the COVID-19 group and 161 days for controls.

There was a 28% increased risk of type 2 diabetes for those who had COVID-19 versus controls (15.8 per 1,000 person-years vs. 12.3 per 1,000 person-years, respectively, which was significantly different, and an incidence rate ratio of 1.28).

The incidence of other types of diabetes or unspecified diabetes for the COVID-19 and control groups did not differ significantly (4.3 per 1,000 person-years vs. 3.7 per 1,000 person-years; IRR, 1.17).

Similar findings were seen in sensitivity analyses by glucose-lowering medication prescriptions and by ICD-10 codes.

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

CoviDiab registry tracking type 1 and type 2 diabetes

Over the course of the pandemic, there have been conflicting data on whether COVID-19 induces or reveals a propensity for type 1 and type 2 diabetes.

The CoviDiab global registry is tracking this and will include diabetes type for adults and children.

The aim is to have “as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c,” coprincipal investigator Francesco Rubino, MD, of King’s College London, previously told this news organization.

“By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19.”

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or the hyperglycemia may be stress-induced and temporary.

The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. Dr. Rathmann has reported receiving consulting fees for attending educational sessions or advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk and institutional research grants from Novo Nordisk outside of the topic of the current work.

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

People who recover from a mild case of COVID-19 appear to have an increased risk for subsequent new-onset type 2 diabetes but not other types of diabetes, new data suggest.

“If confirmed, the results of the present study indicate that diabetes screening in individuals who have recovered from even mild COVID-19 should be recommended,” say Wolfgang Rathmann, MD, of the Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, and colleagues.

The findings, from a nationwide primary care database in Germany, were recently published in Diabetologia.

These primary care data align with those from other studies of more seriously ill patients with COVID-19 that found increased rates of type 2 diabetes diagnoses in the subsequent months following illness, they point out.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta-cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies sped it up,” said Dr. Rathmann in a press release.

However, because the patients with COVID-19 in the study were only followed for about 3 months, “further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered or whether it leads to a chronic condition,” he noted.
 

Increase in type 2 diabetes 3 months after mild COVID-19

The retrospective cohort analysis was performed using data from the Disease Analyzer, a representative panel of 1,171 physician practices in Germany, from March 2020 to January 2021, with follow-up through July 2021.

Individuals with a history of COVID-19 or diabetes and those taking corticosteroids within 30 days after the index dates were excluded.

A total of 35,865 patients with confirmed SARS-CoV-2 infection were propensity score-matched on a one-to-one basis for sex, age, health insurance, and comorbidities with those who had acute respiratory tract infections (controls) but were COVID-19 negative. Median follow-up was 119 days for the COVID-19 group and 161 days for controls.

There was a 28% increased risk of type 2 diabetes for those who had COVID-19 versus controls (15.8 per 1,000 person-years vs. 12.3 per 1,000 person-years, respectively, which was significantly different, and an incidence rate ratio of 1.28).

The incidence of other types of diabetes or unspecified diabetes for the COVID-19 and control groups did not differ significantly (4.3 per 1,000 person-years vs. 3.7 per 1,000 person-years; IRR, 1.17).

Similar findings were seen in sensitivity analyses by glucose-lowering medication prescriptions and by ICD-10 codes.

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

CoviDiab registry tracking type 1 and type 2 diabetes

Over the course of the pandemic, there have been conflicting data on whether COVID-19 induces or reveals a propensity for type 1 and type 2 diabetes.

The CoviDiab global registry is tracking this and will include diabetes type for adults and children.

The aim is to have “as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c,” coprincipal investigator Francesco Rubino, MD, of King’s College London, previously told this news organization.

“By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19.”

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or the hyperglycemia may be stress-induced and temporary.

The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. Dr. Rathmann has reported receiving consulting fees for attending educational sessions or advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk and institutional research grants from Novo Nordisk outside of the topic of the current work.

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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