Diabetes

Fewer than 10% of American adults with type 2 diabetes who qualified for treatment with newer agents – such as an SGLT2 inhibitor or GLP-1 agonist – actually received treatment with at least one drug from drug class in 2017-2020, based on a new analysis of just over a thousand adults who participated in a representative, biannual survey and self-reported a diabetes diagnosis.

The cost of these agents, and their uncertain cost-effectiveness at current prices, is likely a key driver of the low usage rate, say the authors of a brief report published in Annals of Internal Medicine.

“Clinical studies have shown that both GLP-1 [glucagonlike peptide–1] receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors yield additional clinical benefits, compared with older treatments in reducing body weight and progression of cardiovascular disease and chronic kidney disease,” write Shichao Tang, PhD, from the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues.

“However, these medications come at a substantially higher cost,” they stress.

Dr. Tang explained in an interview that the new study “points to prior studies about the high cost of these medications as a potential barrier to use, but more research is needed to understand cost-effectiveness and any potential barriers to use, including cost.”

The work “did not include research into cost-effectiveness or why the percentage of people already using these medications was low,” he emphasized.

Dr. Tang and colleagues used data collected by the U.S. National Health and Nutrition Examination Survey during two 2-year cycles between 2017 and 2020 that included 1,417 people who self-identified a diagnosis of diabetes.

Excluding those who likely had type 1 diabetes and those with incomplete data left 1,330 survey participants, including 1,133 (85%) who fit criteria for the treatment of type 2 diabetes with an agent from one of the two studied classes, as recommended in 2022 by a panel representing the American Diabetes Association and the European Association for the Study of Diabetes.

Among these 1,133 people – who represent more than 22 million American adults with type 2 diabetes who fit the 2022 criteria – a scant 3.7% were actually taking a GLP-1 agonist and 5.3% were taking an SGLT2 inhibitor.

“While it’s important to note that our data predate the 2022 recommendations, these drugs were offered as second-line therapy for patients with certain diabetes-related complications in 2017-2020” and hence provide potentially useful insights, noted Dr. Tang, a health economist with the CDC National Center for Chronic Disease Prevention and Health Promotion.

Based on retail prices listed on a United States–based website, a 30-day supply of an oral SGLT2 inhibitor can cost about $550-$600 per month, while common subcutaneously injected GLP-1 receptor agonists can run from a few hundred dollars for a daily injection or close to $1,000 for a formulation administered weekly.

“Cost-effectiveness was not formally considered in the current guideline, but an assessment of cost-effectiveness may assist better targeting of interventions to achieve the greatest effect at a sustainable cost,” the researchers conclude.

The study received no commercial funding. None of the authors had relevant financial relationships.

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

Fewer than 10% of American adults with type 2 diabetes who qualified for treatment with newer agents – such as an SGLT2 inhibitor or GLP-1 agonist – actually received treatment with at least one drug from drug class in 2017-2020, based on a new analysis of just over a thousand adults who participated in a representative, biannual survey and self-reported a diabetes diagnosis.

The cost of these agents, and their uncertain cost-effectiveness at current prices, is likely a key driver of the low usage rate, say the authors of a brief report published in Annals of Internal Medicine.

“Clinical studies have shown that both GLP-1 [glucagonlike peptide–1] receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors yield additional clinical benefits, compared with older treatments in reducing body weight and progression of cardiovascular disease and chronic kidney disease,” write Shichao Tang, PhD, from the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues.

“However, these medications come at a substantially higher cost,” they stress.

Dr. Tang explained in an interview that the new study “points to prior studies about the high cost of these medications as a potential barrier to use, but more research is needed to understand cost-effectiveness and any potential barriers to use, including cost.”

The work “did not include research into cost-effectiveness or why the percentage of people already using these medications was low,” he emphasized.

Dr. Tang and colleagues used data collected by the U.S. National Health and Nutrition Examination Survey during two 2-year cycles between 2017 and 2020 that included 1,417 people who self-identified a diagnosis of diabetes.

Excluding those who likely had type 1 diabetes and those with incomplete data left 1,330 survey participants, including 1,133 (85%) who fit criteria for the treatment of type 2 diabetes with an agent from one of the two studied classes, as recommended in 2022 by a panel representing the American Diabetes Association and the European Association for the Study of Diabetes.

Among these 1,133 people – who represent more than 22 million American adults with type 2 diabetes who fit the 2022 criteria – a scant 3.7% were actually taking a GLP-1 agonist and 5.3% were taking an SGLT2 inhibitor.

“While it’s important to note that our data predate the 2022 recommendations, these drugs were offered as second-line therapy for patients with certain diabetes-related complications in 2017-2020” and hence provide potentially useful insights, noted Dr. Tang, a health economist with the CDC National Center for Chronic Disease Prevention and Health Promotion.

Based on retail prices listed on a United States–based website, a 30-day supply of an oral SGLT2 inhibitor can cost about $550-$600 per month, while common subcutaneously injected GLP-1 receptor agonists can run from a few hundred dollars for a daily injection or close to $1,000 for a formulation administered weekly.

“Cost-effectiveness was not formally considered in the current guideline, but an assessment of cost-effectiveness may assist better targeting of interventions to achieve the greatest effect at a sustainable cost,” the researchers conclude.

The study received no commercial funding. None of the authors had relevant financial relationships.

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

Fewer than 10% of American adults with type 2 diabetes who qualified for treatment with newer agents – such as an SGLT2 inhibitor or GLP-1 agonist – actually received treatment with at least one drug from drug class in 2017-2020, based on a new analysis of just over a thousand adults who participated in a representative, biannual survey and self-reported a diabetes diagnosis.

The cost of these agents, and their uncertain cost-effectiveness at current prices, is likely a key driver of the low usage rate, say the authors of a brief report published in Annals of Internal Medicine.

“Clinical studies have shown that both GLP-1 [glucagonlike peptide–1] receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors yield additional clinical benefits, compared with older treatments in reducing body weight and progression of cardiovascular disease and chronic kidney disease,” write Shichao Tang, PhD, from the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues.

“However, these medications come at a substantially higher cost,” they stress.

Dr. Tang explained in an interview that the new study “points to prior studies about the high cost of these medications as a potential barrier to use, but more research is needed to understand cost-effectiveness and any potential barriers to use, including cost.”

The work “did not include research into cost-effectiveness or why the percentage of people already using these medications was low,” he emphasized.

Dr. Tang and colleagues used data collected by the U.S. National Health and Nutrition Examination Survey during two 2-year cycles between 2017 and 2020 that included 1,417 people who self-identified a diagnosis of diabetes.

Excluding those who likely had type 1 diabetes and those with incomplete data left 1,330 survey participants, including 1,133 (85%) who fit criteria for the treatment of type 2 diabetes with an agent from one of the two studied classes, as recommended in 2022 by a panel representing the American Diabetes Association and the European Association for the Study of Diabetes.

Among these 1,133 people – who represent more than 22 million American adults with type 2 diabetes who fit the 2022 criteria – a scant 3.7% were actually taking a GLP-1 agonist and 5.3% were taking an SGLT2 inhibitor.

“While it’s important to note that our data predate the 2022 recommendations, these drugs were offered as second-line therapy for patients with certain diabetes-related complications in 2017-2020” and hence provide potentially useful insights, noted Dr. Tang, a health economist with the CDC National Center for Chronic Disease Prevention and Health Promotion.

Based on retail prices listed on a United States–based website, a 30-day supply of an oral SGLT2 inhibitor can cost about $550-$600 per month, while common subcutaneously injected GLP-1 receptor agonists can run from a few hundred dollars for a daily injection or close to $1,000 for a formulation administered weekly.

“Cost-effectiveness was not formally considered in the current guideline, but an assessment of cost-effectiveness may assist better targeting of interventions to achieve the greatest effect at a sustainable cost,” the researchers conclude.

The study received no commercial funding. None of the authors had relevant financial relationships.

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

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

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

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

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

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

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

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

Youth with type 1 diabetes who use real-time continuous glucose monitoring (rtCGM) and an insulin pump spend more time in target glucose range than do those using intermittently scanned CGM (isCGM) and/or multiple daily insulin injections, new data show.

In the multinational cohort study of more than 4,500 people younger than age 21 with type 1 diabetes, those using rtCGM and pumps also spent less time above and below glucose targets and had fewer severe adverse events – either severe hypoglycemia or diabetic ketoacidosis (DKA) – compared with injections and isCGM.

Daria Nipot/Getty Images

The findings were published online in JAMA Network Open by Klemen Dovc, MD, PhD, assistant professor in the department of pediatric endocrinology, diabetes, and metabolic diseases, University Children’s Hospital, Ljubljana, Slovenia, and colleagues.

“These results underscore the synergistic effect of advanced diabetes technologies that should be more readily available to youths with type 1 diabetes for further improvement of diabetes-related clinical outcomes,” the authors wrote.

Moreover, Dr. Dovc told this news organization: “Clinicians should be aware that there may be differences in effectiveness between different types of devices, and that choosing the right device for each individual may be important for achieving optimal outcomes.”
 

Real-time CGM + insulin pump = highest time in range

The researchers explained that two modalities of CGM are broadly available: rtCGM, which continuously displays glucose concentration in the interstitial fluid (usually at intervals of 1-5 minutes) on a dedicated receiver or other portable device, such as a smartphone, and provides various adjustable alarms, and isCGM, which displays data on demand when the transmitter is scanned using either a dedicated reader or smartphone-based application.

rtCGMs include devices from Dexcom and Medtronic. The isCGM, or “flash,” generally refers to the Abbott FreeStyle Libre.

The study included individuals younger than 21 years from 34 centers in 21 countries in the SWEET registry, a worldwide network of diabetes care centers for youth, between Jan. 1, 2016, and Dec. 31, 2021.

The researchers didn’t report which particular devices were used in the trial, rather they just divided patients into four groups: 850 used isCGM with a pump, 1,231 used isCGM with multiple daily injections, 2,252 used rtCGM with a pump, and 886 used rtCGM with insulin injections.

After adjustments for sex, age, diabetes duration, and body mass index standard deviation score, rtCGM plus insulin pump was the most likely group to achieve the recommended greater than 70% time in target glycemic range (70-180 mg/dL), with 36.2% achieving it, followed by rtCGM plus injections, at 20.9%, and isCGM plus injections, at 12.5%. Those using isCGM with an insulin pump were the least likely to achieve time in range, at just 11.3%.

Similar trends were seen for the recommended goal of less than 4% of time spent below range (< 70 mg/dL) and less than 25% of time spent above range (> 180 mg/dL). Those using rtCGM with a pump had the highest proportions achieving both of those goals, 73.1% and 32.5%, respectively.  

The use of rtCGM, with or without a pump, was associated with lower rates of severe hypoglycemia (2.5% and 2.0%, respectively) than isCGM with or without a pump (5.5% and 5.2%, respectively).

Similarly, the proportion experiencing at least one DKA episode varied from 1.4% for rtCGM plus insulin pump and 0.7% for rtCGM plus injections to 3.0% for isCGM plus pump and 1.5% isCGM plus injections.


 

Study looked at older technology but results still reflect benefit

Among the rtCGM plus insulin pump group were 264 participants (5% of the total study population) recorded in the database as using automated insulin delivery (AID) systems, also known as the artificial pancreas, although this is likely an undercount as the presence of communication between the two devices was not automatically recorded, Dr. Dovc explained.

Those individuals recorded as using AIDs had a higher unadjusted time in range compared with non-AID users (66.3% vs. 59.0%) and lower time above range (30.1% vs. 37.0%) but didn’t differ in time below range (2.9% vs. 3.0%).

Dr. Dovc told this news organization: “While automated systems are becoming more common, there are still many individuals who do not have access to glucose-responsive devices.” Reasons include lack of reimbursement, or decisions not to use them, he said.

But, he added, “Despite the low reported numbers of AID users, results achieved in the pump with real-time CGM [group] are admirable and approaching recommended consensus targets with a clinically meaningful difference towards all other treatment modalities. As our findings may not be directly applicable to all participants using automated systems, they may still provide useful insights into the factors that influence glycemic control.”

Similarly, the intermittently scanned CGMs used by most in the study, and particularly in the earlier period, didn’t have low- or high-glucose alarms as do later versions. And an even more recent version also doesn’t require scanning either, so is essentially also “real-time.”

Dr. Dovc noted, “in the first half of our observational period only first generation of intermittently-scanned CGM was generally available, and we can speculate that only a small proportion started to use second generation towards the end of our observational period. The exact number of second-generation users was not available in this analysis.”

He acknowledged that because the study was observational and not randomized, patient choice of device could have influenced the outcomes.

“For example, participants who choose to use a more expensive device may have more resources or support available to them, which could influence their ability to manage their diabetes effectively. Additionally, individuals who choose to use a particular device may be more motivated or engaged in their diabetes care, which could also impact their outcomes. It would be important for future studies to explore the impact of device selection on device effectiveness and to control for this potential confounding factor in the analysis.”

This study was supported by the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) corporate members, including Abbott Laboratories, Boehringer Ingelheim, Dexcom, Insulet, Eli Lilly, Medtronic, Sanofi, and the Slovenian National Research Agency. Dr. Dovc disclosed ties with Abbott Laboratories, Medtronic, Novo Nordisk, Eli Lilly, and Pfizer. He served as a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes.   

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

Youth with type 1 diabetes who use real-time continuous glucose monitoring (rtCGM) and an insulin pump spend more time in target glucose range than do those using intermittently scanned CGM (isCGM) and/or multiple daily insulin injections, new data show.

In the multinational cohort study of more than 4,500 people younger than age 21 with type 1 diabetes, those using rtCGM and pumps also spent less time above and below glucose targets and had fewer severe adverse events – either severe hypoglycemia or diabetic ketoacidosis (DKA) – compared with injections and isCGM.

Daria Nipot/Getty Images

The findings were published online in JAMA Network Open by Klemen Dovc, MD, PhD, assistant professor in the department of pediatric endocrinology, diabetes, and metabolic diseases, University Children’s Hospital, Ljubljana, Slovenia, and colleagues.

“These results underscore the synergistic effect of advanced diabetes technologies that should be more readily available to youths with type 1 diabetes for further improvement of diabetes-related clinical outcomes,” the authors wrote.

Moreover, Dr. Dovc told this news organization: “Clinicians should be aware that there may be differences in effectiveness between different types of devices, and that choosing the right device for each individual may be important for achieving optimal outcomes.”
 

Real-time CGM + insulin pump = highest time in range

The researchers explained that two modalities of CGM are broadly available: rtCGM, which continuously displays glucose concentration in the interstitial fluid (usually at intervals of 1-5 minutes) on a dedicated receiver or other portable device, such as a smartphone, and provides various adjustable alarms, and isCGM, which displays data on demand when the transmitter is scanned using either a dedicated reader or smartphone-based application.

rtCGMs include devices from Dexcom and Medtronic. The isCGM, or “flash,” generally refers to the Abbott FreeStyle Libre.

The study included individuals younger than 21 years from 34 centers in 21 countries in the SWEET registry, a worldwide network of diabetes care centers for youth, between Jan. 1, 2016, and Dec. 31, 2021.

The researchers didn’t report which particular devices were used in the trial, rather they just divided patients into four groups: 850 used isCGM with a pump, 1,231 used isCGM with multiple daily injections, 2,252 used rtCGM with a pump, and 886 used rtCGM with insulin injections.

After adjustments for sex, age, diabetes duration, and body mass index standard deviation score, rtCGM plus insulin pump was the most likely group to achieve the recommended greater than 70% time in target glycemic range (70-180 mg/dL), with 36.2% achieving it, followed by rtCGM plus injections, at 20.9%, and isCGM plus injections, at 12.5%. Those using isCGM with an insulin pump were the least likely to achieve time in range, at just 11.3%.

Similar trends were seen for the recommended goal of less than 4% of time spent below range (< 70 mg/dL) and less than 25% of time spent above range (> 180 mg/dL). Those using rtCGM with a pump had the highest proportions achieving both of those goals, 73.1% and 32.5%, respectively.  

The use of rtCGM, with or without a pump, was associated with lower rates of severe hypoglycemia (2.5% and 2.0%, respectively) than isCGM with or without a pump (5.5% and 5.2%, respectively).

Similarly, the proportion experiencing at least one DKA episode varied from 1.4% for rtCGM plus insulin pump and 0.7% for rtCGM plus injections to 3.0% for isCGM plus pump and 1.5% isCGM plus injections.


 

Study looked at older technology but results still reflect benefit

Among the rtCGM plus insulin pump group were 264 participants (5% of the total study population) recorded in the database as using automated insulin delivery (AID) systems, also known as the artificial pancreas, although this is likely an undercount as the presence of communication between the two devices was not automatically recorded, Dr. Dovc explained.

Those individuals recorded as using AIDs had a higher unadjusted time in range compared with non-AID users (66.3% vs. 59.0%) and lower time above range (30.1% vs. 37.0%) but didn’t differ in time below range (2.9% vs. 3.0%).

Dr. Dovc told this news organization: “While automated systems are becoming more common, there are still many individuals who do not have access to glucose-responsive devices.” Reasons include lack of reimbursement, or decisions not to use them, he said.

But, he added, “Despite the low reported numbers of AID users, results achieved in the pump with real-time CGM [group] are admirable and approaching recommended consensus targets with a clinically meaningful difference towards all other treatment modalities. As our findings may not be directly applicable to all participants using automated systems, they may still provide useful insights into the factors that influence glycemic control.”

Similarly, the intermittently scanned CGMs used by most in the study, and particularly in the earlier period, didn’t have low- or high-glucose alarms as do later versions. And an even more recent version also doesn’t require scanning either, so is essentially also “real-time.”

Dr. Dovc noted, “in the first half of our observational period only first generation of intermittently-scanned CGM was generally available, and we can speculate that only a small proportion started to use second generation towards the end of our observational period. The exact number of second-generation users was not available in this analysis.”

He acknowledged that because the study was observational and not randomized, patient choice of device could have influenced the outcomes.

“For example, participants who choose to use a more expensive device may have more resources or support available to them, which could influence their ability to manage their diabetes effectively. Additionally, individuals who choose to use a particular device may be more motivated or engaged in their diabetes care, which could also impact their outcomes. It would be important for future studies to explore the impact of device selection on device effectiveness and to control for this potential confounding factor in the analysis.”

This study was supported by the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) corporate members, including Abbott Laboratories, Boehringer Ingelheim, Dexcom, Insulet, Eli Lilly, Medtronic, Sanofi, and the Slovenian National Research Agency. Dr. Dovc disclosed ties with Abbott Laboratories, Medtronic, Novo Nordisk, Eli Lilly, and Pfizer. He served as a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes.   

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

Youth with type 1 diabetes who use real-time continuous glucose monitoring (rtCGM) and an insulin pump spend more time in target glucose range than do those using intermittently scanned CGM (isCGM) and/or multiple daily insulin injections, new data show.

In the multinational cohort study of more than 4,500 people younger than age 21 with type 1 diabetes, those using rtCGM and pumps also spent less time above and below glucose targets and had fewer severe adverse events – either severe hypoglycemia or diabetic ketoacidosis (DKA) – compared with injections and isCGM.

Daria Nipot/Getty Images

The findings were published online in JAMA Network Open by Klemen Dovc, MD, PhD, assistant professor in the department of pediatric endocrinology, diabetes, and metabolic diseases, University Children’s Hospital, Ljubljana, Slovenia, and colleagues.

“These results underscore the synergistic effect of advanced diabetes technologies that should be more readily available to youths with type 1 diabetes for further improvement of diabetes-related clinical outcomes,” the authors wrote.

Moreover, Dr. Dovc told this news organization: “Clinicians should be aware that there may be differences in effectiveness between different types of devices, and that choosing the right device for each individual may be important for achieving optimal outcomes.”
 

Real-time CGM + insulin pump = highest time in range

The researchers explained that two modalities of CGM are broadly available: rtCGM, which continuously displays glucose concentration in the interstitial fluid (usually at intervals of 1-5 minutes) on a dedicated receiver or other portable device, such as a smartphone, and provides various adjustable alarms, and isCGM, which displays data on demand when the transmitter is scanned using either a dedicated reader or smartphone-based application.

rtCGMs include devices from Dexcom and Medtronic. The isCGM, or “flash,” generally refers to the Abbott FreeStyle Libre.

The study included individuals younger than 21 years from 34 centers in 21 countries in the SWEET registry, a worldwide network of diabetes care centers for youth, between Jan. 1, 2016, and Dec. 31, 2021.

The researchers didn’t report which particular devices were used in the trial, rather they just divided patients into four groups: 850 used isCGM with a pump, 1,231 used isCGM with multiple daily injections, 2,252 used rtCGM with a pump, and 886 used rtCGM with insulin injections.

After adjustments for sex, age, diabetes duration, and body mass index standard deviation score, rtCGM plus insulin pump was the most likely group to achieve the recommended greater than 70% time in target glycemic range (70-180 mg/dL), with 36.2% achieving it, followed by rtCGM plus injections, at 20.9%, and isCGM plus injections, at 12.5%. Those using isCGM with an insulin pump were the least likely to achieve time in range, at just 11.3%.

Similar trends were seen for the recommended goal of less than 4% of time spent below range (< 70 mg/dL) and less than 25% of time spent above range (> 180 mg/dL). Those using rtCGM with a pump had the highest proportions achieving both of those goals, 73.1% and 32.5%, respectively.  

The use of rtCGM, with or without a pump, was associated with lower rates of severe hypoglycemia (2.5% and 2.0%, respectively) than isCGM with or without a pump (5.5% and 5.2%, respectively).

Similarly, the proportion experiencing at least one DKA episode varied from 1.4% for rtCGM plus insulin pump and 0.7% for rtCGM plus injections to 3.0% for isCGM plus pump and 1.5% isCGM plus injections.


 

Study looked at older technology but results still reflect benefit

Among the rtCGM plus insulin pump group were 264 participants (5% of the total study population) recorded in the database as using automated insulin delivery (AID) systems, also known as the artificial pancreas, although this is likely an undercount as the presence of communication between the two devices was not automatically recorded, Dr. Dovc explained.

Those individuals recorded as using AIDs had a higher unadjusted time in range compared with non-AID users (66.3% vs. 59.0%) and lower time above range (30.1% vs. 37.0%) but didn’t differ in time below range (2.9% vs. 3.0%).

Dr. Dovc told this news organization: “While automated systems are becoming more common, there are still many individuals who do not have access to glucose-responsive devices.” Reasons include lack of reimbursement, or decisions not to use them, he said.

But, he added, “Despite the low reported numbers of AID users, results achieved in the pump with real-time CGM [group] are admirable and approaching recommended consensus targets with a clinically meaningful difference towards all other treatment modalities. As our findings may not be directly applicable to all participants using automated systems, they may still provide useful insights into the factors that influence glycemic control.”

Similarly, the intermittently scanned CGMs used by most in the study, and particularly in the earlier period, didn’t have low- or high-glucose alarms as do later versions. And an even more recent version also doesn’t require scanning either, so is essentially also “real-time.”

Dr. Dovc noted, “in the first half of our observational period only first generation of intermittently-scanned CGM was generally available, and we can speculate that only a small proportion started to use second generation towards the end of our observational period. The exact number of second-generation users was not available in this analysis.”

He acknowledged that because the study was observational and not randomized, patient choice of device could have influenced the outcomes.

“For example, participants who choose to use a more expensive device may have more resources or support available to them, which could influence their ability to manage their diabetes effectively. Additionally, individuals who choose to use a particular device may be more motivated or engaged in their diabetes care, which could also impact their outcomes. It would be important for future studies to explore the impact of device selection on device effectiveness and to control for this potential confounding factor in the analysis.”

This study was supported by the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) corporate members, including Abbott Laboratories, Boehringer Ingelheim, Dexcom, Insulet, Eli Lilly, Medtronic, Sanofi, and the Slovenian National Research Agency. Dr. Dovc disclosed ties with Abbott Laboratories, Medtronic, Novo Nordisk, Eli Lilly, and Pfizer. He served as a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes.   

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

One-eyed, one-horned, flying purple veggie eater

Big Fruits and Vegetables is at it again. You notice how they’re always like “Oh, vegetables are good for your health,” and “Eating fruits every day makes you live longer,” but come on. It’s a marketing ploy, leading us astray from our personal savior, McDonald’s.

PxHere

Just look at this latest bit of research: According to researchers from Finland, eating purple vegetables can protect against diabetes. Considering nearly 40 million Americans have diabetes (and nearly 100 million have prediabetes), anything to reduce the incidence of diabetes (people with diabetes account for one-fourth of every dollar spent in U.S. health care) would be beneficial. So, let’s humor the fruits and veggies people this time and hear them out.

It all comes down to a chemical called anthocyanin, which is a pigment that gives fruits and vegetables such as blueberries, radishes, and red cabbages their purplish color. Anthocyanin also has probiotic and anti-inflammatory effects, meaning it can help improve intestinal lining health and regulate glucose and lipid metabolic pathways. Obviously, good things if you want to avoid diabetes.

The investigators also found that, while standard anthocyanin was beneficial, acylated anthocyanin (which has an acyl group added to the sugar molecules of anthocyanin) is really what you want to go for. The acylated version, found in abundance in purple potatoes, purple carrots, radishes, and red cabbages, is tougher to digest, but the positive effects it has in the body are enhanced over the standard version.

Now, this all a compelling bit of research, but at the end of the day, you’re still eating fruits and vegetables, and we are red-blooded Americans here. We don’t do healthy foods. Although, if you were to dye our burgers with anthocyanin and make them purple, you’d have our attention. Purple is our favorite color.
 

Manuka honey better as building material than antibiotic

Milk, according to the old saying, builds strong bones, but when it comes to patients with bone loss caused by various medical reasons, researchers found that manuka honey, produced only in New Zealand and some parts of Australia, may also do the job. They soaked collagen scaffolds used for bone implants in various concentrations of the honey and found that 5% led to higher mineral formation and osteoprotegerin production, which suggests increased bone production.

Marley Dewey

But, and this is a pretty big one, the other half of the study – testing manuka honey’s ability to ward off bacteria – wasn’t so successful. Bone implants, apparently, count for almost half of all hospital-acquired infections, which obviously can put a damper on the healing process. The hope was that a biomaterial would be more effective than something like metal in lessening bacteria formation. Nope.

When the researchers soaked paper disks in honey and added them to cultures of Pseudomonas aeruginosa and Staphylococcus aureus, none of the various concentrations stopped bacterial growth in the scaffolding, even when they added antibiotics.

The sticky conclusion, you could say, is more bitter than sweet.
 

It may sound like Korn, but can it play ‘Freak on a Leash’?

Like all right-thinking Americans, we love corn, corn-based products, and almost corn. Corn on the cob grilled in the husk? Mmm. Plus, we’re big fans of the band Korn. Also, we once had a reporter here named Tim Kirn. And don’t even get us started with Karn. Best Family Feud host ever.

Quorn

But what about Quorn? Oh sure, the fungi-based meat alternative is full of yummy mycoprotein, but can it prevent colorectal cancer? Can we add Quorn to our favorites list? Let’s see what Science has to say.

Researchers at Northumbria University in Newcastle upon Tyne, England, fed a group of 20 men some meat (240 g/day) for 2 weeks – hopefully, they were allowed to eat some other food as well – and then gave them the same amount of Quorn, excuse us, fungi-derived mycoprotein equivalents, for 2 more weeks, with a 4-week washout period in between.

Levels of cancer-causing chemicals known as genotoxins fell significantly in the mycoprotein phase but rose during the meat phase. The mycoprotein diet also improved gut health “by increasing the abundance of protective bacteria such as Lactobacilli, Roseburia, and Akkermansia, which are associated with offering protection against chemically induced tumours, inflammation and bowel cancer,” they said in a statement from the university.

The meat phase, on the other hand, resulted in an increase in “gut bacteria linked with issues such as cancer, cardiovascular diseases, weight gain and other negative health outcomes,” they noted.

Science, then, seems to approve of Quorn, and that’s good enough for us. We’re adding Quorn to our diet, starting with a fungi-derived mycoproteinburger tonight while we’re watching the Cornell Big Red take the court against their archrivals, the Big Green of Dartmouth College. GO RED!

One-eyed, one-horned, flying purple veggie eater

Big Fruits and Vegetables is at it again. You notice how they’re always like “Oh, vegetables are good for your health,” and “Eating fruits every day makes you live longer,” but come on. It’s a marketing ploy, leading us astray from our personal savior, McDonald’s.

PxHere

Just look at this latest bit of research: According to researchers from Finland, eating purple vegetables can protect against diabetes. Considering nearly 40 million Americans have diabetes (and nearly 100 million have prediabetes), anything to reduce the incidence of diabetes (people with diabetes account for one-fourth of every dollar spent in U.S. health care) would be beneficial. So, let’s humor the fruits and veggies people this time and hear them out.

It all comes down to a chemical called anthocyanin, which is a pigment that gives fruits and vegetables such as blueberries, radishes, and red cabbages their purplish color. Anthocyanin also has probiotic and anti-inflammatory effects, meaning it can help improve intestinal lining health and regulate glucose and lipid metabolic pathways. Obviously, good things if you want to avoid diabetes.

The investigators also found that, while standard anthocyanin was beneficial, acylated anthocyanin (which has an acyl group added to the sugar molecules of anthocyanin) is really what you want to go for. The acylated version, found in abundance in purple potatoes, purple carrots, radishes, and red cabbages, is tougher to digest, but the positive effects it has in the body are enhanced over the standard version.

Now, this all a compelling bit of research, but at the end of the day, you’re still eating fruits and vegetables, and we are red-blooded Americans here. We don’t do healthy foods. Although, if you were to dye our burgers with anthocyanin and make them purple, you’d have our attention. Purple is our favorite color.
 

Manuka honey better as building material than antibiotic

Milk, according to the old saying, builds strong bones, but when it comes to patients with bone loss caused by various medical reasons, researchers found that manuka honey, produced only in New Zealand and some parts of Australia, may also do the job. They soaked collagen scaffolds used for bone implants in various concentrations of the honey and found that 5% led to higher mineral formation and osteoprotegerin production, which suggests increased bone production.

Marley Dewey

But, and this is a pretty big one, the other half of the study – testing manuka honey’s ability to ward off bacteria – wasn’t so successful. Bone implants, apparently, count for almost half of all hospital-acquired infections, which obviously can put a damper on the healing process. The hope was that a biomaterial would be more effective than something like metal in lessening bacteria formation. Nope.

When the researchers soaked paper disks in honey and added them to cultures of Pseudomonas aeruginosa and Staphylococcus aureus, none of the various concentrations stopped bacterial growth in the scaffolding, even when they added antibiotics.

The sticky conclusion, you could say, is more bitter than sweet.
 

It may sound like Korn, but can it play ‘Freak on a Leash’?

Like all right-thinking Americans, we love corn, corn-based products, and almost corn. Corn on the cob grilled in the husk? Mmm. Plus, we’re big fans of the band Korn. Also, we once had a reporter here named Tim Kirn. And don’t even get us started with Karn. Best Family Feud host ever.

Quorn

But what about Quorn? Oh sure, the fungi-based meat alternative is full of yummy mycoprotein, but can it prevent colorectal cancer? Can we add Quorn to our favorites list? Let’s see what Science has to say.

Researchers at Northumbria University in Newcastle upon Tyne, England, fed a group of 20 men some meat (240 g/day) for 2 weeks – hopefully, they were allowed to eat some other food as well – and then gave them the same amount of Quorn, excuse us, fungi-derived mycoprotein equivalents, for 2 more weeks, with a 4-week washout period in between.

Levels of cancer-causing chemicals known as genotoxins fell significantly in the mycoprotein phase but rose during the meat phase. The mycoprotein diet also improved gut health “by increasing the abundance of protective bacteria such as Lactobacilli, Roseburia, and Akkermansia, which are associated with offering protection against chemically induced tumours, inflammation and bowel cancer,” they said in a statement from the university.

The meat phase, on the other hand, resulted in an increase in “gut bacteria linked with issues such as cancer, cardiovascular diseases, weight gain and other negative health outcomes,” they noted.

Science, then, seems to approve of Quorn, and that’s good enough for us. We’re adding Quorn to our diet, starting with a fungi-derived mycoproteinburger tonight while we’re watching the Cornell Big Red take the court against their archrivals, the Big Green of Dartmouth College. GO RED!

One-eyed, one-horned, flying purple veggie eater

Big Fruits and Vegetables is at it again. You notice how they’re always like “Oh, vegetables are good for your health,” and “Eating fruits every day makes you live longer,” but come on. It’s a marketing ploy, leading us astray from our personal savior, McDonald’s.

PxHere

Just look at this latest bit of research: According to researchers from Finland, eating purple vegetables can protect against diabetes. Considering nearly 40 million Americans have diabetes (and nearly 100 million have prediabetes), anything to reduce the incidence of diabetes (people with diabetes account for one-fourth of every dollar spent in U.S. health care) would be beneficial. So, let’s humor the fruits and veggies people this time and hear them out.

It all comes down to a chemical called anthocyanin, which is a pigment that gives fruits and vegetables such as blueberries, radishes, and red cabbages their purplish color. Anthocyanin also has probiotic and anti-inflammatory effects, meaning it can help improve intestinal lining health and regulate glucose and lipid metabolic pathways. Obviously, good things if you want to avoid diabetes.

The investigators also found that, while standard anthocyanin was beneficial, acylated anthocyanin (which has an acyl group added to the sugar molecules of anthocyanin) is really what you want to go for. The acylated version, found in abundance in purple potatoes, purple carrots, radishes, and red cabbages, is tougher to digest, but the positive effects it has in the body are enhanced over the standard version.

Now, this all a compelling bit of research, but at the end of the day, you’re still eating fruits and vegetables, and we are red-blooded Americans here. We don’t do healthy foods. Although, if you were to dye our burgers with anthocyanin and make them purple, you’d have our attention. Purple is our favorite color.
 

Manuka honey better as building material than antibiotic

Milk, according to the old saying, builds strong bones, but when it comes to patients with bone loss caused by various medical reasons, researchers found that manuka honey, produced only in New Zealand and some parts of Australia, may also do the job. They soaked collagen scaffolds used for bone implants in various concentrations of the honey and found that 5% led to higher mineral formation and osteoprotegerin production, which suggests increased bone production.

Marley Dewey

But, and this is a pretty big one, the other half of the study – testing manuka honey’s ability to ward off bacteria – wasn’t so successful. Bone implants, apparently, count for almost half of all hospital-acquired infections, which obviously can put a damper on the healing process. The hope was that a biomaterial would be more effective than something like metal in lessening bacteria formation. Nope.

When the researchers soaked paper disks in honey and added them to cultures of Pseudomonas aeruginosa and Staphylococcus aureus, none of the various concentrations stopped bacterial growth in the scaffolding, even when they added antibiotics.

The sticky conclusion, you could say, is more bitter than sweet.
 

It may sound like Korn, but can it play ‘Freak on a Leash’?

Like all right-thinking Americans, we love corn, corn-based products, and almost corn. Corn on the cob grilled in the husk? Mmm. Plus, we’re big fans of the band Korn. Also, we once had a reporter here named Tim Kirn. And don’t even get us started with Karn. Best Family Feud host ever.

Quorn

But what about Quorn? Oh sure, the fungi-based meat alternative is full of yummy mycoprotein, but can it prevent colorectal cancer? Can we add Quorn to our favorites list? Let’s see what Science has to say.

Researchers at Northumbria University in Newcastle upon Tyne, England, fed a group of 20 men some meat (240 g/day) for 2 weeks – hopefully, they were allowed to eat some other food as well – and then gave them the same amount of Quorn, excuse us, fungi-derived mycoprotein equivalents, for 2 more weeks, with a 4-week washout period in between.

Levels of cancer-causing chemicals known as genotoxins fell significantly in the mycoprotein phase but rose during the meat phase. The mycoprotein diet also improved gut health “by increasing the abundance of protective bacteria such as Lactobacilli, Roseburia, and Akkermansia, which are associated with offering protection against chemically induced tumours, inflammation and bowel cancer,” they said in a statement from the university.

The meat phase, on the other hand, resulted in an increase in “gut bacteria linked with issues such as cancer, cardiovascular diseases, weight gain and other negative health outcomes,” they noted.

Science, then, seems to approve of Quorn, and that’s good enough for us. We’re adding Quorn to our diet, starting with a fungi-derived mycoproteinburger tonight while we’re watching the Cornell Big Red take the court against their archrivals, the Big Green of Dartmouth College. GO RED!

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Mindi Rosen met Seuli Brill, MD, at just the right time. 

Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.

Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.  

“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”

The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.

Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus  on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.

The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.

The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.

“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.

Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.

The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition. 

Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold. 

Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care. 

“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”

Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.

In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.

In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar. 

Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.

“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”

Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.

Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.

Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.

“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”

One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.

The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.

Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.

“There are logistical challenges to even doing this that makes it less common,” she said.

Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar. 

“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.

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

Mindi Rosen met Seuli Brill, MD, at just the right time. 

Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.

Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.  

“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”

The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.

Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus  on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.

The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.

The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.

“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.

Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.

The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition. 

Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold. 

Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care. 

“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”

Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.

In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.

In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar. 

Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.

“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”

Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.

Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.

Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.

“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”

One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.

The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.

Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.

“There are logistical challenges to even doing this that makes it less common,” she said.

Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar. 

“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.

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

Mindi Rosen met Seuli Brill, MD, at just the right time. 

Ms. Rosen’s firstborn son was in the neointensive natal unit at The Ohio State University Wexner Medical Center in Columbus, and she didn’t have a pediatrician picked out yet for the baby. Nor did she have a primary care physician who could help her manage the gestational diabetes she developed during her pregnancy.

Dr. Brill, a clinical associate professor of internal medicine and pediatrics at Ohio State, suggested Ms. Rosen visit her at the new clinic she was piloting in Columbus. There, she provided pediatric care for newborns and primary care for mothers who had developed gestational diabetes.  

“I looked at my husband, my husband looked at me, and I said: ‘Why not?’ “ Ms. Rosen, 38, recalled of that 2019 meeting. “I’m so glad she walked in at that moment.”

The mother of two is still part of the rapidly growing program at the medical facility that provides care for more than 200 mothers and babies.

Launched in 2018, the clinic – called the Multi-Modal Maternal Infant Perinatal Outpatient Delivery System, or “Momi Pods,” started with a focus  on helping women with gestational diabetes, which occurs in up to 10% of pregnancies.

The program allows moms to book regular checkups for their baby, and then a follow-up appointment immediately after for themselves. Women are seen for the first 1,000 days (just under 3 years) after giving birth.

The idea was simple. Dr. Brill wanted to develop a more formalized program for the work she was already doing as a primary care physician and pediatrician. At the time, she was fielding referrals from specialists for young women who didn’t have a physician. She’d often develop a relationship with the patient over the years, go on to help oversee their care during pregnancy, then new mothers would select her as their newborn’s pediatrician.

“I would have a relationship with the mom when they did have the newborn, and then I would see the baby because I’m a pediatrician,” Dr. Brill said.

Dr. Brill was serving on the Ohio Gestational Diabetes Mellitus Collaborative, a state-backed program that aims to raise awareness about the condition and encourage more preventative care for patients. She presented her proposal to launch the program to the Ohio Department of Medicaid, which helped to fund the pilot.

The idea, she hoped, would improve postpartum follow-up care for mothers diagnosed with the condition. 

Follow-up care is especially important for women who develop gestational diabetes because the condition raises their lifetime risk of developing type 2 diabetes up to 10-fold. 

Yet most of those mothers don’t get the appropriate follow-up care during the crucial postpartum period, said Maya Subbalakshmi Venkataramani, MD, MPH, an assistant professor of medicine at Johns Hopkins University in Baltimore, who has researched parental care. 

“Things get very busy after you have a child. There’s just the general logistics of a mom having to take care of a newborn and thinking about themselves,” Dr. Venkataramani, a primary care clinician and pediatrician, said. “A lot of parents in general may not put a lot of emphasis on their own health.”

Seeking care may be especially difficult for low-income mothers who might not have consistent health care coverage, she added.

In fact, only half of women who developed gestational diabetes received primary follow-up care, according to a study published in JAMA Network Open. The study, which examined more than 280,000 insurance claims between 2015 and 2018, found only 36% of women with gestational diabetes received the recommended blood glucose testing in the first 12 weeks of the postpartum period.

In the Momi Pods program, Dr. Brill checked in on Ms. Rosen’s gestational diabetes regularly during pediatric office visits for her newborn’s care. Ms. Rosen said whenever she brought her baby in for a visit during the postpartum period, Dr. Brill measured her blood sugar. 

Dr. Brill and her team also asked how Ms. Rosen was doing physically and mentally during each visit. The screenings helped to catch a bout of postpartum depression Ms. Rosen experienced after the birth of her first son.

“I thought it was great, because honestly as a new mom I wouldn’t have followed up with myself so much,” Ms. Rosen said. “Every time you went into the doctor appointments, they’d ask you how you are doing. As a new mom, it’s so much easier to do it at the same time.”

Those who participate in the program are also more likely to complete postpartum visits with their ob.gyn. (95% vs. 58%, respectively; P < .001) than those who don’t participate, according to research Dr. Brill and colleagues published.

Dr. Brill began expanding the program’s reach nearly 2 years after its launch, targeting the services for women who are at risk for poor postpartum outcomes, including those with a history of depression, preterm labor, diabetes and congenital heart disease. Ob.gyns. in Ohio State’s network can refer their patients to the program, which now has 43 doctors trained to provide primary and pediatric care through Momi Pods. Soon-to-be moms can be referred to the program as early as the second trimester, Dr. Brill said.

Many of the mothers referred to the program don’t have a primary care clinician when they talk to Paola Beamon, RN, at Ohio State. Ms. Beamon reaches out to each referred patient over voicemail, a MyChart message, and even regular mail in hopes of helping them navigate the postpartum period. She also provides education on what a primary care clinician can offer new moms.

“Really, we’re pursuing these moms and doing everything we can so there’s less of a burden for them,” Ms. Beamon said. “A lot of them don’t even know what a primary care office does.”

One of the biggest perks to the program for new moms is that they don’t have to spend time and money traveling to a different doctor’s office, take time off work, or secure childcare in order to schedule a separate appointment for themselves, she said.

The program, which receives funding from the university and the state, even helps women get bus passes to a doctor’s appointment if needed.

Dyad programs targeting women with substance abuse disorders or mental health conditions have existed for many years. But catering to women with gestational diabetes or other medical conditions appears to be new. In part, Dr. Venkataramani said, because scheduling and space can be big hurdles to launch such a program, as well as finding doctors who can care for both baby and mother.

“There are logistical challenges to even doing this that makes it less common,” she said.

Dr. Brill said she is not aware of any other programs that are structured like the tandem care clinic at Ohio State. She hopes, however, that the program can be a model for other hospital systems to consider, and she is working to expand the program regionally. Her team is collecting data – including on the best way to schedule patients – to help other clinics develop something similar. 

“We really want to leverage that expertise to make it easier for moms to get care with their infants and remove barriers to care,” she said.

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

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

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

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

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

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

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