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Low-dose aspirin cuts type 2 diabetes risk in over-65s
The data come from a secondary analysis of ASPREE, a double-blind, placebo-controlled trial of healthy adults aged 65 years or older, showing that 100 mg of aspirin taken daily for about 5 years did not provide a cardiovascular benefit but did significantly raise the risk for bleeding.
This new analysis shows that individuals taking aspirin had a 15% lower risk for developing type 2 diabetes and that the medication slowed the rate of increase in fasting plasma glucose, compared with placebo, during follow-up.
However, lead author Sophia Zoungas, MBBS, PhD, head of the School of Public Health and Preventive Medicine, Monash University, Melbourne, said: “Major prescribing guidelines now recommend older adults take daily aspirin only when there is a medical reason to do so, such as after a heart attack. ... Although these new findings are of interest, they do not change the clinical advice about aspirin use in older people at this time.”
Nonetheless, she said in an interview, “at this time, our findings are exploratory but ignite the debate of the important role that anti-inflammatory approaches may play in preventing diabetes. Further work is currently underway to understand which subpopulations may be better targeted and to understand the balance of risk versus benefit.”
The results are scheduled to be presented at the upcoming meeting of the European Association for the Study of Diabetes, taking place Oct. 2-6 in Hamburg, Germany.
New findings not robust enough to change current practice
Asked to comment, Debabrata Mukherjee, MD, said: “Given the post hoc secondary nature of the analysis, the findings should be considered hypothesis generating and not definitive… At this time, based on prospective randomized studies, the risks of aspirin outweigh the benefits for aspirin in older adults.”
Among those studies was an ASPREE substudy showing failure of low-dose aspirin to reduce fracture risk while increasing the risk for serious falls, and two other trials, ARRIVE and ASCEND, also showing that harms of aspirin outweigh the benefits in people with cardiovascular risk but not diabetes, and in those with diabetes, respectively, said Dr. Mukherjee, professor and chair of the department of internal medicine at Texas Tech University Health Sciences Center at El Paso.
And, Mukherjee noted, in 2019 the American College of Cardiology updated its practice guidelines to say that low-dose aspirin should not be administered on a routine basis for the primary prevention of atherosclerotic cardiovascular disease in adults over age 70. In 2021, the American Diabetes Association seconded that recommendation.
Asked whether these newest findings might change current practice for any higher-risk subgroup, such as people with prediabetes, Dr. Mukherjee replied: “Unless there is a prospective randomized trial that validates these findings in those with prediabetes, the findings should not change practice. There are also no data [showing] that another antiplatelet agent would be indicated or would be beneficial. Instead, I would recommend lifestyle changes including regular exercise and a healthy diet to minimize risk of diabetes.”
The 16,209 ASPREE participants were community dwelling and did not have diabetes, cardiovascular disease, or dementia at baseline. They were randomized in a 1:1 ratio to receive 100 mg/d of enteric-coated aspirin or placebo. Over a median follow-up of 4.7 years, the proportions developing type 2 diabetes were 5.7% with aspirin versus 6.6% with placebo (hazard ratio, 0.85; P = .01).
The annual rate of increase in fasting plasma glucose over the follow-up period was slowed by 0.006 mmol/L with aspirin, compared with placebo, also a significant difference (P = .004).
According to Dr. Zoungas, “the potential for anti-inflammatory agents like aspirin to prevent type 2 diabetes or improve glucose levels needs further study.”
The ASPREE trial was supported by the U.S. National Institutes of Health, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Dr. Zoungas and Dr. Mukherjee have no disclosures.
A version of this article first appeared on Medscape.com.
The data come from a secondary analysis of ASPREE, a double-blind, placebo-controlled trial of healthy adults aged 65 years or older, showing that 100 mg of aspirin taken daily for about 5 years did not provide a cardiovascular benefit but did significantly raise the risk for bleeding.
This new analysis shows that individuals taking aspirin had a 15% lower risk for developing type 2 diabetes and that the medication slowed the rate of increase in fasting plasma glucose, compared with placebo, during follow-up.
However, lead author Sophia Zoungas, MBBS, PhD, head of the School of Public Health and Preventive Medicine, Monash University, Melbourne, said: “Major prescribing guidelines now recommend older adults take daily aspirin only when there is a medical reason to do so, such as after a heart attack. ... Although these new findings are of interest, they do not change the clinical advice about aspirin use in older people at this time.”
Nonetheless, she said in an interview, “at this time, our findings are exploratory but ignite the debate of the important role that anti-inflammatory approaches may play in preventing diabetes. Further work is currently underway to understand which subpopulations may be better targeted and to understand the balance of risk versus benefit.”
The results are scheduled to be presented at the upcoming meeting of the European Association for the Study of Diabetes, taking place Oct. 2-6 in Hamburg, Germany.
New findings not robust enough to change current practice
Asked to comment, Debabrata Mukherjee, MD, said: “Given the post hoc secondary nature of the analysis, the findings should be considered hypothesis generating and not definitive… At this time, based on prospective randomized studies, the risks of aspirin outweigh the benefits for aspirin in older adults.”
Among those studies was an ASPREE substudy showing failure of low-dose aspirin to reduce fracture risk while increasing the risk for serious falls, and two other trials, ARRIVE and ASCEND, also showing that harms of aspirin outweigh the benefits in people with cardiovascular risk but not diabetes, and in those with diabetes, respectively, said Dr. Mukherjee, professor and chair of the department of internal medicine at Texas Tech University Health Sciences Center at El Paso.
And, Mukherjee noted, in 2019 the American College of Cardiology updated its practice guidelines to say that low-dose aspirin should not be administered on a routine basis for the primary prevention of atherosclerotic cardiovascular disease in adults over age 70. In 2021, the American Diabetes Association seconded that recommendation.
Asked whether these newest findings might change current practice for any higher-risk subgroup, such as people with prediabetes, Dr. Mukherjee replied: “Unless there is a prospective randomized trial that validates these findings in those with prediabetes, the findings should not change practice. There are also no data [showing] that another antiplatelet agent would be indicated or would be beneficial. Instead, I would recommend lifestyle changes including regular exercise and a healthy diet to minimize risk of diabetes.”
The 16,209 ASPREE participants were community dwelling and did not have diabetes, cardiovascular disease, or dementia at baseline. They were randomized in a 1:1 ratio to receive 100 mg/d of enteric-coated aspirin or placebo. Over a median follow-up of 4.7 years, the proportions developing type 2 diabetes were 5.7% with aspirin versus 6.6% with placebo (hazard ratio, 0.85; P = .01).
The annual rate of increase in fasting plasma glucose over the follow-up period was slowed by 0.006 mmol/L with aspirin, compared with placebo, also a significant difference (P = .004).
According to Dr. Zoungas, “the potential for anti-inflammatory agents like aspirin to prevent type 2 diabetes or improve glucose levels needs further study.”
The ASPREE trial was supported by the U.S. National Institutes of Health, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Dr. Zoungas and Dr. Mukherjee have no disclosures.
A version of this article first appeared on Medscape.com.
The data come from a secondary analysis of ASPREE, a double-blind, placebo-controlled trial of healthy adults aged 65 years or older, showing that 100 mg of aspirin taken daily for about 5 years did not provide a cardiovascular benefit but did significantly raise the risk for bleeding.
This new analysis shows that individuals taking aspirin had a 15% lower risk for developing type 2 diabetes and that the medication slowed the rate of increase in fasting plasma glucose, compared with placebo, during follow-up.
However, lead author Sophia Zoungas, MBBS, PhD, head of the School of Public Health and Preventive Medicine, Monash University, Melbourne, said: “Major prescribing guidelines now recommend older adults take daily aspirin only when there is a medical reason to do so, such as after a heart attack. ... Although these new findings are of interest, they do not change the clinical advice about aspirin use in older people at this time.”
Nonetheless, she said in an interview, “at this time, our findings are exploratory but ignite the debate of the important role that anti-inflammatory approaches may play in preventing diabetes. Further work is currently underway to understand which subpopulations may be better targeted and to understand the balance of risk versus benefit.”
The results are scheduled to be presented at the upcoming meeting of the European Association for the Study of Diabetes, taking place Oct. 2-6 in Hamburg, Germany.
New findings not robust enough to change current practice
Asked to comment, Debabrata Mukherjee, MD, said: “Given the post hoc secondary nature of the analysis, the findings should be considered hypothesis generating and not definitive… At this time, based on prospective randomized studies, the risks of aspirin outweigh the benefits for aspirin in older adults.”
Among those studies was an ASPREE substudy showing failure of low-dose aspirin to reduce fracture risk while increasing the risk for serious falls, and two other trials, ARRIVE and ASCEND, also showing that harms of aspirin outweigh the benefits in people with cardiovascular risk but not diabetes, and in those with diabetes, respectively, said Dr. Mukherjee, professor and chair of the department of internal medicine at Texas Tech University Health Sciences Center at El Paso.
And, Mukherjee noted, in 2019 the American College of Cardiology updated its practice guidelines to say that low-dose aspirin should not be administered on a routine basis for the primary prevention of atherosclerotic cardiovascular disease in adults over age 70. In 2021, the American Diabetes Association seconded that recommendation.
Asked whether these newest findings might change current practice for any higher-risk subgroup, such as people with prediabetes, Dr. Mukherjee replied: “Unless there is a prospective randomized trial that validates these findings in those with prediabetes, the findings should not change practice. There are also no data [showing] that another antiplatelet agent would be indicated or would be beneficial. Instead, I would recommend lifestyle changes including regular exercise and a healthy diet to minimize risk of diabetes.”
The 16,209 ASPREE participants were community dwelling and did not have diabetes, cardiovascular disease, or dementia at baseline. They were randomized in a 1:1 ratio to receive 100 mg/d of enteric-coated aspirin or placebo. Over a median follow-up of 4.7 years, the proportions developing type 2 diabetes were 5.7% with aspirin versus 6.6% with placebo (hazard ratio, 0.85; P = .01).
The annual rate of increase in fasting plasma glucose over the follow-up period was slowed by 0.006 mmol/L with aspirin, compared with placebo, also a significant difference (P = .004).
According to Dr. Zoungas, “the potential for anti-inflammatory agents like aspirin to prevent type 2 diabetes or improve glucose levels needs further study.”
The ASPREE trial was supported by the U.S. National Institutes of Health, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Dr. Zoungas and Dr. Mukherjee have no disclosures.
A version of this article first appeared on Medscape.com.
FROM EASD 2023
Experts debate low-carb diets for people with diabetes
It’s an ongoing debate in the diabetes world: Is it ideal to consume a very-low-carbohydrate diet, or is it better to go with moderate amounts of healthful carbs?
At the annual scientific sessions of the American Diabetes Association, Carol F. Kirkpatrick, PhD, RDN, spoke first, arguing in favor of diets consisting of moderate, high-quality carbohydrates.
Dina Hafez Griauzde, MD, countered that very-low-carbohydrate diets are more beneficial for people with diabetes, primarily type 2 diabetes.
Both speakers based their arguments on published evidence but agreed in the end that discussion with patients about individual dietary preferences should play a major role in the ultimate decision.
Moderate-carbohydrate eating is best
Dr. Kirkpatrick began by explaining that definitions of “low carb” vary in the literature, which makes comparisons between studies difficult. On the basis of a 2019 review that she coauthored, “moderate” carbohydrate consumption was defined as a diet in which 26%-44% of total daily calories are from carbohydrates. “Low” carbohydrate consumption was defined as a diet in which 10%-25% of calories were from carbohydrates. Consuming less than 10% was defined as a very-low-carbohydrate diet (i.e., a ketogenic diet).
Across studies, she noted, the literature shows that within the first 6 months weight loss is typically greater with carbohydrate-restricted diets than with higher-carbohydrate diets, but that by 1 year and beyond weight loss is similar.
“That can be partly due to the difficulty in people maintaining that very severe dietary restriction, although ... we can all acknowledge that it’s difficult for patients to adhere to any dietary pattern, so for sure by 12 months, the difference in the weight loss is gone between the two,” said Dr. Kirkpatrick, of Midwest Biomedical Research, Pocatello, Idaho.
In a recent meta-analysis of 35 trials that examined the dose-dependent effects of carbohydrate restriction for patients with type 2 diabetes, there was a significant decrease in weight as carbohydrates were reduced. But by 12 months (17 trials), the greatest weight reduction was seen at 35% carbohydrate intake.
“It may just be that people were able to adhere to that moderate intake better,” she explained.
Regarding lipids, in her 2019 review and in several meta-analyses since, the effects on low-density lipoprotein cholesterol (LDL-C) varied. For some patients, adhering to a low-carb diet led to reductions in LDL-C, especially if the participants also lost weight, whereas in other patients, a low-carb diet led to an increase in LDL-C.
Either way, a high intake of saturated fatty acids is key to an increase in LDL-C, Dr. Kirkpatrick noted. “So, it’s important that, if a patient chooses to follow a very low carbohydrate diet or any kind of dietary pattern that restricts carbohydrate, that they replace the carbohydrate with unsaturated fat and not saturated fatty acid foods to avoid that increase in LDL-C.”
Generally, the evidence also shows that carbohydrate restriction typically leads to lower triglyceride levels and higher high-density lipoprotein (HDL) cholesterol levels. However, the same meta-analysis showed that the greatest reduction in LDL-C occurred at about 40% carbohydrate consumption.
Another recent meta-analysis showed that LDL-C rose significantly by an average 12.4 mg/dL with very-low-carb (3%-30%) diets, but only slightly, by 0.4 mg/dL, with moderate carb (40%-45%) intake.
Consuming very-low-carb diets did lead to greater reductions in triglycerides, compared with consuming moderate carb diets (23.9 mg/dL vs. 8.9 mg/dL).
“However, in terms of cardiovascular health, we are not entirely sure what that means. ... We have to look at the overall results in the presence of both triglyceride lowering as well as LDL cholesterol,” Dr. Kirkpatrick noted.
Carbohydrate restriction did consistently lead to lower hemoglobin A1c levels by an average of 0.4, 0.6, and 1.0 percentage points at 6 months for diets of 40%, 30%, and 15% carbohydrate, respectively. However, by 12 months, the effect had waned to 0.15, 0.2, and 0.4 A1c percentage points.
“Again, carbohydrate restriction, especially severe, is difficult for people to adhere to, and moderate carbohydrate intake would allow our patients to consume an appropriate amount of carbohydrate and still achieve improved glycemic control,” Dr. Kirkpatrick said.
Two large randomized controlled trials – PREDIMED and CORDIOPREV – examined the effects of the Mediterranean diet on cardiovascular disease prevention. Both showed a decrease in cardiovascular events with the Mediterranean diet, which involves consuming moderate amounts of carbohydrates.
“The Mediterranean dietary pattern has the strongest evidence for benefit, and it’s moderate in carbohydrates,” she concluded.
Very-low-carbohydrate eating is best
Dr. Griauzde was a last-minute replacement speaker for William S. Yancy Jr, MD, of Duke University, Durham, N.C., and presented his slides. She argued that consuming a very low carb diet improves glycemia and that it does not increase but possibly lowers cardiovascular risk.
She began by noting that prior to the discovery of insulin very-low-carb diets had been consumed for over a century to prolong life for people with type 1 diabetes.
“We have long recognized the deleterious role of carbohydrate in type 1 diabetes management, and we have increasingly recognized that role in the management of type 2 diabetes,” said Dr. Griauzde of the University of Michigan in Ann Arbor.
In a small study that compared maintaining a very-low-carb diet for 2 weeks with maintaining a high-carb diet for 2 weeks, total glucose areas under the curve were substantially lower (P < .05) during the low-carb phase, while A1c levels dropped from 7.3% to 6.8% (P = .006).
“We don’t see those outcomes with meds,” Dr. Griauzde noted, adding, “A diet very low in carbohydrates is one of the most potent tools we have to help our patients achieve glycemic control.”
Dr. Griauzde said that the carbohydrate-insulin model provides an explanation for why dietary carbohydrates are particularly obesogenic and metabolically harmful. That model contrasts with the energy balance model, which suggests that all calories are equal.
The rationale of the carbohydrate-insulin model is that dietary carbohydrate – either sugar or starch – raises serum glucose and insulin levels. A carbohydrate-restricted diet therefore reduces the dietary contribution to serum glucose, which then results in lower insulin levels. Insulin is a potent stimulator of lipogenesis (fat storage), and it is a potent inhibitor of lipolysis (the burning of fat). By lowering insulin levels, stored body fat is burned, serum ketone levels increase, and body weight is lowered.
This model suggests that, when insulin levels are chronically high because of excess carbohydrate consumption, circulating fuels are lowered, which leads to an increase in hunger and to overeating. This was demonstrated in a study that compared different levels of isocaloric glycemic index diets in 12 teenage boys with overweight or obesity. The higher-carbohydrate meals led to higher glucose and insulin levels and more food consumption.
In a systematic review of 13 trials of restricted-carbohydrate diets (< 45% carbohydrates) for adults with diabetes, the degree of improvement in A1c level correlated with the degree of carbohydrate restriction over 2-26 weeks (P = .013).
And in a network meta-analysis of 56 trials that compared nine diets among a total of 4,937 participants with type 2 diabetes, one conclusion was that “for reducing A1c, the low-carbohydrate diet was ranked as the best dietary approach (SUCRA: 84%), followed by the Mediterranean diet (80%), and Paleolithic diet (76%), compared with a control diet.”
Regarding the criticism that very-low-carbohydrate diets are high in saturated fat and therefore raise the risk of cardiovascular disease, Dr. Griauzde pointed to another meta-analysis of 21 prospective studies with more than 300,000 participants with 5-25 years of follow-up. In that analysis, the intake of saturated fat was not associated with an increased risk of cardiovascular disease or stroke.
Furthermore, a 12-week randomized controlled trial that involved 40 adults with overweight also suggested that a very-low-carb diet may be superior to a low-fat diet in improving aspects of the metabolic syndrome, including body mass index, lipid levels, and insulin sensitivity. Small LDL particles, which are more atherogenic than larger LDL particles, also decreased despite a threefold increase in saturated fat intake.
Rebuttals: Overall diet, patient preference matter
During the rebuttals, Dr. Kirkpatrick pointed out that large LDL particles are also atherogenic. In addition, she noted that the studies that showed that saturated fat isn’t associated with cardiovascular disease didn’t consider the macronutrients that replaced the saturated fat.
“It really is about increasing consumption of foods that we know are associated with cardiovascular benefit, including plant-based foods that are high quality and not refined carbohydrates ... and healthy protein sources. ... Hopefully we can step away from just looking at macronutrients and look at the total amount of food that people are choosing to eat.”
Importantly, Dr. Kirkpatrick said, patients need to be asked about their current dietary patterns and preferences. “Interventions should be patient centered and sensitive to cultural differences. Personalized lifestyle interventions increase the likelihood of success.”
Dr. Griauzde pointed out that newer antiobesity drugs can be added to any diet to decrease appetite and enhance adherence.
Dr. Griauzde also observed, “We can label a very-low-carbohydrate diet ‘extreme,’ but maybe, from the patient’s perspective, it’s extreme to take 200 units of insulin a day. If you can give them the opportunity to discontinue use of the insulin by following a very-low-carbohydrate dietary pattern, that is the opportunity that our patients deserve to have.”
But overall, she agreed with Dr. Kirkpatrick about individualizing any dietary approach: “We will never know from any of the trials that have been done or that will be done in the future what diet is best for an individual patient. ... Our job is to help our patients find the dietary approach that works best for them.”
Dr. Kirkpatrick is a clinical scientist with Midwest Biomedical Research, which has received funding from various food and pharmaceutical companies. She has not received any direct funding. Dr. Yancy is a consultant for The Simply Good Foods Co. Dr. Griauzde has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It’s an ongoing debate in the diabetes world: Is it ideal to consume a very-low-carbohydrate diet, or is it better to go with moderate amounts of healthful carbs?
At the annual scientific sessions of the American Diabetes Association, Carol F. Kirkpatrick, PhD, RDN, spoke first, arguing in favor of diets consisting of moderate, high-quality carbohydrates.
Dina Hafez Griauzde, MD, countered that very-low-carbohydrate diets are more beneficial for people with diabetes, primarily type 2 diabetes.
Both speakers based their arguments on published evidence but agreed in the end that discussion with patients about individual dietary preferences should play a major role in the ultimate decision.
Moderate-carbohydrate eating is best
Dr. Kirkpatrick began by explaining that definitions of “low carb” vary in the literature, which makes comparisons between studies difficult. On the basis of a 2019 review that she coauthored, “moderate” carbohydrate consumption was defined as a diet in which 26%-44% of total daily calories are from carbohydrates. “Low” carbohydrate consumption was defined as a diet in which 10%-25% of calories were from carbohydrates. Consuming less than 10% was defined as a very-low-carbohydrate diet (i.e., a ketogenic diet).
Across studies, she noted, the literature shows that within the first 6 months weight loss is typically greater with carbohydrate-restricted diets than with higher-carbohydrate diets, but that by 1 year and beyond weight loss is similar.
“That can be partly due to the difficulty in people maintaining that very severe dietary restriction, although ... we can all acknowledge that it’s difficult for patients to adhere to any dietary pattern, so for sure by 12 months, the difference in the weight loss is gone between the two,” said Dr. Kirkpatrick, of Midwest Biomedical Research, Pocatello, Idaho.
In a recent meta-analysis of 35 trials that examined the dose-dependent effects of carbohydrate restriction for patients with type 2 diabetes, there was a significant decrease in weight as carbohydrates were reduced. But by 12 months (17 trials), the greatest weight reduction was seen at 35% carbohydrate intake.
“It may just be that people were able to adhere to that moderate intake better,” she explained.
Regarding lipids, in her 2019 review and in several meta-analyses since, the effects on low-density lipoprotein cholesterol (LDL-C) varied. For some patients, adhering to a low-carb diet led to reductions in LDL-C, especially if the participants also lost weight, whereas in other patients, a low-carb diet led to an increase in LDL-C.
Either way, a high intake of saturated fatty acids is key to an increase in LDL-C, Dr. Kirkpatrick noted. “So, it’s important that, if a patient chooses to follow a very low carbohydrate diet or any kind of dietary pattern that restricts carbohydrate, that they replace the carbohydrate with unsaturated fat and not saturated fatty acid foods to avoid that increase in LDL-C.”
Generally, the evidence also shows that carbohydrate restriction typically leads to lower triglyceride levels and higher high-density lipoprotein (HDL) cholesterol levels. However, the same meta-analysis showed that the greatest reduction in LDL-C occurred at about 40% carbohydrate consumption.
Another recent meta-analysis showed that LDL-C rose significantly by an average 12.4 mg/dL with very-low-carb (3%-30%) diets, but only slightly, by 0.4 mg/dL, with moderate carb (40%-45%) intake.
Consuming very-low-carb diets did lead to greater reductions in triglycerides, compared with consuming moderate carb diets (23.9 mg/dL vs. 8.9 mg/dL).
“However, in terms of cardiovascular health, we are not entirely sure what that means. ... We have to look at the overall results in the presence of both triglyceride lowering as well as LDL cholesterol,” Dr. Kirkpatrick noted.
Carbohydrate restriction did consistently lead to lower hemoglobin A1c levels by an average of 0.4, 0.6, and 1.0 percentage points at 6 months for diets of 40%, 30%, and 15% carbohydrate, respectively. However, by 12 months, the effect had waned to 0.15, 0.2, and 0.4 A1c percentage points.
“Again, carbohydrate restriction, especially severe, is difficult for people to adhere to, and moderate carbohydrate intake would allow our patients to consume an appropriate amount of carbohydrate and still achieve improved glycemic control,” Dr. Kirkpatrick said.
Two large randomized controlled trials – PREDIMED and CORDIOPREV – examined the effects of the Mediterranean diet on cardiovascular disease prevention. Both showed a decrease in cardiovascular events with the Mediterranean diet, which involves consuming moderate amounts of carbohydrates.
“The Mediterranean dietary pattern has the strongest evidence for benefit, and it’s moderate in carbohydrates,” she concluded.
Very-low-carbohydrate eating is best
Dr. Griauzde was a last-minute replacement speaker for William S. Yancy Jr, MD, of Duke University, Durham, N.C., and presented his slides. She argued that consuming a very low carb diet improves glycemia and that it does not increase but possibly lowers cardiovascular risk.
She began by noting that prior to the discovery of insulin very-low-carb diets had been consumed for over a century to prolong life for people with type 1 diabetes.
“We have long recognized the deleterious role of carbohydrate in type 1 diabetes management, and we have increasingly recognized that role in the management of type 2 diabetes,” said Dr. Griauzde of the University of Michigan in Ann Arbor.
In a small study that compared maintaining a very-low-carb diet for 2 weeks with maintaining a high-carb diet for 2 weeks, total glucose areas under the curve were substantially lower (P < .05) during the low-carb phase, while A1c levels dropped from 7.3% to 6.8% (P = .006).
“We don’t see those outcomes with meds,” Dr. Griauzde noted, adding, “A diet very low in carbohydrates is one of the most potent tools we have to help our patients achieve glycemic control.”
Dr. Griauzde said that the carbohydrate-insulin model provides an explanation for why dietary carbohydrates are particularly obesogenic and metabolically harmful. That model contrasts with the energy balance model, which suggests that all calories are equal.
The rationale of the carbohydrate-insulin model is that dietary carbohydrate – either sugar or starch – raises serum glucose and insulin levels. A carbohydrate-restricted diet therefore reduces the dietary contribution to serum glucose, which then results in lower insulin levels. Insulin is a potent stimulator of lipogenesis (fat storage), and it is a potent inhibitor of lipolysis (the burning of fat). By lowering insulin levels, stored body fat is burned, serum ketone levels increase, and body weight is lowered.
This model suggests that, when insulin levels are chronically high because of excess carbohydrate consumption, circulating fuels are lowered, which leads to an increase in hunger and to overeating. This was demonstrated in a study that compared different levels of isocaloric glycemic index diets in 12 teenage boys with overweight or obesity. The higher-carbohydrate meals led to higher glucose and insulin levels and more food consumption.
In a systematic review of 13 trials of restricted-carbohydrate diets (< 45% carbohydrates) for adults with diabetes, the degree of improvement in A1c level correlated with the degree of carbohydrate restriction over 2-26 weeks (P = .013).
And in a network meta-analysis of 56 trials that compared nine diets among a total of 4,937 participants with type 2 diabetes, one conclusion was that “for reducing A1c, the low-carbohydrate diet was ranked as the best dietary approach (SUCRA: 84%), followed by the Mediterranean diet (80%), and Paleolithic diet (76%), compared with a control diet.”
Regarding the criticism that very-low-carbohydrate diets are high in saturated fat and therefore raise the risk of cardiovascular disease, Dr. Griauzde pointed to another meta-analysis of 21 prospective studies with more than 300,000 participants with 5-25 years of follow-up. In that analysis, the intake of saturated fat was not associated with an increased risk of cardiovascular disease or stroke.
Furthermore, a 12-week randomized controlled trial that involved 40 adults with overweight also suggested that a very-low-carb diet may be superior to a low-fat diet in improving aspects of the metabolic syndrome, including body mass index, lipid levels, and insulin sensitivity. Small LDL particles, which are more atherogenic than larger LDL particles, also decreased despite a threefold increase in saturated fat intake.
Rebuttals: Overall diet, patient preference matter
During the rebuttals, Dr. Kirkpatrick pointed out that large LDL particles are also atherogenic. In addition, she noted that the studies that showed that saturated fat isn’t associated with cardiovascular disease didn’t consider the macronutrients that replaced the saturated fat.
“It really is about increasing consumption of foods that we know are associated with cardiovascular benefit, including plant-based foods that are high quality and not refined carbohydrates ... and healthy protein sources. ... Hopefully we can step away from just looking at macronutrients and look at the total amount of food that people are choosing to eat.”
Importantly, Dr. Kirkpatrick said, patients need to be asked about their current dietary patterns and preferences. “Interventions should be patient centered and sensitive to cultural differences. Personalized lifestyle interventions increase the likelihood of success.”
Dr. Griauzde pointed out that newer antiobesity drugs can be added to any diet to decrease appetite and enhance adherence.
Dr. Griauzde also observed, “We can label a very-low-carbohydrate diet ‘extreme,’ but maybe, from the patient’s perspective, it’s extreme to take 200 units of insulin a day. If you can give them the opportunity to discontinue use of the insulin by following a very-low-carbohydrate dietary pattern, that is the opportunity that our patients deserve to have.”
But overall, she agreed with Dr. Kirkpatrick about individualizing any dietary approach: “We will never know from any of the trials that have been done or that will be done in the future what diet is best for an individual patient. ... Our job is to help our patients find the dietary approach that works best for them.”
Dr. Kirkpatrick is a clinical scientist with Midwest Biomedical Research, which has received funding from various food and pharmaceutical companies. She has not received any direct funding. Dr. Yancy is a consultant for The Simply Good Foods Co. Dr. Griauzde has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It’s an ongoing debate in the diabetes world: Is it ideal to consume a very-low-carbohydrate diet, or is it better to go with moderate amounts of healthful carbs?
At the annual scientific sessions of the American Diabetes Association, Carol F. Kirkpatrick, PhD, RDN, spoke first, arguing in favor of diets consisting of moderate, high-quality carbohydrates.
Dina Hafez Griauzde, MD, countered that very-low-carbohydrate diets are more beneficial for people with diabetes, primarily type 2 diabetes.
Both speakers based their arguments on published evidence but agreed in the end that discussion with patients about individual dietary preferences should play a major role in the ultimate decision.
Moderate-carbohydrate eating is best
Dr. Kirkpatrick began by explaining that definitions of “low carb” vary in the literature, which makes comparisons between studies difficult. On the basis of a 2019 review that she coauthored, “moderate” carbohydrate consumption was defined as a diet in which 26%-44% of total daily calories are from carbohydrates. “Low” carbohydrate consumption was defined as a diet in which 10%-25% of calories were from carbohydrates. Consuming less than 10% was defined as a very-low-carbohydrate diet (i.e., a ketogenic diet).
Across studies, she noted, the literature shows that within the first 6 months weight loss is typically greater with carbohydrate-restricted diets than with higher-carbohydrate diets, but that by 1 year and beyond weight loss is similar.
“That can be partly due to the difficulty in people maintaining that very severe dietary restriction, although ... we can all acknowledge that it’s difficult for patients to adhere to any dietary pattern, so for sure by 12 months, the difference in the weight loss is gone between the two,” said Dr. Kirkpatrick, of Midwest Biomedical Research, Pocatello, Idaho.
In a recent meta-analysis of 35 trials that examined the dose-dependent effects of carbohydrate restriction for patients with type 2 diabetes, there was a significant decrease in weight as carbohydrates were reduced. But by 12 months (17 trials), the greatest weight reduction was seen at 35% carbohydrate intake.
“It may just be that people were able to adhere to that moderate intake better,” she explained.
Regarding lipids, in her 2019 review and in several meta-analyses since, the effects on low-density lipoprotein cholesterol (LDL-C) varied. For some patients, adhering to a low-carb diet led to reductions in LDL-C, especially if the participants also lost weight, whereas in other patients, a low-carb diet led to an increase in LDL-C.
Either way, a high intake of saturated fatty acids is key to an increase in LDL-C, Dr. Kirkpatrick noted. “So, it’s important that, if a patient chooses to follow a very low carbohydrate diet or any kind of dietary pattern that restricts carbohydrate, that they replace the carbohydrate with unsaturated fat and not saturated fatty acid foods to avoid that increase in LDL-C.”
Generally, the evidence also shows that carbohydrate restriction typically leads to lower triglyceride levels and higher high-density lipoprotein (HDL) cholesterol levels. However, the same meta-analysis showed that the greatest reduction in LDL-C occurred at about 40% carbohydrate consumption.
Another recent meta-analysis showed that LDL-C rose significantly by an average 12.4 mg/dL with very-low-carb (3%-30%) diets, but only slightly, by 0.4 mg/dL, with moderate carb (40%-45%) intake.
Consuming very-low-carb diets did lead to greater reductions in triglycerides, compared with consuming moderate carb diets (23.9 mg/dL vs. 8.9 mg/dL).
“However, in terms of cardiovascular health, we are not entirely sure what that means. ... We have to look at the overall results in the presence of both triglyceride lowering as well as LDL cholesterol,” Dr. Kirkpatrick noted.
Carbohydrate restriction did consistently lead to lower hemoglobin A1c levels by an average of 0.4, 0.6, and 1.0 percentage points at 6 months for diets of 40%, 30%, and 15% carbohydrate, respectively. However, by 12 months, the effect had waned to 0.15, 0.2, and 0.4 A1c percentage points.
“Again, carbohydrate restriction, especially severe, is difficult for people to adhere to, and moderate carbohydrate intake would allow our patients to consume an appropriate amount of carbohydrate and still achieve improved glycemic control,” Dr. Kirkpatrick said.
Two large randomized controlled trials – PREDIMED and CORDIOPREV – examined the effects of the Mediterranean diet on cardiovascular disease prevention. Both showed a decrease in cardiovascular events with the Mediterranean diet, which involves consuming moderate amounts of carbohydrates.
“The Mediterranean dietary pattern has the strongest evidence for benefit, and it’s moderate in carbohydrates,” she concluded.
Very-low-carbohydrate eating is best
Dr. Griauzde was a last-minute replacement speaker for William S. Yancy Jr, MD, of Duke University, Durham, N.C., and presented his slides. She argued that consuming a very low carb diet improves glycemia and that it does not increase but possibly lowers cardiovascular risk.
She began by noting that prior to the discovery of insulin very-low-carb diets had been consumed for over a century to prolong life for people with type 1 diabetes.
“We have long recognized the deleterious role of carbohydrate in type 1 diabetes management, and we have increasingly recognized that role in the management of type 2 diabetes,” said Dr. Griauzde of the University of Michigan in Ann Arbor.
In a small study that compared maintaining a very-low-carb diet for 2 weeks with maintaining a high-carb diet for 2 weeks, total glucose areas under the curve were substantially lower (P < .05) during the low-carb phase, while A1c levels dropped from 7.3% to 6.8% (P = .006).
“We don’t see those outcomes with meds,” Dr. Griauzde noted, adding, “A diet very low in carbohydrates is one of the most potent tools we have to help our patients achieve glycemic control.”
Dr. Griauzde said that the carbohydrate-insulin model provides an explanation for why dietary carbohydrates are particularly obesogenic and metabolically harmful. That model contrasts with the energy balance model, which suggests that all calories are equal.
The rationale of the carbohydrate-insulin model is that dietary carbohydrate – either sugar or starch – raises serum glucose and insulin levels. A carbohydrate-restricted diet therefore reduces the dietary contribution to serum glucose, which then results in lower insulin levels. Insulin is a potent stimulator of lipogenesis (fat storage), and it is a potent inhibitor of lipolysis (the burning of fat). By lowering insulin levels, stored body fat is burned, serum ketone levels increase, and body weight is lowered.
This model suggests that, when insulin levels are chronically high because of excess carbohydrate consumption, circulating fuels are lowered, which leads to an increase in hunger and to overeating. This was demonstrated in a study that compared different levels of isocaloric glycemic index diets in 12 teenage boys with overweight or obesity. The higher-carbohydrate meals led to higher glucose and insulin levels and more food consumption.
In a systematic review of 13 trials of restricted-carbohydrate diets (< 45% carbohydrates) for adults with diabetes, the degree of improvement in A1c level correlated with the degree of carbohydrate restriction over 2-26 weeks (P = .013).
And in a network meta-analysis of 56 trials that compared nine diets among a total of 4,937 participants with type 2 diabetes, one conclusion was that “for reducing A1c, the low-carbohydrate diet was ranked as the best dietary approach (SUCRA: 84%), followed by the Mediterranean diet (80%), and Paleolithic diet (76%), compared with a control diet.”
Regarding the criticism that very-low-carbohydrate diets are high in saturated fat and therefore raise the risk of cardiovascular disease, Dr. Griauzde pointed to another meta-analysis of 21 prospective studies with more than 300,000 participants with 5-25 years of follow-up. In that analysis, the intake of saturated fat was not associated with an increased risk of cardiovascular disease or stroke.
Furthermore, a 12-week randomized controlled trial that involved 40 adults with overweight also suggested that a very-low-carb diet may be superior to a low-fat diet in improving aspects of the metabolic syndrome, including body mass index, lipid levels, and insulin sensitivity. Small LDL particles, which are more atherogenic than larger LDL particles, also decreased despite a threefold increase in saturated fat intake.
Rebuttals: Overall diet, patient preference matter
During the rebuttals, Dr. Kirkpatrick pointed out that large LDL particles are also atherogenic. In addition, she noted that the studies that showed that saturated fat isn’t associated with cardiovascular disease didn’t consider the macronutrients that replaced the saturated fat.
“It really is about increasing consumption of foods that we know are associated with cardiovascular benefit, including plant-based foods that are high quality and not refined carbohydrates ... and healthy protein sources. ... Hopefully we can step away from just looking at macronutrients and look at the total amount of food that people are choosing to eat.”
Importantly, Dr. Kirkpatrick said, patients need to be asked about their current dietary patterns and preferences. “Interventions should be patient centered and sensitive to cultural differences. Personalized lifestyle interventions increase the likelihood of success.”
Dr. Griauzde pointed out that newer antiobesity drugs can be added to any diet to decrease appetite and enhance adherence.
Dr. Griauzde also observed, “We can label a very-low-carbohydrate diet ‘extreme,’ but maybe, from the patient’s perspective, it’s extreme to take 200 units of insulin a day. If you can give them the opportunity to discontinue use of the insulin by following a very-low-carbohydrate dietary pattern, that is the opportunity that our patients deserve to have.”
But overall, she agreed with Dr. Kirkpatrick about individualizing any dietary approach: “We will never know from any of the trials that have been done or that will be done in the future what diet is best for an individual patient. ... Our job is to help our patients find the dietary approach that works best for them.”
Dr. Kirkpatrick is a clinical scientist with Midwest Biomedical Research, which has received funding from various food and pharmaceutical companies. She has not received any direct funding. Dr. Yancy is a consultant for The Simply Good Foods Co. Dr. Griauzde has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Diabetes drug class appears to reduce recurrent gout flares
The glucose-lowering drug class sodium-glucose cotransporter 2 (SGLT2) inhibitors appear to reduce the risk for recurrent gout flares in people with gout and type 2 diabetes, and to lessen excess mortality in those individuals, compared with those who initiated other types of glucose-lowering medications, new data suggest.
Among nearly 6,000 adults with both type 2 diabetes and gout from a U.K. primary care database, initiation of SGLT2 inhibitor treatment was associated with 19% fewer recurrent gout flares and 29% lower mortality.
Moreover, unlike other urate-lowering therapies, there were no apparent transient increases in the risk of gout flares after initiating therapy, Jie Wei, PhD, of Health Management Center, Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in JAMA Network Open.
These results are important because current management of gout is suboptimal. Many patients either don’t receive adequate urate-lowering therapies such as allopurinol or stop taking them, Dr. Wei and colleagues said.
In addition to lowering glucose, SGLT2 inhibitors also reduce the risk for major adverse cardiovascular events and all-cause mortality in people regardless of their diabetes status. Previous studies have also found that SGLT2 inhibitors reduce the risk for developing gout and of gout flares.
Asked to comment, gout specialist John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, said in an interview: “I think it’s a well-done paper, with a large dataset. I think it just reinforces the findings from the other papers. Mostly anything that lowers uric acid levels is going to lower recurrent gout attacks, so it all makes sense.”
However, while Dr. FitzGerald thinks the drug class is a good option for people with diabetes or cardiorenal indications for them who also have gout, he doesn’t envision it as first-line for most other patients with gout. “The current treatments are very effective. Allopurinol brings down uric acid levels by 5-7 points. There are patients who fail allopurinol, but those are less than 5%.”
The most common reason patients stop taking allopurinol is the frequent initial gout flare. But that’s preventable, Dr. FitzGerald said, either by titrating up slowly, or by adding colchicine along with it. “By going slowly, you can avoid that flare risk. I think that’s what’s going on with the SGLT2 inhibitor. It’s not a dramatic urate-lowering drug, but it is clinically meaningful. I think that’s what this paper is showing.”
But, he noted, “I think there are so many reasons to start the SGLT2 inhibitors that if somebody also has gout, all the better. And, if somebody is on the margin with diabetes and gout control and can’t go with allopurinol, it would be great to add for both conditions.”
Less gout recurrence, lower mortality
The retrospective study was conducted from Jan. 1, 2013, to March 31, 2022. Among 5,931 patients with both type 2 diabetes and gout, 1,548 (26.1%) initiated an SGLT2 inhibitor (dapagliflozin, empagliflozin, or canagliflozin), while 4,383 (73.9%) initiated treatment with other active comparators, mostly (92.6%) dipeptidyl peptidase–4 inhibitors.
Gout flares were identified in the charts for a total of 86% of the participants. The weighted incidence rates for the first recurrent flare were 32.4 versus 41.2 per 1,000 person-years in the SGLT2 inhibitor versus comparator groups, with a weighted absolute rate difference of –8.8/1,000 and weighted hazard ratio of 0.81, a significant difference.
All-cause mortality was 18.8 versus 24.9 per 1,000 person-years, respectively, giving an HR of 0.71 at 5-year follow-up.
Dr. FitzGerald, who chaired the American College of Rheumatology’s 2020 gout guidelines, said he anticipates that the SGLT2 inhibitors will be mentioned in the next update to the ACR’s now “living” guidelines, although he was not speaking on the organization’s behalf.
“We talk about losartan in the current [ACR guidelines], about its specific uric acid–lowering effect. Drugs can make uric acid worse or better. For example, thiazides make it higher. I think the SGLT2 [inhibitors] are important, but I don’t think they’re huge. The study is great, and I think the drugs are great, but I don’t think they will change the way gout is managed.”
This work was supported by grants from the National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders, and from the Natural Science Foundation of Hunan Province. Dr. Wei reported receiving grant funding from Xiangya Hospital Central South University Project Program of National Clinical Research Center for Geriatric Disorders and the Science and Technology Department of Hunan Province, the Natural Science Foundation of Hunan Province, during the conduct of the study. Dr. FitzGerald reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The glucose-lowering drug class sodium-glucose cotransporter 2 (SGLT2) inhibitors appear to reduce the risk for recurrent gout flares in people with gout and type 2 diabetes, and to lessen excess mortality in those individuals, compared with those who initiated other types of glucose-lowering medications, new data suggest.
Among nearly 6,000 adults with both type 2 diabetes and gout from a U.K. primary care database, initiation of SGLT2 inhibitor treatment was associated with 19% fewer recurrent gout flares and 29% lower mortality.
Moreover, unlike other urate-lowering therapies, there were no apparent transient increases in the risk of gout flares after initiating therapy, Jie Wei, PhD, of Health Management Center, Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in JAMA Network Open.
These results are important because current management of gout is suboptimal. Many patients either don’t receive adequate urate-lowering therapies such as allopurinol or stop taking them, Dr. Wei and colleagues said.
In addition to lowering glucose, SGLT2 inhibitors also reduce the risk for major adverse cardiovascular events and all-cause mortality in people regardless of their diabetes status. Previous studies have also found that SGLT2 inhibitors reduce the risk for developing gout and of gout flares.
Asked to comment, gout specialist John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, said in an interview: “I think it’s a well-done paper, with a large dataset. I think it just reinforces the findings from the other papers. Mostly anything that lowers uric acid levels is going to lower recurrent gout attacks, so it all makes sense.”
However, while Dr. FitzGerald thinks the drug class is a good option for people with diabetes or cardiorenal indications for them who also have gout, he doesn’t envision it as first-line for most other patients with gout. “The current treatments are very effective. Allopurinol brings down uric acid levels by 5-7 points. There are patients who fail allopurinol, but those are less than 5%.”
The most common reason patients stop taking allopurinol is the frequent initial gout flare. But that’s preventable, Dr. FitzGerald said, either by titrating up slowly, or by adding colchicine along with it. “By going slowly, you can avoid that flare risk. I think that’s what’s going on with the SGLT2 inhibitor. It’s not a dramatic urate-lowering drug, but it is clinically meaningful. I think that’s what this paper is showing.”
But, he noted, “I think there are so many reasons to start the SGLT2 inhibitors that if somebody also has gout, all the better. And, if somebody is on the margin with diabetes and gout control and can’t go with allopurinol, it would be great to add for both conditions.”
Less gout recurrence, lower mortality
The retrospective study was conducted from Jan. 1, 2013, to March 31, 2022. Among 5,931 patients with both type 2 diabetes and gout, 1,548 (26.1%) initiated an SGLT2 inhibitor (dapagliflozin, empagliflozin, or canagliflozin), while 4,383 (73.9%) initiated treatment with other active comparators, mostly (92.6%) dipeptidyl peptidase–4 inhibitors.
Gout flares were identified in the charts for a total of 86% of the participants. The weighted incidence rates for the first recurrent flare were 32.4 versus 41.2 per 1,000 person-years in the SGLT2 inhibitor versus comparator groups, with a weighted absolute rate difference of –8.8/1,000 and weighted hazard ratio of 0.81, a significant difference.
All-cause mortality was 18.8 versus 24.9 per 1,000 person-years, respectively, giving an HR of 0.71 at 5-year follow-up.
Dr. FitzGerald, who chaired the American College of Rheumatology’s 2020 gout guidelines, said he anticipates that the SGLT2 inhibitors will be mentioned in the next update to the ACR’s now “living” guidelines, although he was not speaking on the organization’s behalf.
“We talk about losartan in the current [ACR guidelines], about its specific uric acid–lowering effect. Drugs can make uric acid worse or better. For example, thiazides make it higher. I think the SGLT2 [inhibitors] are important, but I don’t think they’re huge. The study is great, and I think the drugs are great, but I don’t think they will change the way gout is managed.”
This work was supported by grants from the National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders, and from the Natural Science Foundation of Hunan Province. Dr. Wei reported receiving grant funding from Xiangya Hospital Central South University Project Program of National Clinical Research Center for Geriatric Disorders and the Science and Technology Department of Hunan Province, the Natural Science Foundation of Hunan Province, during the conduct of the study. Dr. FitzGerald reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The glucose-lowering drug class sodium-glucose cotransporter 2 (SGLT2) inhibitors appear to reduce the risk for recurrent gout flares in people with gout and type 2 diabetes, and to lessen excess mortality in those individuals, compared with those who initiated other types of glucose-lowering medications, new data suggest.
Among nearly 6,000 adults with both type 2 diabetes and gout from a U.K. primary care database, initiation of SGLT2 inhibitor treatment was associated with 19% fewer recurrent gout flares and 29% lower mortality.
Moreover, unlike other urate-lowering therapies, there were no apparent transient increases in the risk of gout flares after initiating therapy, Jie Wei, PhD, of Health Management Center, Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in JAMA Network Open.
These results are important because current management of gout is suboptimal. Many patients either don’t receive adequate urate-lowering therapies such as allopurinol or stop taking them, Dr. Wei and colleagues said.
In addition to lowering glucose, SGLT2 inhibitors also reduce the risk for major adverse cardiovascular events and all-cause mortality in people regardless of their diabetes status. Previous studies have also found that SGLT2 inhibitors reduce the risk for developing gout and of gout flares.
Asked to comment, gout specialist John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, said in an interview: “I think it’s a well-done paper, with a large dataset. I think it just reinforces the findings from the other papers. Mostly anything that lowers uric acid levels is going to lower recurrent gout attacks, so it all makes sense.”
However, while Dr. FitzGerald thinks the drug class is a good option for people with diabetes or cardiorenal indications for them who also have gout, he doesn’t envision it as first-line for most other patients with gout. “The current treatments are very effective. Allopurinol brings down uric acid levels by 5-7 points. There are patients who fail allopurinol, but those are less than 5%.”
The most common reason patients stop taking allopurinol is the frequent initial gout flare. But that’s preventable, Dr. FitzGerald said, either by titrating up slowly, or by adding colchicine along with it. “By going slowly, you can avoid that flare risk. I think that’s what’s going on with the SGLT2 inhibitor. It’s not a dramatic urate-lowering drug, but it is clinically meaningful. I think that’s what this paper is showing.”
But, he noted, “I think there are so many reasons to start the SGLT2 inhibitors that if somebody also has gout, all the better. And, if somebody is on the margin with diabetes and gout control and can’t go with allopurinol, it would be great to add for both conditions.”
Less gout recurrence, lower mortality
The retrospective study was conducted from Jan. 1, 2013, to March 31, 2022. Among 5,931 patients with both type 2 diabetes and gout, 1,548 (26.1%) initiated an SGLT2 inhibitor (dapagliflozin, empagliflozin, or canagliflozin), while 4,383 (73.9%) initiated treatment with other active comparators, mostly (92.6%) dipeptidyl peptidase–4 inhibitors.
Gout flares were identified in the charts for a total of 86% of the participants. The weighted incidence rates for the first recurrent flare were 32.4 versus 41.2 per 1,000 person-years in the SGLT2 inhibitor versus comparator groups, with a weighted absolute rate difference of –8.8/1,000 and weighted hazard ratio of 0.81, a significant difference.
All-cause mortality was 18.8 versus 24.9 per 1,000 person-years, respectively, giving an HR of 0.71 at 5-year follow-up.
Dr. FitzGerald, who chaired the American College of Rheumatology’s 2020 gout guidelines, said he anticipates that the SGLT2 inhibitors will be mentioned in the next update to the ACR’s now “living” guidelines, although he was not speaking on the organization’s behalf.
“We talk about losartan in the current [ACR guidelines], about its specific uric acid–lowering effect. Drugs can make uric acid worse or better. For example, thiazides make it higher. I think the SGLT2 [inhibitors] are important, but I don’t think they’re huge. The study is great, and I think the drugs are great, but I don’t think they will change the way gout is managed.”
This work was supported by grants from the National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of National Clinical Research Center for Geriatric Disorders, and from the Natural Science Foundation of Hunan Province. Dr. Wei reported receiving grant funding from Xiangya Hospital Central South University Project Program of National Clinical Research Center for Geriatric Disorders and the Science and Technology Department of Hunan Province, the Natural Science Foundation of Hunan Province, during the conduct of the study. Dr. FitzGerald reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Screening finds high rates of CVD in diabetes, COPD patients
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , compared with usual care, in a Dutch study involving more than 1,200 people and 25 primary care practices.
Scaling up this program to larger populations could potentially uncover huge numbers of currently unrecognized people with CVD given the large number of adults with type 2 diabetes plus those with COPD, Amy Groenewegen, MD, said at the annual congress of the European Society of Cardiology.
“I think this screening is ready for routine use, but it could be followed by prospective studies that investigate whether it produces more benefits in patient-centered outcomes,” Dr. Groenewegen said in a press briefing. She stressed that it has not yet been clearly proven that patients with these chronic diseases are better off long term when their CVD is detected sooner using the tested approach.
“We need simple ways to identify relevant patients for additional screening and potential treatment” of CVD, commented Lars Kober, MD, designated discussant at the Congress and a cardiologist and professor at Rigshospitalet, Copenhagen University Hospital.
A ‘very simple’ symptom questionnaire
The study is important because it tested a “very simple” symptom questionnaire as the initial screening phase, yet resulted in a CVD diagnostic rate that was two- to threefold higher than in the control patients managed with usual care, Dr. Kober noted.
The Reviving the Early Diagnosis of CVD (RED-CVD) trial randomized 14 primary care practices in the Netherlands to apply a structured screening protocol to adults with type 2 diabetes or COPD, and another 11 practices that served as controls and provided their patients with usual care.
The study included 624 people in the screening arm and 592 in the usual-care arm. Their average age was about 68 years. In the screening arm, 87% had type 2 diabetes and 20% had COPD, including 6.3% with both. In the usual-care arm, 86% had type 2 diabetes, 21% had COPD, with 7.4% having both.
About a quarter of the study cohort had a history of a CVD diagnosis, but they were included for their potential for developing another form of CVD. The study considered three types of CVD: coronary artery disease, heart failure, and atrial fibrillation.
The CVD screening protocol began with an 11-question survey, completed by patients, that asked about their symptoms. The survey was devised by a research team at the University Medical Center Groningen, the Netherlands, who collaborated on the study.
The second phase for people who had suggestive symptoms was a physical examination, measurement of serum N-terminal pro-brain natriuretic peptide (elevated levels signal incident heart failure), and an ECG. People who continued to show findings consistent with CVD in this phase were then referred on a discretionary basis by the attending physician to a specialist.
More than doubling the CVD diagnosis rate
The screening program produced a total of 50 new CVD diagnoses in the screening cohort (8%) and 18 in the control, usual-care arm (3%), for the study’s primary endpoint. The greatest number of events involved heart failure, followed by coronary disease.
The screening questionnaire identified 70% of the people who completed it with suggestive symptoms, such as shortness of breath, claudication, or palpitations. The follow-up assessments of phase two narrowed the group with possible new CVD down to 44% of the people in this arm, and the participating physicians referred 39% to a specialist.
An analysis that adjusted for several demographic and clinical variables and excluded nonobstructive coronary disease as a new CVD diagnosis showed that the systematic screening approach resulted in 2.4-fold more new diagnoses than usual care, reported Dr. Groenewegen, an epidemiologist at University Medical Center Utrecht, the Netherlands.
RED-CVD received no commercial funding. Dr. Groenewegen disclosed no relevant financial relationships. Dr. Kober has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk.
A version of this article first appeared on Medscape.com.
AT ESC CONGRESS 2023
FDA clears new capabilities for diabetes app BlueStar
The latest clearance, announced on Aug. 23, enables the app-based platform to provide bolus insulin dose recommendations that are based on glucose and trend data from a compatible continuous glucose monitoring (CGM) device. On Aug. 15, the FDA cleared the BlueStar to use connected insulin dosing data in personalized bolus insulin dosing recommendations.
“Welldoc is the first company to receive clearance for a CGM-informed bolus calculator specifically designed for adults who manage their diabetes with multiple daily injections of insulin,” according to a company statement.
“With this clearance, Welldoc is filling a significant gap for people who require complex insulin regimens. By connecting directly with CGM data and using both glucose values and trend arrows, the BlueStar solution will provide precise and in-the-moment insulin dosing guidance directly to individuals, helping them reach their glucose targets,” endocrinologist Grazia Aleppo, MD, of Northwestern University, Chicago, said in the statement.
The new features extend the platform’s existing digital diet and lifestyle coaching capabilities. Previous FDA clearances included expansions to use most types of available insulins, including bolus and premixed insulin titration for patients with type 2 diabetes, in September 2021 and for basal insulin adjustment in June 2020.
Dr. Aleppo was a principal investigator in Welldoc’s clinical validation study for BlueStar.
A version of this article first appeared on Medscape.com.
The latest clearance, announced on Aug. 23, enables the app-based platform to provide bolus insulin dose recommendations that are based on glucose and trend data from a compatible continuous glucose monitoring (CGM) device. On Aug. 15, the FDA cleared the BlueStar to use connected insulin dosing data in personalized bolus insulin dosing recommendations.
“Welldoc is the first company to receive clearance for a CGM-informed bolus calculator specifically designed for adults who manage their diabetes with multiple daily injections of insulin,” according to a company statement.
“With this clearance, Welldoc is filling a significant gap for people who require complex insulin regimens. By connecting directly with CGM data and using both glucose values and trend arrows, the BlueStar solution will provide precise and in-the-moment insulin dosing guidance directly to individuals, helping them reach their glucose targets,” endocrinologist Grazia Aleppo, MD, of Northwestern University, Chicago, said in the statement.
The new features extend the platform’s existing digital diet and lifestyle coaching capabilities. Previous FDA clearances included expansions to use most types of available insulins, including bolus and premixed insulin titration for patients with type 2 diabetes, in September 2021 and for basal insulin adjustment in June 2020.
Dr. Aleppo was a principal investigator in Welldoc’s clinical validation study for BlueStar.
A version of this article first appeared on Medscape.com.
The latest clearance, announced on Aug. 23, enables the app-based platform to provide bolus insulin dose recommendations that are based on glucose and trend data from a compatible continuous glucose monitoring (CGM) device. On Aug. 15, the FDA cleared the BlueStar to use connected insulin dosing data in personalized bolus insulin dosing recommendations.
“Welldoc is the first company to receive clearance for a CGM-informed bolus calculator specifically designed for adults who manage their diabetes with multiple daily injections of insulin,” according to a company statement.
“With this clearance, Welldoc is filling a significant gap for people who require complex insulin regimens. By connecting directly with CGM data and using both glucose values and trend arrows, the BlueStar solution will provide precise and in-the-moment insulin dosing guidance directly to individuals, helping them reach their glucose targets,” endocrinologist Grazia Aleppo, MD, of Northwestern University, Chicago, said in the statement.
The new features extend the platform’s existing digital diet and lifestyle coaching capabilities. Previous FDA clearances included expansions to use most types of available insulins, including bolus and premixed insulin titration for patients with type 2 diabetes, in September 2021 and for basal insulin adjustment in June 2020.
Dr. Aleppo was a principal investigator in Welldoc’s clinical validation study for BlueStar.
A version of this article first appeared on Medscape.com.
Medicare announces 10 drugs targeted for price cuts in 2026
People on Medicare may in 2026 see prices drop for 10 medicines, including pricey diabetes, cancer, blood clot, and arthritis treatments, if advocates for federal drug-price negotiations can implement their plans amid tough opposition.
It’s unclear at this time, though, how these negotiations will play out. The Chamber of Commerce has sided with pharmaceutical companies in bids to block direct Medicare negotiation of drug prices. Many influential Republicans in Congress oppose this plan, which has deep support from both Democrats and AARP.
While facing strong opposition to negotiations, the Centers for Medicare & Medicaid Services sought in its announcement to illustrate the high costs of the selected medicines.
CMS provided data on total Part D costs for selected medicines for the period from June 2022 to May 2023, along with tallies of the number of people taking these drugs. The 10 selected medicines are as follows:
- Eliquis (generic name: apixaban), used to prevent and treat serious blood clots. It is taken by about 3.7 million people through Part D plans. The estimated cost is $16.4 billion.
- Jardiance (generic name: empagliflozin), used for diabetes and heart failure. It is taken by almost 1.6 million people through Part D plans. The estimated cost is $7.06 billion.
- Xarelto (generic name: rivaroxaban), used for blood clots. It is taken by about 1.3 million people through Part D plans. The estimated cost is $6 billion.
- Januvia (generic name: sitagliptin), used for diabetes. It is taken by about 869,00 people through Part D plans. The estimated cost is $4.1 billion.
- Farxiga (generic name: dapagliflozin), used for diabetes, heart failure, and chronic kidney disease. It is taken by about 799,000 people through Part D plans. The estimated cost is almost $3.3 billion.
- Entresto (generic name: sacubitril/valsartan), used to treat heart failure. It is taken by 587,000 people through Part D plans. The estimated cost is $2.9 billion.
- Enbrel( generic name: etanercept), used for rheumatoid arthritis, psoriasis, and psoriatic arthritis. It is taken by 48,000 people through Part D plans. The estimated cost is $2.8 billion.
- Imbruvica (generic name: ibrutinib), used to treat some blood cancers. It is taken by about 20,000 people in Part D plans. The estimated cost is $2.7 billion.
- Stelara (generic name: ustekinumab), used to treat plaque psoriasis, psoriatic arthritis, or certain bowel conditions (Crohn’s disease, ulcerative colitis). It is used by about 22,000 people through Part D plans. The estimated cost is $2.6 billion.
- Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill. These are forms of insulin used to treat diabetes. They are used by about 777,000 people through Part D plans. The estimated cost is $2.6 billion.
A vocal critic of Medicare drug negotiations, Joel White, president of the Council for Affordable Health Coverage, called the announcement of the 10 drugs selected for negotiation “a hollow victory lap.” A former Republican staffer on the House Ways and Means Committee, Mr. White aided with the development of the Medicare Part D plans and has kept tabs on the pharmacy programs since its launch in 2006.
“No one’s costs will go down now or for years because of this announcement” about Part D negotiations, Mr. White said in a statement.
According to its website, CAHC includes among its members the American Academy of Ophthalmology as well as some patient groups, drugmakers, such as Johnson & Johnson, and insurers and industry groups, such as the National Association of Manufacturers.
Separately, the influential Chamber of Commerce is making a strong push to at least delay the implementation of the Medicare Part D drug negotiations. On Aug. 28, the chamber released a letter sent to the Biden administration, raising concerns about a “rush” to implement the provisions of the Inflation Reduction Act.
The chamber also has filed suit to challenge the drug negotiation provisions of the Inflation Reduction Act, requesting that the court issue a preliminary injunction by Oct. 1, 2023.
Other pending legal challenges to direct Medicare drug negotiations include suits filed by Merck, Bristol-Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, and AstraZeneca, according to an email from Pharmaceutical Research and Manufacturers of America. PhRMA also said it is a party to a case.
In addition, the three congressional Republicans with most direct influence over Medicare policy issued on Aug. 29 a joint statement outlining their objections to the planned negotiations on drug prices.
This drug-negotiation proposal is “an unworkable, legally dubious scheme that will lead to higher prices for new drugs coming to market, stifle the development of new cures, and destroy jobs,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-Wash.), House Ways and Means Committee Chair Jason Smith (R-Mo.), and Senate Finance Committee Ranking Member Mike Crapo (R-Idaho).
Democrats were equally firm and vocal in their support of the negotiations. Senate Finance Chairman Ron Wyden (D-Ore.) issued a statement on Aug. 29 that said the release of the list of the 10 drugs selected for Medicare drug negotiations is part of a “seismic shift in the relationship between Big Pharma, the federal government, and seniors who are counting on lower prices.
“I will be following the negotiation process closely and will fight any attempt by Big Pharma to undo or undermine the progress that’s been made,” Mr. Wyden said.
In addition, AARP issued a statement of its continued support for Medicare drug negotiations.
“The No. 1 reason seniors skip or ration their prescriptions is because they can’t afford them. This must stop,” said AARP executive vice president and chief advocacy and engagement officer Nancy LeaMond in the statement. “The big drug companies and their allies continue suing to overturn the Medicare drug price negotiation program to keep up their price gouging. We can’t allow seniors to be Big Pharma’s cash machine anymore.”
A version of this article first appeared on Medscape.com.
People on Medicare may in 2026 see prices drop for 10 medicines, including pricey diabetes, cancer, blood clot, and arthritis treatments, if advocates for federal drug-price negotiations can implement their plans amid tough opposition.
It’s unclear at this time, though, how these negotiations will play out. The Chamber of Commerce has sided with pharmaceutical companies in bids to block direct Medicare negotiation of drug prices. Many influential Republicans in Congress oppose this plan, which has deep support from both Democrats and AARP.
While facing strong opposition to negotiations, the Centers for Medicare & Medicaid Services sought in its announcement to illustrate the high costs of the selected medicines.
CMS provided data on total Part D costs for selected medicines for the period from June 2022 to May 2023, along with tallies of the number of people taking these drugs. The 10 selected medicines are as follows:
- Eliquis (generic name: apixaban), used to prevent and treat serious blood clots. It is taken by about 3.7 million people through Part D plans. The estimated cost is $16.4 billion.
- Jardiance (generic name: empagliflozin), used for diabetes and heart failure. It is taken by almost 1.6 million people through Part D plans. The estimated cost is $7.06 billion.
- Xarelto (generic name: rivaroxaban), used for blood clots. It is taken by about 1.3 million people through Part D plans. The estimated cost is $6 billion.
- Januvia (generic name: sitagliptin), used for diabetes. It is taken by about 869,00 people through Part D plans. The estimated cost is $4.1 billion.
- Farxiga (generic name: dapagliflozin), used for diabetes, heart failure, and chronic kidney disease. It is taken by about 799,000 people through Part D plans. The estimated cost is almost $3.3 billion.
- Entresto (generic name: sacubitril/valsartan), used to treat heart failure. It is taken by 587,000 people through Part D plans. The estimated cost is $2.9 billion.
- Enbrel( generic name: etanercept), used for rheumatoid arthritis, psoriasis, and psoriatic arthritis. It is taken by 48,000 people through Part D plans. The estimated cost is $2.8 billion.
- Imbruvica (generic name: ibrutinib), used to treat some blood cancers. It is taken by about 20,000 people in Part D plans. The estimated cost is $2.7 billion.
- Stelara (generic name: ustekinumab), used to treat plaque psoriasis, psoriatic arthritis, or certain bowel conditions (Crohn’s disease, ulcerative colitis). It is used by about 22,000 people through Part D plans. The estimated cost is $2.6 billion.
- Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill. These are forms of insulin used to treat diabetes. They are used by about 777,000 people through Part D plans. The estimated cost is $2.6 billion.
A vocal critic of Medicare drug negotiations, Joel White, president of the Council for Affordable Health Coverage, called the announcement of the 10 drugs selected for negotiation “a hollow victory lap.” A former Republican staffer on the House Ways and Means Committee, Mr. White aided with the development of the Medicare Part D plans and has kept tabs on the pharmacy programs since its launch in 2006.
“No one’s costs will go down now or for years because of this announcement” about Part D negotiations, Mr. White said in a statement.
According to its website, CAHC includes among its members the American Academy of Ophthalmology as well as some patient groups, drugmakers, such as Johnson & Johnson, and insurers and industry groups, such as the National Association of Manufacturers.
Separately, the influential Chamber of Commerce is making a strong push to at least delay the implementation of the Medicare Part D drug negotiations. On Aug. 28, the chamber released a letter sent to the Biden administration, raising concerns about a “rush” to implement the provisions of the Inflation Reduction Act.
The chamber also has filed suit to challenge the drug negotiation provisions of the Inflation Reduction Act, requesting that the court issue a preliminary injunction by Oct. 1, 2023.
Other pending legal challenges to direct Medicare drug negotiations include suits filed by Merck, Bristol-Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, and AstraZeneca, according to an email from Pharmaceutical Research and Manufacturers of America. PhRMA also said it is a party to a case.
In addition, the three congressional Republicans with most direct influence over Medicare policy issued on Aug. 29 a joint statement outlining their objections to the planned negotiations on drug prices.
This drug-negotiation proposal is “an unworkable, legally dubious scheme that will lead to higher prices for new drugs coming to market, stifle the development of new cures, and destroy jobs,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-Wash.), House Ways and Means Committee Chair Jason Smith (R-Mo.), and Senate Finance Committee Ranking Member Mike Crapo (R-Idaho).
Democrats were equally firm and vocal in their support of the negotiations. Senate Finance Chairman Ron Wyden (D-Ore.) issued a statement on Aug. 29 that said the release of the list of the 10 drugs selected for Medicare drug negotiations is part of a “seismic shift in the relationship between Big Pharma, the federal government, and seniors who are counting on lower prices.
“I will be following the negotiation process closely and will fight any attempt by Big Pharma to undo or undermine the progress that’s been made,” Mr. Wyden said.
In addition, AARP issued a statement of its continued support for Medicare drug negotiations.
“The No. 1 reason seniors skip or ration their prescriptions is because they can’t afford them. This must stop,” said AARP executive vice president and chief advocacy and engagement officer Nancy LeaMond in the statement. “The big drug companies and their allies continue suing to overturn the Medicare drug price negotiation program to keep up their price gouging. We can’t allow seniors to be Big Pharma’s cash machine anymore.”
A version of this article first appeared on Medscape.com.
People on Medicare may in 2026 see prices drop for 10 medicines, including pricey diabetes, cancer, blood clot, and arthritis treatments, if advocates for federal drug-price negotiations can implement their plans amid tough opposition.
It’s unclear at this time, though, how these negotiations will play out. The Chamber of Commerce has sided with pharmaceutical companies in bids to block direct Medicare negotiation of drug prices. Many influential Republicans in Congress oppose this plan, which has deep support from both Democrats and AARP.
While facing strong opposition to negotiations, the Centers for Medicare & Medicaid Services sought in its announcement to illustrate the high costs of the selected medicines.
CMS provided data on total Part D costs for selected medicines for the period from June 2022 to May 2023, along with tallies of the number of people taking these drugs. The 10 selected medicines are as follows:
- Eliquis (generic name: apixaban), used to prevent and treat serious blood clots. It is taken by about 3.7 million people through Part D plans. The estimated cost is $16.4 billion.
- Jardiance (generic name: empagliflozin), used for diabetes and heart failure. It is taken by almost 1.6 million people through Part D plans. The estimated cost is $7.06 billion.
- Xarelto (generic name: rivaroxaban), used for blood clots. It is taken by about 1.3 million people through Part D plans. The estimated cost is $6 billion.
- Januvia (generic name: sitagliptin), used for diabetes. It is taken by about 869,00 people through Part D plans. The estimated cost is $4.1 billion.
- Farxiga (generic name: dapagliflozin), used for diabetes, heart failure, and chronic kidney disease. It is taken by about 799,000 people through Part D plans. The estimated cost is almost $3.3 billion.
- Entresto (generic name: sacubitril/valsartan), used to treat heart failure. It is taken by 587,000 people through Part D plans. The estimated cost is $2.9 billion.
- Enbrel( generic name: etanercept), used for rheumatoid arthritis, psoriasis, and psoriatic arthritis. It is taken by 48,000 people through Part D plans. The estimated cost is $2.8 billion.
- Imbruvica (generic name: ibrutinib), used to treat some blood cancers. It is taken by about 20,000 people in Part D plans. The estimated cost is $2.7 billion.
- Stelara (generic name: ustekinumab), used to treat plaque psoriasis, psoriatic arthritis, or certain bowel conditions (Crohn’s disease, ulcerative colitis). It is used by about 22,000 people through Part D plans. The estimated cost is $2.6 billion.
- Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill. These are forms of insulin used to treat diabetes. They are used by about 777,000 people through Part D plans. The estimated cost is $2.6 billion.
A vocal critic of Medicare drug negotiations, Joel White, president of the Council for Affordable Health Coverage, called the announcement of the 10 drugs selected for negotiation “a hollow victory lap.” A former Republican staffer on the House Ways and Means Committee, Mr. White aided with the development of the Medicare Part D plans and has kept tabs on the pharmacy programs since its launch in 2006.
“No one’s costs will go down now or for years because of this announcement” about Part D negotiations, Mr. White said in a statement.
According to its website, CAHC includes among its members the American Academy of Ophthalmology as well as some patient groups, drugmakers, such as Johnson & Johnson, and insurers and industry groups, such as the National Association of Manufacturers.
Separately, the influential Chamber of Commerce is making a strong push to at least delay the implementation of the Medicare Part D drug negotiations. On Aug. 28, the chamber released a letter sent to the Biden administration, raising concerns about a “rush” to implement the provisions of the Inflation Reduction Act.
The chamber also has filed suit to challenge the drug negotiation provisions of the Inflation Reduction Act, requesting that the court issue a preliminary injunction by Oct. 1, 2023.
Other pending legal challenges to direct Medicare drug negotiations include suits filed by Merck, Bristol-Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, and AstraZeneca, according to an email from Pharmaceutical Research and Manufacturers of America. PhRMA also said it is a party to a case.
In addition, the three congressional Republicans with most direct influence over Medicare policy issued on Aug. 29 a joint statement outlining their objections to the planned negotiations on drug prices.
This drug-negotiation proposal is “an unworkable, legally dubious scheme that will lead to higher prices for new drugs coming to market, stifle the development of new cures, and destroy jobs,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-Wash.), House Ways and Means Committee Chair Jason Smith (R-Mo.), and Senate Finance Committee Ranking Member Mike Crapo (R-Idaho).
Democrats were equally firm and vocal in their support of the negotiations. Senate Finance Chairman Ron Wyden (D-Ore.) issued a statement on Aug. 29 that said the release of the list of the 10 drugs selected for Medicare drug negotiations is part of a “seismic shift in the relationship between Big Pharma, the federal government, and seniors who are counting on lower prices.
“I will be following the negotiation process closely and will fight any attempt by Big Pharma to undo or undermine the progress that’s been made,” Mr. Wyden said.
In addition, AARP issued a statement of its continued support for Medicare drug negotiations.
“The No. 1 reason seniors skip or ration their prescriptions is because they can’t afford them. This must stop,” said AARP executive vice president and chief advocacy and engagement officer Nancy LeaMond in the statement. “The big drug companies and their allies continue suing to overturn the Medicare drug price negotiation program to keep up their price gouging. We can’t allow seniors to be Big Pharma’s cash machine anymore.”
A version of this article first appeared on Medscape.com.
Even an hour’s walk a week lowers risk in type 2 diabetes
although the impact on retinopathy is weaker, reveals a cohort study of U.K. individuals.
The research, based on data from more than 18,000 participants in the U.K. Biobank, suggests that the minimal level of self-reported activity to reduce the risk for both neuropathy and nephropathy may be the equivalent of less than 1.5 hours of walking per week.
The results are “encouraging and reassuring for both physicians and patients,” lead author Frederik P.B. Kristensen, MSc, PhD student, department of clinical epidemiology, Aarhus (Denmark) University, said in an interview.
“Our findings are particularly promising for neuropathy since, currently, no disease-modifying treatment exists, and there are limited preventive strategies available.”
Mr. Kristensen highlighted that “most diabetes research has focused on all-cause mortality and macrovascular complications. In the current study, we also found the same pattern for microvascular complications: Even small amounts of physical activity will benefit your health status.”
The minimal level of activity they identified, he said, is also an “achievable [goal] for most type 2 diabetes patients.”
Mr. Kristensen added, however, that the study was limited by excluding individuals with limited mobility and those living in temporary accommodation or care homes.
And prospective studies are required to determine the dose-response relationship between total, not just leisure-time, activity – ideally measured objectively – and risk for microvascular complications, he observed.
The research was published recently in Diabetes Care.
Impact of exercise on microvascular complications in T2D has been uncertain
The authors point out that microvascular complications – such as nerve damage (neuropathy), kidney problems (nephropathy), and eye complications (retinopathy) – occur in more than 50% of individuals with type 2 diabetes and have a “substantial impact” on quality of life, on top of the impact of macrovascular complications (such as cardiovascular disease), disability, and mortality.
Although physical activity is seen as a “cornerstone in the multifactorial management of type 2 diabetes because of its beneficial effects on metabolic risk factors,” the impact on microvascular complications is “uncertain” and the evidence is limited and “conflicting.”
The researchers therefore sought to examine the dose-response association, including the minimal effective level, between leisure-time physical activity and neuropathy, nephropathy, and retinopathy.
They conducted a cohort study of individuals aged 37-82 years from the U.K. Biobank who had type 2 diabetes, which was identified using the Eastwood algorithm and/or an A1c greater than or equal to 48 mmol/mol (6.5%).
Individuals with type 1 diabetes or gestational diabetes were excluded, as were those with major disabling somatic disorders, neurodegenerative diseases, and mental disorders, among others.
Leisure-time physical activity was based on the self-reported frequency, duration, and types of physical activities and was combined to calculate the total leisure time activity in MET-hours per week.
Using the American Diabetes Association/World Health Organization recommendations of 150-300 minutes of moderate to vigorous leisure-time physical activity per week, the researchers determined the recommended moderate activity level to be 150 minutes, (equivalent to 2.5 hours, or 7.5 MET-hours per week).
In all, 18,092 individuals with type 2 diabetes were included in the analysis, of whom 37% were women. The mean age was 60 years.
Ten percent of participants performed no leisure-time physical activity, 38% performed activity below the threshold for moderate activity, 20% performed at the recommended level, and 32% were more active.
Those performing no physical activity were more likely to be women, to be younger, to have a higher body mass index, and to have a greater average A1c, as well as have a more unfavorable sociodemographic and behavioral profile.
Over a median follow-up of 12.1 years, 3.7% of the participants were diagnosed with neuropathy, 10.2% with nephropathy, and 11.7% with retinopathy, equating to an incidence per 1,000 person-years of 3.5, 9,8, and 11.4, respectively.
The researchers found that any level of physical activity was associated with an approximate reduction in the risk for neuropathy and nephropathy.
Multivariate analysis indicated that, compared with no physical activity, activity below the recommended level was associated with an adjusted hazard ratio (aHR) for neuropathy of 0.71, whereas the aHR for activity at the recommended level was 0.73 and that for activity above the recommended level was 0.67.
The aHR for nephropathy, compared with no physical activity, was 0.79 for activity below the recommended level, 0.80 for activity at the recommended level, and 0.80 for activity above the recommended level.
The association between physical activity and retinopathy was weaker, however, at aHRs of 0.91, 0.91, and 0.98 for activity below, at, and above the recommended level, respectively.
The researchers suggest that this lower association could be due to differences in the etiology of the different forms of microvascular complications.
Hyperglycemia is the key driver in the development of retinopathy, they note, whereas other metabolic risk factors, such as obesity, insulin resistance, inflammation, dyslipidemia, and hypertension, play a role in neuropathy and nephropathy.
The associations were also less pronounced in women.
Mr. Kristensen said that this is “an important area that needs to be addressed.”
“While different rates between men and women regarding incidence of type 2 diabetes, metabolic risk factors, complications, and the initiation of, and adherence to, therapy have been found,” he continued, “the exact mechanisms remain unclear. We need a further understanding of sex-differences in metabolic regulation, as well as in material living conditions, social and psychological factors, and access to health care, which may influence the risk of complications.”
Mr. Kristensen added, “Sex differences may be present in more areas than we are aware.”
Mr. Kristensen is supported by a PhD grant from Aarhus University. Other authors received funding from the Danish Diabetes Association, the Australian National Health and Medical Research Council, the New South Wales Government, the Spanish Ministry of Universities, the European Union NextGenerationEU/PRTR (Plan de Recuperación) through a Margarita Salas contract of the University of Vigo, and the Government of Andalusia, Research Talent Recruitment Programme. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
although the impact on retinopathy is weaker, reveals a cohort study of U.K. individuals.
The research, based on data from more than 18,000 participants in the U.K. Biobank, suggests that the minimal level of self-reported activity to reduce the risk for both neuropathy and nephropathy may be the equivalent of less than 1.5 hours of walking per week.
The results are “encouraging and reassuring for both physicians and patients,” lead author Frederik P.B. Kristensen, MSc, PhD student, department of clinical epidemiology, Aarhus (Denmark) University, said in an interview.
“Our findings are particularly promising for neuropathy since, currently, no disease-modifying treatment exists, and there are limited preventive strategies available.”
Mr. Kristensen highlighted that “most diabetes research has focused on all-cause mortality and macrovascular complications. In the current study, we also found the same pattern for microvascular complications: Even small amounts of physical activity will benefit your health status.”
The minimal level of activity they identified, he said, is also an “achievable [goal] for most type 2 diabetes patients.”
Mr. Kristensen added, however, that the study was limited by excluding individuals with limited mobility and those living in temporary accommodation or care homes.
And prospective studies are required to determine the dose-response relationship between total, not just leisure-time, activity – ideally measured objectively – and risk for microvascular complications, he observed.
The research was published recently in Diabetes Care.
Impact of exercise on microvascular complications in T2D has been uncertain
The authors point out that microvascular complications – such as nerve damage (neuropathy), kidney problems (nephropathy), and eye complications (retinopathy) – occur in more than 50% of individuals with type 2 diabetes and have a “substantial impact” on quality of life, on top of the impact of macrovascular complications (such as cardiovascular disease), disability, and mortality.
Although physical activity is seen as a “cornerstone in the multifactorial management of type 2 diabetes because of its beneficial effects on metabolic risk factors,” the impact on microvascular complications is “uncertain” and the evidence is limited and “conflicting.”
The researchers therefore sought to examine the dose-response association, including the minimal effective level, between leisure-time physical activity and neuropathy, nephropathy, and retinopathy.
They conducted a cohort study of individuals aged 37-82 years from the U.K. Biobank who had type 2 diabetes, which was identified using the Eastwood algorithm and/or an A1c greater than or equal to 48 mmol/mol (6.5%).
Individuals with type 1 diabetes or gestational diabetes were excluded, as were those with major disabling somatic disorders, neurodegenerative diseases, and mental disorders, among others.
Leisure-time physical activity was based on the self-reported frequency, duration, and types of physical activities and was combined to calculate the total leisure time activity in MET-hours per week.
Using the American Diabetes Association/World Health Organization recommendations of 150-300 minutes of moderate to vigorous leisure-time physical activity per week, the researchers determined the recommended moderate activity level to be 150 minutes, (equivalent to 2.5 hours, or 7.5 MET-hours per week).
In all, 18,092 individuals with type 2 diabetes were included in the analysis, of whom 37% were women. The mean age was 60 years.
Ten percent of participants performed no leisure-time physical activity, 38% performed activity below the threshold for moderate activity, 20% performed at the recommended level, and 32% were more active.
Those performing no physical activity were more likely to be women, to be younger, to have a higher body mass index, and to have a greater average A1c, as well as have a more unfavorable sociodemographic and behavioral profile.
Over a median follow-up of 12.1 years, 3.7% of the participants were diagnosed with neuropathy, 10.2% with nephropathy, and 11.7% with retinopathy, equating to an incidence per 1,000 person-years of 3.5, 9,8, and 11.4, respectively.
The researchers found that any level of physical activity was associated with an approximate reduction in the risk for neuropathy and nephropathy.
Multivariate analysis indicated that, compared with no physical activity, activity below the recommended level was associated with an adjusted hazard ratio (aHR) for neuropathy of 0.71, whereas the aHR for activity at the recommended level was 0.73 and that for activity above the recommended level was 0.67.
The aHR for nephropathy, compared with no physical activity, was 0.79 for activity below the recommended level, 0.80 for activity at the recommended level, and 0.80 for activity above the recommended level.
The association between physical activity and retinopathy was weaker, however, at aHRs of 0.91, 0.91, and 0.98 for activity below, at, and above the recommended level, respectively.
The researchers suggest that this lower association could be due to differences in the etiology of the different forms of microvascular complications.
Hyperglycemia is the key driver in the development of retinopathy, they note, whereas other metabolic risk factors, such as obesity, insulin resistance, inflammation, dyslipidemia, and hypertension, play a role in neuropathy and nephropathy.
The associations were also less pronounced in women.
Mr. Kristensen said that this is “an important area that needs to be addressed.”
“While different rates between men and women regarding incidence of type 2 diabetes, metabolic risk factors, complications, and the initiation of, and adherence to, therapy have been found,” he continued, “the exact mechanisms remain unclear. We need a further understanding of sex-differences in metabolic regulation, as well as in material living conditions, social and psychological factors, and access to health care, which may influence the risk of complications.”
Mr. Kristensen added, “Sex differences may be present in more areas than we are aware.”
Mr. Kristensen is supported by a PhD grant from Aarhus University. Other authors received funding from the Danish Diabetes Association, the Australian National Health and Medical Research Council, the New South Wales Government, the Spanish Ministry of Universities, the European Union NextGenerationEU/PRTR (Plan de Recuperación) through a Margarita Salas contract of the University of Vigo, and the Government of Andalusia, Research Talent Recruitment Programme. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
although the impact on retinopathy is weaker, reveals a cohort study of U.K. individuals.
The research, based on data from more than 18,000 participants in the U.K. Biobank, suggests that the minimal level of self-reported activity to reduce the risk for both neuropathy and nephropathy may be the equivalent of less than 1.5 hours of walking per week.
The results are “encouraging and reassuring for both physicians and patients,” lead author Frederik P.B. Kristensen, MSc, PhD student, department of clinical epidemiology, Aarhus (Denmark) University, said in an interview.
“Our findings are particularly promising for neuropathy since, currently, no disease-modifying treatment exists, and there are limited preventive strategies available.”
Mr. Kristensen highlighted that “most diabetes research has focused on all-cause mortality and macrovascular complications. In the current study, we also found the same pattern for microvascular complications: Even small amounts of physical activity will benefit your health status.”
The minimal level of activity they identified, he said, is also an “achievable [goal] for most type 2 diabetes patients.”
Mr. Kristensen added, however, that the study was limited by excluding individuals with limited mobility and those living in temporary accommodation or care homes.
And prospective studies are required to determine the dose-response relationship between total, not just leisure-time, activity – ideally measured objectively – and risk for microvascular complications, he observed.
The research was published recently in Diabetes Care.
Impact of exercise on microvascular complications in T2D has been uncertain
The authors point out that microvascular complications – such as nerve damage (neuropathy), kidney problems (nephropathy), and eye complications (retinopathy) – occur in more than 50% of individuals with type 2 diabetes and have a “substantial impact” on quality of life, on top of the impact of macrovascular complications (such as cardiovascular disease), disability, and mortality.
Although physical activity is seen as a “cornerstone in the multifactorial management of type 2 diabetes because of its beneficial effects on metabolic risk factors,” the impact on microvascular complications is “uncertain” and the evidence is limited and “conflicting.”
The researchers therefore sought to examine the dose-response association, including the minimal effective level, between leisure-time physical activity and neuropathy, nephropathy, and retinopathy.
They conducted a cohort study of individuals aged 37-82 years from the U.K. Biobank who had type 2 diabetes, which was identified using the Eastwood algorithm and/or an A1c greater than or equal to 48 mmol/mol (6.5%).
Individuals with type 1 diabetes or gestational diabetes were excluded, as were those with major disabling somatic disorders, neurodegenerative diseases, and mental disorders, among others.
Leisure-time physical activity was based on the self-reported frequency, duration, and types of physical activities and was combined to calculate the total leisure time activity in MET-hours per week.
Using the American Diabetes Association/World Health Organization recommendations of 150-300 minutes of moderate to vigorous leisure-time physical activity per week, the researchers determined the recommended moderate activity level to be 150 minutes, (equivalent to 2.5 hours, or 7.5 MET-hours per week).
In all, 18,092 individuals with type 2 diabetes were included in the analysis, of whom 37% were women. The mean age was 60 years.
Ten percent of participants performed no leisure-time physical activity, 38% performed activity below the threshold for moderate activity, 20% performed at the recommended level, and 32% were more active.
Those performing no physical activity were more likely to be women, to be younger, to have a higher body mass index, and to have a greater average A1c, as well as have a more unfavorable sociodemographic and behavioral profile.
Over a median follow-up of 12.1 years, 3.7% of the participants were diagnosed with neuropathy, 10.2% with nephropathy, and 11.7% with retinopathy, equating to an incidence per 1,000 person-years of 3.5, 9,8, and 11.4, respectively.
The researchers found that any level of physical activity was associated with an approximate reduction in the risk for neuropathy and nephropathy.
Multivariate analysis indicated that, compared with no physical activity, activity below the recommended level was associated with an adjusted hazard ratio (aHR) for neuropathy of 0.71, whereas the aHR for activity at the recommended level was 0.73 and that for activity above the recommended level was 0.67.
The aHR for nephropathy, compared with no physical activity, was 0.79 for activity below the recommended level, 0.80 for activity at the recommended level, and 0.80 for activity above the recommended level.
The association between physical activity and retinopathy was weaker, however, at aHRs of 0.91, 0.91, and 0.98 for activity below, at, and above the recommended level, respectively.
The researchers suggest that this lower association could be due to differences in the etiology of the different forms of microvascular complications.
Hyperglycemia is the key driver in the development of retinopathy, they note, whereas other metabolic risk factors, such as obesity, insulin resistance, inflammation, dyslipidemia, and hypertension, play a role in neuropathy and nephropathy.
The associations were also less pronounced in women.
Mr. Kristensen said that this is “an important area that needs to be addressed.”
“While different rates between men and women regarding incidence of type 2 diabetes, metabolic risk factors, complications, and the initiation of, and adherence to, therapy have been found,” he continued, “the exact mechanisms remain unclear. We need a further understanding of sex-differences in metabolic regulation, as well as in material living conditions, social and psychological factors, and access to health care, which may influence the risk of complications.”
Mr. Kristensen added, “Sex differences may be present in more areas than we are aware.”
Mr. Kristensen is supported by a PhD grant from Aarhus University. Other authors received funding from the Danish Diabetes Association, the Australian National Health and Medical Research Council, the New South Wales Government, the Spanish Ministry of Universities, the European Union NextGenerationEU/PRTR (Plan de Recuperación) through a Margarita Salas contract of the University of Vigo, and the Government of Andalusia, Research Talent Recruitment Programme. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
FROM DIABETES CARE
Both too much and not enough sleep raises T2D risk
TOPLINE:
suggests an analysis of a Dutch study.
METHODOLOGY:
- Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
- Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
- Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
- The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.
TAKEAWAY:
- The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
- The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
- In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
- The association between sleep duration and diabetes was not significant.
IN PRACTICE:
The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.
“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
STUDY DETAILS:
The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.
LIMITATIONS:
The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.
DISCLOSURES:
The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
TOPLINE:
suggests an analysis of a Dutch study.
METHODOLOGY:
- Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
- Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
- Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
- The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.
TAKEAWAY:
- The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
- The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
- In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
- The association between sleep duration and diabetes was not significant.
IN PRACTICE:
The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.
“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
STUDY DETAILS:
The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.
LIMITATIONS:
The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.
DISCLOSURES:
The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
TOPLINE:
suggests an analysis of a Dutch study.
METHODOLOGY:
- Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
- Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
- Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
- The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.
TAKEAWAY:
- The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
- The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
- In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
- The association between sleep duration and diabetes was not significant.
IN PRACTICE:
The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.
“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
STUDY DETAILS:
The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.
LIMITATIONS:
The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.
DISCLOSURES:
The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM SLEEP HEALTH
ESC backs SGLT2 inhibitor plus GLP-1 in diabetes with high CVD risk
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AT ESC CONGRESS 2023
Liraglutide fixes learning limit tied to insulin resistance
A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative learning in people with obesity and insulin resistance, a finding that suggests say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative learning about external sensory cues crucially depends on metabolic signaling,” said Marc Tittgemeyer, PhD, professor at the Max Planck Institute for Metabolism Research in Cologne, Germany, and senior author of the study. Study participants with impaired insulin sensitivity “exhibited a reduced amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the starting daily dose for liraglutide for weight loss, available as Saxenda, Novo Nordisk) given the evening before testing.
The findings, from 30 adults with normal insulin sensitivity and normal weight and 24 adults with impaired insulin sensitivity and obesity, suggest that metabolic signals, particularly ones that promote energy restoration in a setting of energy deprivation caused by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly influence neuronal processing,” said Dr. Tittgemeyer. The findings suggest that impaired metabolic signaling such as occurs with insulin resistance in people with obesity can cause deficiencies in associative learning.
‘Liraglutide can normalize learning of associations’
“We show that in people with obesity, disrupted circuit mechanisms lead to impaired learning about sensory associations,” Dr. Tittgemeyer said in an interview. “The information provided by sensory systems that the brain must interpret to select a behavioral response are ‘off tune’ ” in these individuals.
“This is rather consequential for understanding food-intake behaviors. Modern obesity treatments, such as liraglutide, can normalize learning of associations and thereby render people susceptible again for sensory signals and make them more prone to react to subliminal interactions, such as weight-normalizing diets and conscious eating,” he added.
The normalization in associative learning that one dose of liraglutide produced in people with obesity “fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” he explained.
Dr. Tittgemeyer noted that this effect is likely shared by other agents in the GLP-1 receptor agonist class, such as semaglutide (Ozempic, Wegovy, Novo Nordisk) but is likely not an effect when agents agonize receptors to other nutrient-stimulated hormones such as glucagon and the glucose-dependent insulinotropic polypeptide.
The findings “show that liraglutide restores associative learning in participants with greater insulin resistance,” a “highly relevant” discovery, commented Nils B. Kroemer, PhD, head of the section of medical psychology at the University of Bonn, Germany, who was not involved with this research, in a written statement.
The study run by Dr. Tittgemeyer and his associates included 54 healthy adult volunteers whom they assessed for insulin sensitivity with their homeostasis model assessment of insulin resistance. The researchers divided the cohort into groups; one group included 24 people with impaired insulin sensitivity, and one included 30 with normal insulin sensitivity. The average body mass index (BMI) of the normal sensitivity group was about 24 kg/m2; in the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative learning task tested the ability of participants to learn associations between auditory cues (a high or low tone) and a subsequent visual outcome (a picture of a face or a house). During each associative learning session, participants also underwent functional MRI of the brain.
Liraglutide treatment leveled learning
The results showed that the learning rate was significantly lower in the subgroup with impaired insulin sensitivity, compared with those with normal insulin sensitivity following treatment with a placebo injection. This indicates a decreased adaptation of learning to predictability variations in individuals with impaired insulin sensitivity.
In contrast, treatment with a single dose of liraglutide significantly enhanced the learning rate in the group with impaired insulin sensitivity but significantly reduced the learning rate in the group with normal insulin sensitivity. Liraglutide’s effect was twice as large in the group with impaired insulin sensitivity than in the group with normal insulin sensitivity, and these opposing effects of liraglutide resulted in a convergence of the two groups’ adaptive learning rates so that there wasn’t any significant between-group difference following liraglutide treatment.
After analyzing the functional MRI data along with the learning results, the researchers concluded that liraglutide normalized learning in individuals with impaired insulin sensitivity by enhancing adaptive prediction error encoding in the brain’s ventral striatum and mesocortical projection sites.
This apparent ability of GLP-1 analogues to correct this learning deficit in people with impaired insulin sensitivity and obesity has implications regarding potential benefit for people with other pathologies characterized by impaired dopaminergic function and associated with metabolic impairments, such as psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating thing about GLP-1 receptor agonists is that they have an additional mechanism that relates to anti-inflammatory effects, especially for alleviating cell stress,” said Dr. Tittgemeyer. “Many ongoing clinical trials are assessing their effects in neuropsychiatric diseases,” he noted.
The study received no commercial funding. Dr. Tittgemyer and most of his coauthors had no disclosures. One coauthor had several disclosures, which are detailed in the report. Dr. Kroemer had no disclosures.
A version of this article first appeared on Medscape.com.
A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative learning in people with obesity and insulin resistance, a finding that suggests say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative learning about external sensory cues crucially depends on metabolic signaling,” said Marc Tittgemeyer, PhD, professor at the Max Planck Institute for Metabolism Research in Cologne, Germany, and senior author of the study. Study participants with impaired insulin sensitivity “exhibited a reduced amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the starting daily dose for liraglutide for weight loss, available as Saxenda, Novo Nordisk) given the evening before testing.
The findings, from 30 adults with normal insulin sensitivity and normal weight and 24 adults with impaired insulin sensitivity and obesity, suggest that metabolic signals, particularly ones that promote energy restoration in a setting of energy deprivation caused by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly influence neuronal processing,” said Dr. Tittgemeyer. The findings suggest that impaired metabolic signaling such as occurs with insulin resistance in people with obesity can cause deficiencies in associative learning.
‘Liraglutide can normalize learning of associations’
“We show that in people with obesity, disrupted circuit mechanisms lead to impaired learning about sensory associations,” Dr. Tittgemeyer said in an interview. “The information provided by sensory systems that the brain must interpret to select a behavioral response are ‘off tune’ ” in these individuals.
“This is rather consequential for understanding food-intake behaviors. Modern obesity treatments, such as liraglutide, can normalize learning of associations and thereby render people susceptible again for sensory signals and make them more prone to react to subliminal interactions, such as weight-normalizing diets and conscious eating,” he added.
The normalization in associative learning that one dose of liraglutide produced in people with obesity “fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” he explained.
Dr. Tittgemeyer noted that this effect is likely shared by other agents in the GLP-1 receptor agonist class, such as semaglutide (Ozempic, Wegovy, Novo Nordisk) but is likely not an effect when agents agonize receptors to other nutrient-stimulated hormones such as glucagon and the glucose-dependent insulinotropic polypeptide.
The findings “show that liraglutide restores associative learning in participants with greater insulin resistance,” a “highly relevant” discovery, commented Nils B. Kroemer, PhD, head of the section of medical psychology at the University of Bonn, Germany, who was not involved with this research, in a written statement.
The study run by Dr. Tittgemeyer and his associates included 54 healthy adult volunteers whom they assessed for insulin sensitivity with their homeostasis model assessment of insulin resistance. The researchers divided the cohort into groups; one group included 24 people with impaired insulin sensitivity, and one included 30 with normal insulin sensitivity. The average body mass index (BMI) of the normal sensitivity group was about 24 kg/m2; in the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative learning task tested the ability of participants to learn associations between auditory cues (a high or low tone) and a subsequent visual outcome (a picture of a face or a house). During each associative learning session, participants also underwent functional MRI of the brain.
Liraglutide treatment leveled learning
The results showed that the learning rate was significantly lower in the subgroup with impaired insulin sensitivity, compared with those with normal insulin sensitivity following treatment with a placebo injection. This indicates a decreased adaptation of learning to predictability variations in individuals with impaired insulin sensitivity.
In contrast, treatment with a single dose of liraglutide significantly enhanced the learning rate in the group with impaired insulin sensitivity but significantly reduced the learning rate in the group with normal insulin sensitivity. Liraglutide’s effect was twice as large in the group with impaired insulin sensitivity than in the group with normal insulin sensitivity, and these opposing effects of liraglutide resulted in a convergence of the two groups’ adaptive learning rates so that there wasn’t any significant between-group difference following liraglutide treatment.
After analyzing the functional MRI data along with the learning results, the researchers concluded that liraglutide normalized learning in individuals with impaired insulin sensitivity by enhancing adaptive prediction error encoding in the brain’s ventral striatum and mesocortical projection sites.
This apparent ability of GLP-1 analogues to correct this learning deficit in people with impaired insulin sensitivity and obesity has implications regarding potential benefit for people with other pathologies characterized by impaired dopaminergic function and associated with metabolic impairments, such as psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating thing about GLP-1 receptor agonists is that they have an additional mechanism that relates to anti-inflammatory effects, especially for alleviating cell stress,” said Dr. Tittgemeyer. “Many ongoing clinical trials are assessing their effects in neuropsychiatric diseases,” he noted.
The study received no commercial funding. Dr. Tittgemyer and most of his coauthors had no disclosures. One coauthor had several disclosures, which are detailed in the report. Dr. Kroemer had no disclosures.
A version of this article first appeared on Medscape.com.
A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative learning in people with obesity and insulin resistance, a finding that suggests say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative learning about external sensory cues crucially depends on metabolic signaling,” said Marc Tittgemeyer, PhD, professor at the Max Planck Institute for Metabolism Research in Cologne, Germany, and senior author of the study. Study participants with impaired insulin sensitivity “exhibited a reduced amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the starting daily dose for liraglutide for weight loss, available as Saxenda, Novo Nordisk) given the evening before testing.
The findings, from 30 adults with normal insulin sensitivity and normal weight and 24 adults with impaired insulin sensitivity and obesity, suggest that metabolic signals, particularly ones that promote energy restoration in a setting of energy deprivation caused by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly influence neuronal processing,” said Dr. Tittgemeyer. The findings suggest that impaired metabolic signaling such as occurs with insulin resistance in people with obesity can cause deficiencies in associative learning.
‘Liraglutide can normalize learning of associations’
“We show that in people with obesity, disrupted circuit mechanisms lead to impaired learning about sensory associations,” Dr. Tittgemeyer said in an interview. “The information provided by sensory systems that the brain must interpret to select a behavioral response are ‘off tune’ ” in these individuals.
“This is rather consequential for understanding food-intake behaviors. Modern obesity treatments, such as liraglutide, can normalize learning of associations and thereby render people susceptible again for sensory signals and make them more prone to react to subliminal interactions, such as weight-normalizing diets and conscious eating,” he added.
The normalization in associative learning that one dose of liraglutide produced in people with obesity “fits with studies showing that these drugs restore a normal feeling of satiety, causing people to eat less and therefore lose weight,” he explained.
Dr. Tittgemeyer noted that this effect is likely shared by other agents in the GLP-1 receptor agonist class, such as semaglutide (Ozempic, Wegovy, Novo Nordisk) but is likely not an effect when agents agonize receptors to other nutrient-stimulated hormones such as glucagon and the glucose-dependent insulinotropic polypeptide.
The findings “show that liraglutide restores associative learning in participants with greater insulin resistance,” a “highly relevant” discovery, commented Nils B. Kroemer, PhD, head of the section of medical psychology at the University of Bonn, Germany, who was not involved with this research, in a written statement.
The study run by Dr. Tittgemeyer and his associates included 54 healthy adult volunteers whom they assessed for insulin sensitivity with their homeostasis model assessment of insulin resistance. The researchers divided the cohort into groups; one group included 24 people with impaired insulin sensitivity, and one included 30 with normal insulin sensitivity. The average body mass index (BMI) of the normal sensitivity group was about 24 kg/m2; in the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative learning task tested the ability of participants to learn associations between auditory cues (a high or low tone) and a subsequent visual outcome (a picture of a face or a house). During each associative learning session, participants also underwent functional MRI of the brain.
Liraglutide treatment leveled learning
The results showed that the learning rate was significantly lower in the subgroup with impaired insulin sensitivity, compared with those with normal insulin sensitivity following treatment with a placebo injection. This indicates a decreased adaptation of learning to predictability variations in individuals with impaired insulin sensitivity.
In contrast, treatment with a single dose of liraglutide significantly enhanced the learning rate in the group with impaired insulin sensitivity but significantly reduced the learning rate in the group with normal insulin sensitivity. Liraglutide’s effect was twice as large in the group with impaired insulin sensitivity than in the group with normal insulin sensitivity, and these opposing effects of liraglutide resulted in a convergence of the two groups’ adaptive learning rates so that there wasn’t any significant between-group difference following liraglutide treatment.
After analyzing the functional MRI data along with the learning results, the researchers concluded that liraglutide normalized learning in individuals with impaired insulin sensitivity by enhancing adaptive prediction error encoding in the brain’s ventral striatum and mesocortical projection sites.
This apparent ability of GLP-1 analogues to correct this learning deficit in people with impaired insulin sensitivity and obesity has implications regarding potential benefit for people with other pathologies characterized by impaired dopaminergic function and associated with metabolic impairments, such as psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating thing about GLP-1 receptor agonists is that they have an additional mechanism that relates to anti-inflammatory effects, especially for alleviating cell stress,” said Dr. Tittgemeyer. “Many ongoing clinical trials are assessing their effects in neuropsychiatric diseases,” he noted.
The study received no commercial funding. Dr. Tittgemyer and most of his coauthors had no disclosures. One coauthor had several disclosures, which are detailed in the report. Dr. Kroemer had no disclosures.
A version of this article first appeared on Medscape.com.
FROM NATURE METABOLISM