Clinical Endocrinology News

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

People with diabetes who live in small towns in the United States experience higher rates of complications than those living in cities and remote areas.

METHODOLOGY:

Retrospective cohort study using the OptumLabs Data Warehouse used a deidentified data set of US commercial and Medicare Advantage beneficiaries including 2,901,563 adults with diabetes between 2012 and 2021.

Overall, 2.6% lived in remote areas (population < 2500), 14.1% in small towns (2500-50,000), and 83.3% in cities (> 50,000).

Multivariable analysis adjusted for age, sex, health plan type, index year, diabetes type, baseline comorbidities, and medication use.

TAKEAWAY:

Relative to people living in cities, people in remote areas had significantly greater risks for myocardial infarction (hazard ratio, 1.06) and revascularization (1.04) but lower risks for hypoglycemia (0.90) and stroke (0.91).

Compared with cities, people living in small towns had significantly more hyperglycemia (1.06), hypoglycemia (1.15), end-stage kidney disease (1.04), myocardial infarction (1.10), heart failure (1.05), amputation (1.05), other lower-extremity complications (1.02), and revascularization (1.05), but a lower risk for stroke (0.95).

Compared with small towns, people living in remote areas had lower risks for hyperglycemia (0.85), hypoglycemia (0.92), and heart failure (0.94).

No geographic differences were found for retinopathy or atrial fibrillation/flutter.

The results didn’t differ significantly when the 2.5% overall with type 1 diabetes were removed from the dataset.

IN PRACTICE:

“While more research is needed to better understand the underlying causes of disparate diabetes outcomes along the rural-urban continuum, this study establishes the foundational differences to guide improvement efforts and helps to identify complications with the greatest disparities to which policy interventions may be targeted.”

SOURCE:

The study was conducted by Kyle Steiger, MD, Internal Medicine Residency, Mayo Clinic, Rochester, Minnesota, and colleagues, and published February 22 in Diabetes Care.

LIMITATIONS:

Claims data were from a single national health insurance provider that administers multiple private and Medicare Advantage health plans with disproportionate representation of urban populations and without people who have Medicaid or traditional Medicare fee-for-service or who are without insurance (and would be expected to have higher complication rates). There were no data on race/ethnicity. Potential for residual confounding.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Steiger had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

People with diabetes who live in small towns in the United States experience higher rates of complications than those living in cities and remote areas.

METHODOLOGY:

Retrospective cohort study using the OptumLabs Data Warehouse used a deidentified data set of US commercial and Medicare Advantage beneficiaries including 2,901,563 adults with diabetes between 2012 and 2021.

Overall, 2.6% lived in remote areas (population < 2500), 14.1% in small towns (2500-50,000), and 83.3% in cities (> 50,000).

Multivariable analysis adjusted for age, sex, health plan type, index year, diabetes type, baseline comorbidities, and medication use.

TAKEAWAY:

Relative to people living in cities, people in remote areas had significantly greater risks for myocardial infarction (hazard ratio, 1.06) and revascularization (1.04) but lower risks for hypoglycemia (0.90) and stroke (0.91).

Compared with cities, people living in small towns had significantly more hyperglycemia (1.06), hypoglycemia (1.15), end-stage kidney disease (1.04), myocardial infarction (1.10), heart failure (1.05), amputation (1.05), other lower-extremity complications (1.02), and revascularization (1.05), but a lower risk for stroke (0.95).

Compared with small towns, people living in remote areas had lower risks for hyperglycemia (0.85), hypoglycemia (0.92), and heart failure (0.94).

No geographic differences were found for retinopathy or atrial fibrillation/flutter.

The results didn’t differ significantly when the 2.5% overall with type 1 diabetes were removed from the dataset.

IN PRACTICE:

“While more research is needed to better understand the underlying causes of disparate diabetes outcomes along the rural-urban continuum, this study establishes the foundational differences to guide improvement efforts and helps to identify complications with the greatest disparities to which policy interventions may be targeted.”

SOURCE:

The study was conducted by Kyle Steiger, MD, Internal Medicine Residency, Mayo Clinic, Rochester, Minnesota, and colleagues, and published February 22 in Diabetes Care.

LIMITATIONS:

Claims data were from a single national health insurance provider that administers multiple private and Medicare Advantage health plans with disproportionate representation of urban populations and without people who have Medicaid or traditional Medicare fee-for-service or who are without insurance (and would be expected to have higher complication rates). There were no data on race/ethnicity. Potential for residual confounding.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Steiger had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

People with diabetes who live in small towns in the United States experience higher rates of complications than those living in cities and remote areas.

METHODOLOGY:

Retrospective cohort study using the OptumLabs Data Warehouse used a deidentified data set of US commercial and Medicare Advantage beneficiaries including 2,901,563 adults with diabetes between 2012 and 2021.

Overall, 2.6% lived in remote areas (population < 2500), 14.1% in small towns (2500-50,000), and 83.3% in cities (> 50,000).

Multivariable analysis adjusted for age, sex, health plan type, index year, diabetes type, baseline comorbidities, and medication use.

TAKEAWAY:

Relative to people living in cities, people in remote areas had significantly greater risks for myocardial infarction (hazard ratio, 1.06) and revascularization (1.04) but lower risks for hypoglycemia (0.90) and stroke (0.91).

Compared with cities, people living in small towns had significantly more hyperglycemia (1.06), hypoglycemia (1.15), end-stage kidney disease (1.04), myocardial infarction (1.10), heart failure (1.05), amputation (1.05), other lower-extremity complications (1.02), and revascularization (1.05), but a lower risk for stroke (0.95).

Compared with small towns, people living in remote areas had lower risks for hyperglycemia (0.85), hypoglycemia (0.92), and heart failure (0.94).

No geographic differences were found for retinopathy or atrial fibrillation/flutter.

The results didn’t differ significantly when the 2.5% overall with type 1 diabetes were removed from the dataset.

IN PRACTICE:

“While more research is needed to better understand the underlying causes of disparate diabetes outcomes along the rural-urban continuum, this study establishes the foundational differences to guide improvement efforts and helps to identify complications with the greatest disparities to which policy interventions may be targeted.”

SOURCE:

The study was conducted by Kyle Steiger, MD, Internal Medicine Residency, Mayo Clinic, Rochester, Minnesota, and colleagues, and published February 22 in Diabetes Care.

LIMITATIONS:

Claims data were from a single national health insurance provider that administers multiple private and Medicare Advantage health plans with disproportionate representation of urban populations and without people who have Medicaid or traditional Medicare fee-for-service or who are without insurance (and would be expected to have higher complication rates). There were no data on race/ethnicity. Potential for residual confounding.

DISCLOSURES:

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Steiger had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk of developing gynecologic cancer is lower in women with hyperthyroidism than in those without it, found a large study. 

METHODOLOGY:

• Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
• This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
• Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
• The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.

TAKEAWAY:

• Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
• The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
• The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
• A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.

IN PRACTICE:

The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.

SOURCE:

This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.

LIMITATIONS:

The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.

DISCLOSURES:

This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk of developing gynecologic cancer is lower in women with hyperthyroidism than in those without it, found a large study. 

METHODOLOGY:

• Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
• This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
• Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
• The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.

TAKEAWAY:

• Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
• The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
• The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
• A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.

IN PRACTICE:

The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.

SOURCE:

This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.

LIMITATIONS:

The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.

DISCLOSURES:

This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk of developing gynecologic cancer is lower in women with hyperthyroidism than in those without it, found a large study. 

METHODOLOGY:

• Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
• This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
• Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
• The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.

TAKEAWAY:

• Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
• The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
• The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
• A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.

IN PRACTICE:

The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.

SOURCE:

This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.

LIMITATIONS:

The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.

DISCLOSURES:

This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.