Diabetes

Would closed-loop systems be a good option for young patients with type 1 diabetes?

International and French recommendations on closed-loop systems state that the use of an “artificial pancreas” should be reserved for adults who are fully engaged with their treatment. This means that young patients, especially adolescents, who are less likely to comply with treatment and are more likely to experience suboptimal blood glucose control, are often excluded from the use of such systems for managing their diabetes.

Several recent studies seem to call this approach into question.

One such study, which was presented at a Francophone Diabetes Society conference and was published in Nature Communications, showed that adolescents with poorly controlled diabetes who were equipped with closed-loop systems gained IQ points and reasoning capacity and experienced a reduction in edematous tissue in the brain cortex. Furthermore, with the closed-loop system, patients spent 13% more time in a target range, and there was a significant reduction in time spent in hyperglycemia.

In the same vein, a small prospective study published in Diabetes Care showed that the closed-loop system with the Minimed 780G pump improved glycemic control for 20 young patients with type 1 diabetes aged 13-25 years whose diabetes was poorly controlled (hemoglobin A1c ≥ 8.5%). At the end of the 3-month study period, the average A1c had decreased from 10.5% (±2.1%) to 7.6% (±1.1%), an average decrease of 2.9%. The time spent in target A1c, which was set from 0.70 g/L to 1.80 g/L, was increased by almost 40%.

With respect to very young children, a study published in The New England Journal of Medicine also showed a favorable risk-benefit ratio for closed-loop systems. The trial, which enrolled 102 children aged 2 years to less than 6 years who had type 1 diabetes, showed that the amount of time that the glucose level was within the target range during the 13-week study period was higher (+3 hours) for those who had been randomly assigned to receive the hybrid closed-loop system (n = 68) than for those who had received the standard treatment (n = 34), either with an insulin pump or multiple daily injections or a Dexcom G6 continuous glucose monitoring device.

A previous study carried out by the Paris Public Hospital System had already shown that the French Diabeloop system could reduce episodes of hypoglycemia and achieve good glycemic control for prepubescent children (n = 21; aged 6-12 years) with type 1 diabetes in real-life conditions.

Eric Renard, MD, PhD, head of the department of endocrinology and diabetes at Lapeyronie Hospital in Montpellier, France, was not surprised at the findings from the study, especially in adolescents with poorly controlled diabetes.

“We have already seen studies in which those patients who had the most poorly controlled diabetes at the start were the ones who improved the most with the closed-loop system, by at least 20% in terms of time in target. These findings resonate with what I see in my clinic,” said Dr. Renard in an interview.

“In my experience, these young adolescents, who neglected their diabetes when they had no devices to help control it, when they had to inject themselves, et cetera ... well, they’re just not the same people when they’re put on a closed-loop system,” he added. “They rise to the challenge, and for the first time, they succeed without making a huge effort, since the algorithm does what they weren’t doing. It’s astonishing to see near-total engagement in these young people when explaining the technology to them and saying, ‘Let’s give it a go.’ These are the very same youngsters who didn’t want to hear about their diabetes in the past. They are delighted and once again involved in managing their condition.”

That’s why Dr. Renard recommends keeping an open mind when considering treatment options for young patients with poorly controlled type 1 diabetes.

“When young people have very poorly controlled diabetes, they risk having cardiovascular complications and damaging their retinas and kidneys,” he said. “If we can get them from 25% to 45% time in target, even if that hasn’t been easy to achieve, this will help save their blood vessels! The only thing we have to be careful of is that we don’t set up a closed-loop system in someone who doesn’t want one. But, if it can manage to spark the interest of a young patient, in most cases, it’s beneficial.”

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

Would closed-loop systems be a good option for young patients with type 1 diabetes?

International and French recommendations on closed-loop systems state that the use of an “artificial pancreas” should be reserved for adults who are fully engaged with their treatment. This means that young patients, especially adolescents, who are less likely to comply with treatment and are more likely to experience suboptimal blood glucose control, are often excluded from the use of such systems for managing their diabetes.

Several recent studies seem to call this approach into question.

One such study, which was presented at a Francophone Diabetes Society conference and was published in Nature Communications, showed that adolescents with poorly controlled diabetes who were equipped with closed-loop systems gained IQ points and reasoning capacity and experienced a reduction in edematous tissue in the brain cortex. Furthermore, with the closed-loop system, patients spent 13% more time in a target range, and there was a significant reduction in time spent in hyperglycemia.

In the same vein, a small prospective study published in Diabetes Care showed that the closed-loop system with the Minimed 780G pump improved glycemic control for 20 young patients with type 1 diabetes aged 13-25 years whose diabetes was poorly controlled (hemoglobin A1c ≥ 8.5%). At the end of the 3-month study period, the average A1c had decreased from 10.5% (±2.1%) to 7.6% (±1.1%), an average decrease of 2.9%. The time spent in target A1c, which was set from 0.70 g/L to 1.80 g/L, was increased by almost 40%.

With respect to very young children, a study published in The New England Journal of Medicine also showed a favorable risk-benefit ratio for closed-loop systems. The trial, which enrolled 102 children aged 2 years to less than 6 years who had type 1 diabetes, showed that the amount of time that the glucose level was within the target range during the 13-week study period was higher (+3 hours) for those who had been randomly assigned to receive the hybrid closed-loop system (n = 68) than for those who had received the standard treatment (n = 34), either with an insulin pump or multiple daily injections or a Dexcom G6 continuous glucose monitoring device.

A previous study carried out by the Paris Public Hospital System had already shown that the French Diabeloop system could reduce episodes of hypoglycemia and achieve good glycemic control for prepubescent children (n = 21; aged 6-12 years) with type 1 diabetes in real-life conditions.

Eric Renard, MD, PhD, head of the department of endocrinology and diabetes at Lapeyronie Hospital in Montpellier, France, was not surprised at the findings from the study, especially in adolescents with poorly controlled diabetes.

“We have already seen studies in which those patients who had the most poorly controlled diabetes at the start were the ones who improved the most with the closed-loop system, by at least 20% in terms of time in target. These findings resonate with what I see in my clinic,” said Dr. Renard in an interview.

“In my experience, these young adolescents, who neglected their diabetes when they had no devices to help control it, when they had to inject themselves, et cetera ... well, they’re just not the same people when they’re put on a closed-loop system,” he added. “They rise to the challenge, and for the first time, they succeed without making a huge effort, since the algorithm does what they weren’t doing. It’s astonishing to see near-total engagement in these young people when explaining the technology to them and saying, ‘Let’s give it a go.’ These are the very same youngsters who didn’t want to hear about their diabetes in the past. They are delighted and once again involved in managing their condition.”

That’s why Dr. Renard recommends keeping an open mind when considering treatment options for young patients with poorly controlled type 1 diabetes.

“When young people have very poorly controlled diabetes, they risk having cardiovascular complications and damaging their retinas and kidneys,” he said. “If we can get them from 25% to 45% time in target, even if that hasn’t been easy to achieve, this will help save their blood vessels! The only thing we have to be careful of is that we don’t set up a closed-loop system in someone who doesn’t want one. But, if it can manage to spark the interest of a young patient, in most cases, it’s beneficial.”

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

Would closed-loop systems be a good option for young patients with type 1 diabetes?

International and French recommendations on closed-loop systems state that the use of an “artificial pancreas” should be reserved for adults who are fully engaged with their treatment. This means that young patients, especially adolescents, who are less likely to comply with treatment and are more likely to experience suboptimal blood glucose control, are often excluded from the use of such systems for managing their diabetes.

Several recent studies seem to call this approach into question.

One such study, which was presented at a Francophone Diabetes Society conference and was published in Nature Communications, showed that adolescents with poorly controlled diabetes who were equipped with closed-loop systems gained IQ points and reasoning capacity and experienced a reduction in edematous tissue in the brain cortex. Furthermore, with the closed-loop system, patients spent 13% more time in a target range, and there was a significant reduction in time spent in hyperglycemia.

In the same vein, a small prospective study published in Diabetes Care showed that the closed-loop system with the Minimed 780G pump improved glycemic control for 20 young patients with type 1 diabetes aged 13-25 years whose diabetes was poorly controlled (hemoglobin A1c ≥ 8.5%). At the end of the 3-month study period, the average A1c had decreased from 10.5% (±2.1%) to 7.6% (±1.1%), an average decrease of 2.9%. The time spent in target A1c, which was set from 0.70 g/L to 1.80 g/L, was increased by almost 40%.

With respect to very young children, a study published in The New England Journal of Medicine also showed a favorable risk-benefit ratio for closed-loop systems. The trial, which enrolled 102 children aged 2 years to less than 6 years who had type 1 diabetes, showed that the amount of time that the glucose level was within the target range during the 13-week study period was higher (+3 hours) for those who had been randomly assigned to receive the hybrid closed-loop system (n = 68) than for those who had received the standard treatment (n = 34), either with an insulin pump or multiple daily injections or a Dexcom G6 continuous glucose monitoring device.

A previous study carried out by the Paris Public Hospital System had already shown that the French Diabeloop system could reduce episodes of hypoglycemia and achieve good glycemic control for prepubescent children (n = 21; aged 6-12 years) with type 1 diabetes in real-life conditions.

Eric Renard, MD, PhD, head of the department of endocrinology and diabetes at Lapeyronie Hospital in Montpellier, France, was not surprised at the findings from the study, especially in adolescents with poorly controlled diabetes.

“We have already seen studies in which those patients who had the most poorly controlled diabetes at the start were the ones who improved the most with the closed-loop system, by at least 20% in terms of time in target. These findings resonate with what I see in my clinic,” said Dr. Renard in an interview.

“In my experience, these young adolescents, who neglected their diabetes when they had no devices to help control it, when they had to inject themselves, et cetera ... well, they’re just not the same people when they’re put on a closed-loop system,” he added. “They rise to the challenge, and for the first time, they succeed without making a huge effort, since the algorithm does what they weren’t doing. It’s astonishing to see near-total engagement in these young people when explaining the technology to them and saying, ‘Let’s give it a go.’ These are the very same youngsters who didn’t want to hear about their diabetes in the past. They are delighted and once again involved in managing their condition.”

That’s why Dr. Renard recommends keeping an open mind when considering treatment options for young patients with poorly controlled type 1 diabetes.

“When young people have very poorly controlled diabetes, they risk having cardiovascular complications and damaging their retinas and kidneys,” he said. “If we can get them from 25% to 45% time in target, even if that hasn’t been easy to achieve, this will help save their blood vessels! The only thing we have to be careful of is that we don’t set up a closed-loop system in someone who doesn’t want one. But, if it can manage to spark the interest of a young patient, in most cases, it’s beneficial.”

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

The lowest available national prices of drugs to treat obesity are up to 20 times higher than the estimated cost of profitable generic versions of the same agents, according to a new analysis.
 

The findings by Jacob Levi, MBBS, and colleagues were published in Obesity.

“Our study highlights the inequality in pricing that exists for effective antiobesity medications, which are largely unaffordable in most countries,” Dr. Levi, from Royal Free Hospital NHS Trust, London, said in a press release.

“We show that these drugs can actually be produced and sold profitably for low prices,” he summarized. “A public health approach that prioritizes improving access to medications should be adopted, instead of allowing companies to maximize profits,” Dr. Levi urged.

Dr. Levi and colleagues studied the oral agents orlistat, naltrexone/bupropion, topiramate/phentermine, and semaglutide, and subcutaneous liraglutide, semaglutide, and tirzepatide (all approved by the U.S. Food and Drug Administration to treat obesity, except for oral semaglutide and subcutaneous tirzepatide, which are not yet approved to treat obesity in the absence of type 2 diabetes).

“Worldwide, more people are dying from diabetes and clinical obesity than HIV, tuberculosis, and malaria combined now,” senior author Andrew Hill, MD, department of pharmacology and therapeutics, University of Liverpool, England, pointed out.
 

We need to repeat the low-cost success story with obesity drugs

“Millions of lives have been saved by treating infectious diseases at low cost in poor countries,” Dr. Hill continued. “Now we need to repeat this medical success story, with mass treatment of diabetes and clinical obesity at low prices.”

However, in an accompanying editorial, Eric A. Finkelstein, MD, and Junxing Chay, PhD, Duke-NUS Medical School, Singapore, maintain that “It would be great if everyone had affordable access to all medicines that might improve their health. Yet that is simply not possible, nor will it ever be.”

“What is truly needed is a better way to ration the health care dollars currently available in efforts to maximize population health. That is the challenge ahead not just for [antiobesity medications] but for all treatments,” they say.

“Greater use of cost-effectiveness analysis and direct negotiations, while maintaining the patent system, represents an appropriate approach for allocating scarce health care resources in the United States and beyond,” they continue.
 

Lowest current patented drug prices vs. estimated generic drug prices

New medications for obesity were highly effective in recent clinical trials, but high prices limit the ability of patients to get these medications, Dr. Levi and colleagues write.

They analyzed prices for obesity drugs in 16 low-, middle-, and high-income countries: Australia, Bangladesh, China, France, Germany, India, Kenya, Morocco, Norway, Peru, Pakistan, South Africa, Turkey, the United Kingdom, the United States, and Vietnam.

The researchers assessed the price of a 30-day supply of each of the studied branded drugs based on the lowest available price (in 2021 U.S. dollars) from multiple online national price databases.

Then they calculated the estimated minimum price of a 30-day supply of a potential generic version of these drugs, which included the cost of the active medicinal ingredients, the excipients (nonactive ingredients), the prefilled injectable device plus needles (for subcutaneous drugs), transportation, 10% profit, and 27% tax on profit.

The national prices of the branded medications for obesity were significantly higher than the estimated minimum prices of potential generic drugs (see Table).

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

The lowest available national prices of drugs to treat obesity are up to 20 times higher than the estimated cost of profitable generic versions of the same agents, according to a new analysis.
 

The findings by Jacob Levi, MBBS, and colleagues were published in Obesity.

“Our study highlights the inequality in pricing that exists for effective antiobesity medications, which are largely unaffordable in most countries,” Dr. Levi, from Royal Free Hospital NHS Trust, London, said in a press release.

“We show that these drugs can actually be produced and sold profitably for low prices,” he summarized. “A public health approach that prioritizes improving access to medications should be adopted, instead of allowing companies to maximize profits,” Dr. Levi urged.

Dr. Levi and colleagues studied the oral agents orlistat, naltrexone/bupropion, topiramate/phentermine, and semaglutide, and subcutaneous liraglutide, semaglutide, and tirzepatide (all approved by the U.S. Food and Drug Administration to treat obesity, except for oral semaglutide and subcutaneous tirzepatide, which are not yet approved to treat obesity in the absence of type 2 diabetes).

“Worldwide, more people are dying from diabetes and clinical obesity than HIV, tuberculosis, and malaria combined now,” senior author Andrew Hill, MD, department of pharmacology and therapeutics, University of Liverpool, England, pointed out.
 

We need to repeat the low-cost success story with obesity drugs

“Millions of lives have been saved by treating infectious diseases at low cost in poor countries,” Dr. Hill continued. “Now we need to repeat this medical success story, with mass treatment of diabetes and clinical obesity at low prices.”

However, in an accompanying editorial, Eric A. Finkelstein, MD, and Junxing Chay, PhD, Duke-NUS Medical School, Singapore, maintain that “It would be great if everyone had affordable access to all medicines that might improve their health. Yet that is simply not possible, nor will it ever be.”

“What is truly needed is a better way to ration the health care dollars currently available in efforts to maximize population health. That is the challenge ahead not just for [antiobesity medications] but for all treatments,” they say.

“Greater use of cost-effectiveness analysis and direct negotiations, while maintaining the patent system, represents an appropriate approach for allocating scarce health care resources in the United States and beyond,” they continue.
 

Lowest current patented drug prices vs. estimated generic drug prices

New medications for obesity were highly effective in recent clinical trials, but high prices limit the ability of patients to get these medications, Dr. Levi and colleagues write.

They analyzed prices for obesity drugs in 16 low-, middle-, and high-income countries: Australia, Bangladesh, China, France, Germany, India, Kenya, Morocco, Norway, Peru, Pakistan, South Africa, Turkey, the United Kingdom, the United States, and Vietnam.

The researchers assessed the price of a 30-day supply of each of the studied branded drugs based on the lowest available price (in 2021 U.S. dollars) from multiple online national price databases.

Then they calculated the estimated minimum price of a 30-day supply of a potential generic version of these drugs, which included the cost of the active medicinal ingredients, the excipients (nonactive ingredients), the prefilled injectable device plus needles (for subcutaneous drugs), transportation, 10% profit, and 27% tax on profit.

The national prices of the branded medications for obesity were significantly higher than the estimated minimum prices of potential generic drugs (see Table).

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

The lowest available national prices of drugs to treat obesity are up to 20 times higher than the estimated cost of profitable generic versions of the same agents, according to a new analysis.
 

The findings by Jacob Levi, MBBS, and colleagues were published in Obesity.

“Our study highlights the inequality in pricing that exists for effective antiobesity medications, which are largely unaffordable in most countries,” Dr. Levi, from Royal Free Hospital NHS Trust, London, said in a press release.

“We show that these drugs can actually be produced and sold profitably for low prices,” he summarized. “A public health approach that prioritizes improving access to medications should be adopted, instead of allowing companies to maximize profits,” Dr. Levi urged.

Dr. Levi and colleagues studied the oral agents orlistat, naltrexone/bupropion, topiramate/phentermine, and semaglutide, and subcutaneous liraglutide, semaglutide, and tirzepatide (all approved by the U.S. Food and Drug Administration to treat obesity, except for oral semaglutide and subcutaneous tirzepatide, which are not yet approved to treat obesity in the absence of type 2 diabetes).

“Worldwide, more people are dying from diabetes and clinical obesity than HIV, tuberculosis, and malaria combined now,” senior author Andrew Hill, MD, department of pharmacology and therapeutics, University of Liverpool, England, pointed out.
 

We need to repeat the low-cost success story with obesity drugs

“Millions of lives have been saved by treating infectious diseases at low cost in poor countries,” Dr. Hill continued. “Now we need to repeat this medical success story, with mass treatment of diabetes and clinical obesity at low prices.”

However, in an accompanying editorial, Eric A. Finkelstein, MD, and Junxing Chay, PhD, Duke-NUS Medical School, Singapore, maintain that “It would be great if everyone had affordable access to all medicines that might improve their health. Yet that is simply not possible, nor will it ever be.”

“What is truly needed is a better way to ration the health care dollars currently available in efforts to maximize population health. That is the challenge ahead not just for [antiobesity medications] but for all treatments,” they say.

“Greater use of cost-effectiveness analysis and direct negotiations, while maintaining the patent system, represents an appropriate approach for allocating scarce health care resources in the United States and beyond,” they continue.
 

Lowest current patented drug prices vs. estimated generic drug prices

New medications for obesity were highly effective in recent clinical trials, but high prices limit the ability of patients to get these medications, Dr. Levi and colleagues write.

They analyzed prices for obesity drugs in 16 low-, middle-, and high-income countries: Australia, Bangladesh, China, France, Germany, India, Kenya, Morocco, Norway, Peru, Pakistan, South Africa, Turkey, the United Kingdom, the United States, and Vietnam.

The researchers assessed the price of a 30-day supply of each of the studied branded drugs based on the lowest available price (in 2021 U.S. dollars) from multiple online national price databases.

Then they calculated the estimated minimum price of a 30-day supply of a potential generic version of these drugs, which included the cost of the active medicinal ingredients, the excipients (nonactive ingredients), the prefilled injectable device plus needles (for subcutaneous drugs), transportation, 10% profit, and 27% tax on profit.

The national prices of the branded medications for obesity were significantly higher than the estimated minimum prices of potential generic drugs (see Table).

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

The “twincretin” tirzepatide (Mounjaro) has proven successful in SURMOUNT-2, the second pivotal trial for the drug as an antiobesity agent, according to top-line results reported April 27 by tirzepatide’s manufacturer, Lilly, in a press release. The company reveals that tirzepatide achieved both of its primary endpoints in the trial, as well as all its key secondary endpoints.

The findings pave the way for tirzepatide to likely receive Food and Drug Administration approval as a treatment for obesity, perhaps before the end of 2023.

Tirzepatide received FDA approval in May 2022 for the treatment of type 2 diabetes in adults, under the brand name Mounjaro, and some people have already been using it off-label to treat obesity.

Tirzepatide is a dual glucagonlike peptide–1 (GLP-1) agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, a once-weekly injection, which is approved as Wegovy for patients with obesity and as Ozempic for treatment of type 2 diabetes.

These agents have been incredibly popular among celebrity influencers, and with use of the #Ozempic hashtag and others on social media, this has led to unprecedented use of these products for weight loss, often among those who do not even have obesity or type 2 diabetes. Subsequently, patients with type 2 diabetes and obesity who need them have often struggled to obtain them, owing to shortages following this phenomenon.
 

SURMOUNT-2: Weight loss around 15%, less than seen in SURMOUNT-1

SURMOUNT-2 enrolled 938 adults with overweight or obesity and type 2 diabetes and had dual primary endpoints that both focused on weight loss, compared with placebo.

The first completed pivotal trial of tirzepatide for weight loss, SURMOUNT-1, enrolled people with overweight or obesity but no diabetes and had its main results reported in 2022. At the time, the weight loss achieved with tirzepatide, was described as “unprecedented,” with those given the highest dose in that trial (15 mg subcutaneously per week) losing an average of 20%-22% of body weight over 72 weeks, depending on the specific statistical analysis used.

For SURMOUNT-2’s first primary endpoint, 72 weeks of weekly subcutaneous injections with tirzepatide at dosages of 10 mg or 15 mg led to an average weight loss from baseline of 13.4% and 15.7%, respectively, compared with an average loss of 3.3% from baseline in the placebo-treated control arm.

For the second primary endpoint, 81.6% of people on the 10-mg dose and 86.4% on the 15-mg dose achieved at least 5% weight loss from baseline, compared with 30.5% of controls who had at least 5% weight loss from baseline.

In one key secondary endpoint, tirzepatide at dosages of 10 mg or 15 mg weekly produced at least a 15% cut in weight from baseline in 41.4% and 51.8% of participants, respectively, compared with a 2.6% rate of this endpoint in the placebo controls.

So the extent of weight loss seen in in SURMOUNT-2 was somewhat less than was reported in SURMOUNT-1, a finding consistent with many prior studies of incretin-based weight-loss agents, which seem to pack a more potent weight-loss punch in people without type 2 diabetes.

Lilly did not specifically report the treatment effect of tirzepatide on hemoglobin A1c in SURMOUNT-2, only saying that the effect was similar to what had been seen in the series of five SURPASS trials that led to the approval of tirzepatide for type 2 diabetes.

Lilly also reported that the safety profile of tirzepatide in SURMOUNT-2 generally matched what was seen in SURMOUNT-1 as well as in the SURPASS trials. The most common adverse events in SURMOUNT-2 involved gastrointestinal symptoms, such as nausea, diarrhea, and vomiting; these were generally mild to moderate in severity and clustered during the dose-escalation phase at the start of treatment. Treatment discontinuations caused by adverse effects were 3.8% on the 10-mg dosage, 7.4% on the 15-mg dosage, and 3.8% on placebo.

SURMOUNT-2 enrolled patients in the United States, Puerto Rico, and five other countries. All participants also received interventions designed to reduce their calorie intake and increase their physical activity.
 

More SURMOUNT-2 results at ADA in June

Lilly also announced that researchers would report more complete results from SURMOUNT-2 at the 2023 scientific sessions of the American Diabetes Association, being held in San Diego in late June, and publish the findings in a major medical journal.

Results from two additional phase 3 trials of tirzepatide in people with overweight or obesity, SURMOUNT-3 and SURMOUNT-4, are expected later in 2023.

Lilly started an application to the FDA for an indication for weight loss in October 2022 under a fast track designation by the agency, and the data collected in SURMOUNT-2 are expected to complete this application, which would then be subject to an FDA decision within about 6 months. Lilly said in its April 27 press release that it anticipates an FDA decision on this application may occur before the end of 2023.

SURMOUNT-2 and all of the other tirzepatide trials were sponsored by Lilly.

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

The “twincretin” tirzepatide (Mounjaro) has proven successful in SURMOUNT-2, the second pivotal trial for the drug as an antiobesity agent, according to top-line results reported April 27 by tirzepatide’s manufacturer, Lilly, in a press release. The company reveals that tirzepatide achieved both of its primary endpoints in the trial, as well as all its key secondary endpoints.

The findings pave the way for tirzepatide to likely receive Food and Drug Administration approval as a treatment for obesity, perhaps before the end of 2023.

Tirzepatide received FDA approval in May 2022 for the treatment of type 2 diabetes in adults, under the brand name Mounjaro, and some people have already been using it off-label to treat obesity.

Tirzepatide is a dual glucagonlike peptide–1 (GLP-1) agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, a once-weekly injection, which is approved as Wegovy for patients with obesity and as Ozempic for treatment of type 2 diabetes.

These agents have been incredibly popular among celebrity influencers, and with use of the #Ozempic hashtag and others on social media, this has led to unprecedented use of these products for weight loss, often among those who do not even have obesity or type 2 diabetes. Subsequently, patients with type 2 diabetes and obesity who need them have often struggled to obtain them, owing to shortages following this phenomenon.
 

SURMOUNT-2: Weight loss around 15%, less than seen in SURMOUNT-1

SURMOUNT-2 enrolled 938 adults with overweight or obesity and type 2 diabetes and had dual primary endpoints that both focused on weight loss, compared with placebo.

The first completed pivotal trial of tirzepatide for weight loss, SURMOUNT-1, enrolled people with overweight or obesity but no diabetes and had its main results reported in 2022. At the time, the weight loss achieved with tirzepatide, was described as “unprecedented,” with those given the highest dose in that trial (15 mg subcutaneously per week) losing an average of 20%-22% of body weight over 72 weeks, depending on the specific statistical analysis used.

For SURMOUNT-2’s first primary endpoint, 72 weeks of weekly subcutaneous injections with tirzepatide at dosages of 10 mg or 15 mg led to an average weight loss from baseline of 13.4% and 15.7%, respectively, compared with an average loss of 3.3% from baseline in the placebo-treated control arm.

For the second primary endpoint, 81.6% of people on the 10-mg dose and 86.4% on the 15-mg dose achieved at least 5% weight loss from baseline, compared with 30.5% of controls who had at least 5% weight loss from baseline.

In one key secondary endpoint, tirzepatide at dosages of 10 mg or 15 mg weekly produced at least a 15% cut in weight from baseline in 41.4% and 51.8% of participants, respectively, compared with a 2.6% rate of this endpoint in the placebo controls.

So the extent of weight loss seen in in SURMOUNT-2 was somewhat less than was reported in SURMOUNT-1, a finding consistent with many prior studies of incretin-based weight-loss agents, which seem to pack a more potent weight-loss punch in people without type 2 diabetes.

Lilly did not specifically report the treatment effect of tirzepatide on hemoglobin A1c in SURMOUNT-2, only saying that the effect was similar to what had been seen in the series of five SURPASS trials that led to the approval of tirzepatide for type 2 diabetes.

Lilly also reported that the safety profile of tirzepatide in SURMOUNT-2 generally matched what was seen in SURMOUNT-1 as well as in the SURPASS trials. The most common adverse events in SURMOUNT-2 involved gastrointestinal symptoms, such as nausea, diarrhea, and vomiting; these were generally mild to moderate in severity and clustered during the dose-escalation phase at the start of treatment. Treatment discontinuations caused by adverse effects were 3.8% on the 10-mg dosage, 7.4% on the 15-mg dosage, and 3.8% on placebo.

SURMOUNT-2 enrolled patients in the United States, Puerto Rico, and five other countries. All participants also received interventions designed to reduce their calorie intake and increase their physical activity.
 

More SURMOUNT-2 results at ADA in June

Lilly also announced that researchers would report more complete results from SURMOUNT-2 at the 2023 scientific sessions of the American Diabetes Association, being held in San Diego in late June, and publish the findings in a major medical journal.

Results from two additional phase 3 trials of tirzepatide in people with overweight or obesity, SURMOUNT-3 and SURMOUNT-4, are expected later in 2023.

Lilly started an application to the FDA for an indication for weight loss in October 2022 under a fast track designation by the agency, and the data collected in SURMOUNT-2 are expected to complete this application, which would then be subject to an FDA decision within about 6 months. Lilly said in its April 27 press release that it anticipates an FDA decision on this application may occur before the end of 2023.

SURMOUNT-2 and all of the other tirzepatide trials were sponsored by Lilly.

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

The “twincretin” tirzepatide (Mounjaro) has proven successful in SURMOUNT-2, the second pivotal trial for the drug as an antiobesity agent, according to top-line results reported April 27 by tirzepatide’s manufacturer, Lilly, in a press release. The company reveals that tirzepatide achieved both of its primary endpoints in the trial, as well as all its key secondary endpoints.

The findings pave the way for tirzepatide to likely receive Food and Drug Administration approval as a treatment for obesity, perhaps before the end of 2023.

Tirzepatide received FDA approval in May 2022 for the treatment of type 2 diabetes in adults, under the brand name Mounjaro, and some people have already been using it off-label to treat obesity.

Tirzepatide is a dual glucagonlike peptide–1 (GLP-1) agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, a once-weekly injection, which is approved as Wegovy for patients with obesity and as Ozempic for treatment of type 2 diabetes.

These agents have been incredibly popular among celebrity influencers, and with use of the #Ozempic hashtag and others on social media, this has led to unprecedented use of these products for weight loss, often among those who do not even have obesity or type 2 diabetes. Subsequently, patients with type 2 diabetes and obesity who need them have often struggled to obtain them, owing to shortages following this phenomenon.
 

SURMOUNT-2: Weight loss around 15%, less than seen in SURMOUNT-1

SURMOUNT-2 enrolled 938 adults with overweight or obesity and type 2 diabetes and had dual primary endpoints that both focused on weight loss, compared with placebo.

The first completed pivotal trial of tirzepatide for weight loss, SURMOUNT-1, enrolled people with overweight or obesity but no diabetes and had its main results reported in 2022. At the time, the weight loss achieved with tirzepatide, was described as “unprecedented,” with those given the highest dose in that trial (15 mg subcutaneously per week) losing an average of 20%-22% of body weight over 72 weeks, depending on the specific statistical analysis used.

For SURMOUNT-2’s first primary endpoint, 72 weeks of weekly subcutaneous injections with tirzepatide at dosages of 10 mg or 15 mg led to an average weight loss from baseline of 13.4% and 15.7%, respectively, compared with an average loss of 3.3% from baseline in the placebo-treated control arm.

For the second primary endpoint, 81.6% of people on the 10-mg dose and 86.4% on the 15-mg dose achieved at least 5% weight loss from baseline, compared with 30.5% of controls who had at least 5% weight loss from baseline.

In one key secondary endpoint, tirzepatide at dosages of 10 mg or 15 mg weekly produced at least a 15% cut in weight from baseline in 41.4% and 51.8% of participants, respectively, compared with a 2.6% rate of this endpoint in the placebo controls.

So the extent of weight loss seen in in SURMOUNT-2 was somewhat less than was reported in SURMOUNT-1, a finding consistent with many prior studies of incretin-based weight-loss agents, which seem to pack a more potent weight-loss punch in people without type 2 diabetes.

Lilly did not specifically report the treatment effect of tirzepatide on hemoglobin A1c in SURMOUNT-2, only saying that the effect was similar to what had been seen in the series of five SURPASS trials that led to the approval of tirzepatide for type 2 diabetes.

Lilly also reported that the safety profile of tirzepatide in SURMOUNT-2 generally matched what was seen in SURMOUNT-1 as well as in the SURPASS trials. The most common adverse events in SURMOUNT-2 involved gastrointestinal symptoms, such as nausea, diarrhea, and vomiting; these were generally mild to moderate in severity and clustered during the dose-escalation phase at the start of treatment. Treatment discontinuations caused by adverse effects were 3.8% on the 10-mg dosage, 7.4% on the 15-mg dosage, and 3.8% on placebo.

SURMOUNT-2 enrolled patients in the United States, Puerto Rico, and five other countries. All participants also received interventions designed to reduce their calorie intake and increase their physical activity.
 

More SURMOUNT-2 results at ADA in June

Lilly also announced that researchers would report more complete results from SURMOUNT-2 at the 2023 scientific sessions of the American Diabetes Association, being held in San Diego in late June, and publish the findings in a major medical journal.

Results from two additional phase 3 trials of tirzepatide in people with overweight or obesity, SURMOUNT-3 and SURMOUNT-4, are expected later in 2023.

Lilly started an application to the FDA for an indication for weight loss in October 2022 under a fast track designation by the agency, and the data collected in SURMOUNT-2 are expected to complete this application, which would then be subject to an FDA decision within about 6 months. Lilly said in its April 27 press release that it anticipates an FDA decision on this application may occur before the end of 2023.

SURMOUNT-2 and all of the other tirzepatide trials were sponsored by Lilly.

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

The Food and Drug Administration has approved Medtronic Minimed’s 780G automated insulin delivery system with the Guardian 4 sensor.

The latest so-called artificial pancreas system is approved for people aged 7 years and older who have type 1 diabetes. Medtronic will begin taking preorders for the 780G on May 15, 2023. Users of the current MiniMed 770G will be eligible for no-cost remote software upgrades.

Olivier Le Moal/Getty Images

The 780G is currently available in 105 countries. It has been available in Europe since 2020 and in the United Kingdom since 2021. It is the first automated insulin delivery system to automatically administer bolus correction insulin doses every 5 minutes to correct meal-related hyperglycemia.

This so-called meal detection technology doesn’t replace manual premeal boluses but does provide extra insulin if the premeal bolus is skipped or is insufficient.

As with other automated systems, the 780G automatically adjusts basal insulin doses up or down based on glucose levels and trends and shuts off insulin delivery to prevent hypoglycemia. The insulin pump’s infusion set can be worn for 7 days, rather than 3 days as with the older system, and the glucose target level can be set as low as 100 mg/dL.

And in contrast to the older MiniMed 670G system, which tended to frequently boot users out of automated mode, with the 780G, users spent an average of 95% of the time in the automated “SmartGuard” mode.

In the pivotal U.S. trial, overall, patients who used the 780G spent 75% of the time in ideal glucose range (70-180 mg/dL) and 1.8% of the time below that range. Overnight, the figures were 82% and 1.5%, respectively. With the glucose target set at 100 mg/dL and active insulin time set to 2 hours, patients spent 78.8% of time in range without increased hyperglycemia.

In the ADAPT study, with the 780G, there was a 26% increase in time in ideal glucose range and a 1.4% reduction in A1c compared with results for patients who received multiple daily insulin injections with intermittently scanned continuous glucose monitoring, without an increase in hypoglycemia. Overnight, time in range increased 30.2%. The results were sustained at 1 year.

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

The Food and Drug Administration has approved Medtronic Minimed’s 780G automated insulin delivery system with the Guardian 4 sensor.

The latest so-called artificial pancreas system is approved for people aged 7 years and older who have type 1 diabetes. Medtronic will begin taking preorders for the 780G on May 15, 2023. Users of the current MiniMed 770G will be eligible for no-cost remote software upgrades.

Olivier Le Moal/Getty Images

The 780G is currently available in 105 countries. It has been available in Europe since 2020 and in the United Kingdom since 2021. It is the first automated insulin delivery system to automatically administer bolus correction insulin doses every 5 minutes to correct meal-related hyperglycemia.

This so-called meal detection technology doesn’t replace manual premeal boluses but does provide extra insulin if the premeal bolus is skipped or is insufficient.

As with other automated systems, the 780G automatically adjusts basal insulin doses up or down based on glucose levels and trends and shuts off insulin delivery to prevent hypoglycemia. The insulin pump’s infusion set can be worn for 7 days, rather than 3 days as with the older system, and the glucose target level can be set as low as 100 mg/dL.

And in contrast to the older MiniMed 670G system, which tended to frequently boot users out of automated mode, with the 780G, users spent an average of 95% of the time in the automated “SmartGuard” mode.

In the pivotal U.S. trial, overall, patients who used the 780G spent 75% of the time in ideal glucose range (70-180 mg/dL) and 1.8% of the time below that range. Overnight, the figures were 82% and 1.5%, respectively. With the glucose target set at 100 mg/dL and active insulin time set to 2 hours, patients spent 78.8% of time in range without increased hyperglycemia.

In the ADAPT study, with the 780G, there was a 26% increase in time in ideal glucose range and a 1.4% reduction in A1c compared with results for patients who received multiple daily insulin injections with intermittently scanned continuous glucose monitoring, without an increase in hypoglycemia. Overnight, time in range increased 30.2%. The results were sustained at 1 year.

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

The Food and Drug Administration has approved Medtronic Minimed’s 780G automated insulin delivery system with the Guardian 4 sensor.

The latest so-called artificial pancreas system is approved for people aged 7 years and older who have type 1 diabetes. Medtronic will begin taking preorders for the 780G on May 15, 2023. Users of the current MiniMed 770G will be eligible for no-cost remote software upgrades.

Olivier Le Moal/Getty Images

The 780G is currently available in 105 countries. It has been available in Europe since 2020 and in the United Kingdom since 2021. It is the first automated insulin delivery system to automatically administer bolus correction insulin doses every 5 minutes to correct meal-related hyperglycemia.

This so-called meal detection technology doesn’t replace manual premeal boluses but does provide extra insulin if the premeal bolus is skipped or is insufficient.

As with other automated systems, the 780G automatically adjusts basal insulin doses up or down based on glucose levels and trends and shuts off insulin delivery to prevent hypoglycemia. The insulin pump’s infusion set can be worn for 7 days, rather than 3 days as with the older system, and the glucose target level can be set as low as 100 mg/dL.

And in contrast to the older MiniMed 670G system, which tended to frequently boot users out of automated mode, with the 780G, users spent an average of 95% of the time in the automated “SmartGuard” mode.

In the pivotal U.S. trial, overall, patients who used the 780G spent 75% of the time in ideal glucose range (70-180 mg/dL) and 1.8% of the time below that range. Overnight, the figures were 82% and 1.5%, respectively. With the glucose target set at 100 mg/dL and active insulin time set to 2 hours, patients spent 78.8% of time in range without increased hyperglycemia.

In the ADAPT study, with the 780G, there was a 26% increase in time in ideal glucose range and a 1.4% reduction in A1c compared with results for patients who received multiple daily insulin injections with intermittently scanned continuous glucose monitoring, without an increase in hypoglycemia. Overnight, time in range increased 30.2%. The results were sustained at 1 year.

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

Poor diets account for most newly diagnosed type 2 diabetes cases worldwide, a new analysis has found.

More specifically, the modeling study showed that roughly 14 million cases of type 2 diabetes – or 70% of total type 2 diabetes diagnoses in 2018 – were linked with a poor diet, found Meghan O’Hearn, a doctoral student at the Friedman School of Nutrition Science and Policy, Tufts University, Boston, and colleagues. The study was published online in Nature Medicine.

The results also indicate that the greatest burdens of type 2 diabetes were accounted for by excess wheat intake and refined rice (24.6%), excess processed meat consumption (20.3%), and inadequate whole-grain consumption (26.1%). Factors such as drinking too much fruit juice and not eating enough nonstarchy vegetables, nuts, or seeds, had less of an impact on new cases of the disease, the researchers determined.

“These findings can help inform nutritional priorities for clinicians, policymakers, and private sector actors as they encourage healthier dietary choices that address this global epidemic,” Ms. O’Hearn said in a press release.

Prior research has suggested that poor diet contributes to about 40% of type 2 diabetes cases worldwide, the researchers note.

The team attributes their finding of a 70% contribution to the new information in their analysis, such as the first-ever inclusion of refined grains, which was one of the top contributors to diabetes burden, and updated data on dietary habits based on national individual-level dietary surveys rather than agricultural estimates. 

“Our study suggests poor carbohydrate quality is a leading driver of diet-attributable type 2 diabetes globally and with important variation by nation and over time,” said senior author Dariush Mozaffarian, MD, DrPh, MPH, who is the Jean Mayer Professor of Nutrition at the Friedman School of Nutrition Science and Policy.

“These new findings reveal critical areas for national and global focus to improve nutrition and reduce devastating burdens of diabetes,” he noted.

“Left unchecked and with incidence only projected to rise, type 2 diabetes will continue to impact population health, economic productivity, [and] health care system capacity, [as well as] drive health inequities worldwide,” Ms. O’Hearn said.
 

It’s about reducing harmful dietary components

Ms. O’Hearn and colleagues set out to fill information gaps in knowledge about how the global burden of diet-associated type 2 diabetes is impacted by disparities and other factors known to influence risk, including dietary components.

They used information from the Global Dietary Database to study dietary intake in 184 nations from 1990 to 2018. They also studied demographics from multiple sources, estimates of type 2 diabetes incidence around the world, and data on food choices, including the effect of 11 dietary factors, from prior research.

They found that there were 8.6 million more cases of type 2 diabetes in 2018 than in 1990 because of poor diet. 

Regionally, Central and Eastern Europe and Central Asia had the greatest number of type 2 diabetes cases linked to diet, particularly Poland and Russia, where diets tend to be rich in red meat, processed meat, and potatoes. Incidence was also high in Latin America and the Caribbean, especially in Colombia and Mexico, which was attributed to high consumption of sugary drinks and processed meat and low intake of whole grains.

Regions where diet had less of an impact on type 2 diabetes cases included South Asia and sub-Saharan Africa, although the largest increases in type 2 diabetes due to poor diet between 1990 and 2018 were observed in sub-Saharan Africa.

Diet-attributable type 2 diabetes was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, Central and Eastern Europe, and Central Asia, where burdens were larger in rural residents and in lower educated individuals.

Notably, women had lower proportions of diet-related type 2 diabetes, compared with men, and these proportions were inversely related to age.

Excess intake of harmful dietary factors contributed a greater percentage of the burden of type 2 diabetes globally (60.8%) than did insufficient intake of protective dietary factors (39.2%).

“Future research should address whether more complex diet–type 2 diabetes dose–response relationships exist,” the authors conclude.

Ms. O’Hearn has reported receiving research funding from the Gates Foundation, as well as the National Institutes of Health and Vail Innovative Global Research and employment with Food Systems for the Future. Dr. Mozaffarian has reported receiving funding from the National Institutes of Health, the Gates Foundation, the Rockefeller Foundation, Vail Innovative Global Research, and the Kaiser Permanente Fund at East Bay Community Foundation; personal fees from Acasti Pharma, Barilla, Danone, and Motif FoodWorks; is on the scientific advisory board for Beren Therapeutics, Brightseed, Calibrate, DiscernDx, Elysium Health, Filtricine, HumanCo, January, Perfect Day, Tiny Organics and (ended) Day Two and Season Health; has stock ownership in Calibrate and HumanCo; and receives chapter royalties from UpToDate.

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

Poor diets account for most newly diagnosed type 2 diabetes cases worldwide, a new analysis has found.

More specifically, the modeling study showed that roughly 14 million cases of type 2 diabetes – or 70% of total type 2 diabetes diagnoses in 2018 – were linked with a poor diet, found Meghan O’Hearn, a doctoral student at the Friedman School of Nutrition Science and Policy, Tufts University, Boston, and colleagues. The study was published online in Nature Medicine.

The results also indicate that the greatest burdens of type 2 diabetes were accounted for by excess wheat intake and refined rice (24.6%), excess processed meat consumption (20.3%), and inadequate whole-grain consumption (26.1%). Factors such as drinking too much fruit juice and not eating enough nonstarchy vegetables, nuts, or seeds, had less of an impact on new cases of the disease, the researchers determined.

“These findings can help inform nutritional priorities for clinicians, policymakers, and private sector actors as they encourage healthier dietary choices that address this global epidemic,” Ms. O’Hearn said in a press release.

Prior research has suggested that poor diet contributes to about 40% of type 2 diabetes cases worldwide, the researchers note.

The team attributes their finding of a 70% contribution to the new information in their analysis, such as the first-ever inclusion of refined grains, which was one of the top contributors to diabetes burden, and updated data on dietary habits based on national individual-level dietary surveys rather than agricultural estimates. 

“Our study suggests poor carbohydrate quality is a leading driver of diet-attributable type 2 diabetes globally and with important variation by nation and over time,” said senior author Dariush Mozaffarian, MD, DrPh, MPH, who is the Jean Mayer Professor of Nutrition at the Friedman School of Nutrition Science and Policy.

“These new findings reveal critical areas for national and global focus to improve nutrition and reduce devastating burdens of diabetes,” he noted.

“Left unchecked and with incidence only projected to rise, type 2 diabetes will continue to impact population health, economic productivity, [and] health care system capacity, [as well as] drive health inequities worldwide,” Ms. O’Hearn said.
 

It’s about reducing harmful dietary components

Ms. O’Hearn and colleagues set out to fill information gaps in knowledge about how the global burden of diet-associated type 2 diabetes is impacted by disparities and other factors known to influence risk, including dietary components.

They used information from the Global Dietary Database to study dietary intake in 184 nations from 1990 to 2018. They also studied demographics from multiple sources, estimates of type 2 diabetes incidence around the world, and data on food choices, including the effect of 11 dietary factors, from prior research.

They found that there were 8.6 million more cases of type 2 diabetes in 2018 than in 1990 because of poor diet. 

Regionally, Central and Eastern Europe and Central Asia had the greatest number of type 2 diabetes cases linked to diet, particularly Poland and Russia, where diets tend to be rich in red meat, processed meat, and potatoes. Incidence was also high in Latin America and the Caribbean, especially in Colombia and Mexico, which was attributed to high consumption of sugary drinks and processed meat and low intake of whole grains.

Regions where diet had less of an impact on type 2 diabetes cases included South Asia and sub-Saharan Africa, although the largest increases in type 2 diabetes due to poor diet between 1990 and 2018 were observed in sub-Saharan Africa.

Diet-attributable type 2 diabetes was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, Central and Eastern Europe, and Central Asia, where burdens were larger in rural residents and in lower educated individuals.

Notably, women had lower proportions of diet-related type 2 diabetes, compared with men, and these proportions were inversely related to age.

Excess intake of harmful dietary factors contributed a greater percentage of the burden of type 2 diabetes globally (60.8%) than did insufficient intake of protective dietary factors (39.2%).

“Future research should address whether more complex diet–type 2 diabetes dose–response relationships exist,” the authors conclude.

Ms. O’Hearn has reported receiving research funding from the Gates Foundation, as well as the National Institutes of Health and Vail Innovative Global Research and employment with Food Systems for the Future. Dr. Mozaffarian has reported receiving funding from the National Institutes of Health, the Gates Foundation, the Rockefeller Foundation, Vail Innovative Global Research, and the Kaiser Permanente Fund at East Bay Community Foundation; personal fees from Acasti Pharma, Barilla, Danone, and Motif FoodWorks; is on the scientific advisory board for Beren Therapeutics, Brightseed, Calibrate, DiscernDx, Elysium Health, Filtricine, HumanCo, January, Perfect Day, Tiny Organics and (ended) Day Two and Season Health; has stock ownership in Calibrate and HumanCo; and receives chapter royalties from UpToDate.

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

Poor diets account for most newly diagnosed type 2 diabetes cases worldwide, a new analysis has found.

More specifically, the modeling study showed that roughly 14 million cases of type 2 diabetes – or 70% of total type 2 diabetes diagnoses in 2018 – were linked with a poor diet, found Meghan O’Hearn, a doctoral student at the Friedman School of Nutrition Science and Policy, Tufts University, Boston, and colleagues. The study was published online in Nature Medicine.

The results also indicate that the greatest burdens of type 2 diabetes were accounted for by excess wheat intake and refined rice (24.6%), excess processed meat consumption (20.3%), and inadequate whole-grain consumption (26.1%). Factors such as drinking too much fruit juice and not eating enough nonstarchy vegetables, nuts, or seeds, had less of an impact on new cases of the disease, the researchers determined.

“These findings can help inform nutritional priorities for clinicians, policymakers, and private sector actors as they encourage healthier dietary choices that address this global epidemic,” Ms. O’Hearn said in a press release.

Prior research has suggested that poor diet contributes to about 40% of type 2 diabetes cases worldwide, the researchers note.

The team attributes their finding of a 70% contribution to the new information in their analysis, such as the first-ever inclusion of refined grains, which was one of the top contributors to diabetes burden, and updated data on dietary habits based on national individual-level dietary surveys rather than agricultural estimates. 

“Our study suggests poor carbohydrate quality is a leading driver of diet-attributable type 2 diabetes globally and with important variation by nation and over time,” said senior author Dariush Mozaffarian, MD, DrPh, MPH, who is the Jean Mayer Professor of Nutrition at the Friedman School of Nutrition Science and Policy.

“These new findings reveal critical areas for national and global focus to improve nutrition and reduce devastating burdens of diabetes,” he noted.

“Left unchecked and with incidence only projected to rise, type 2 diabetes will continue to impact population health, economic productivity, [and] health care system capacity, [as well as] drive health inequities worldwide,” Ms. O’Hearn said.
 

It’s about reducing harmful dietary components

Ms. O’Hearn and colleagues set out to fill information gaps in knowledge about how the global burden of diet-associated type 2 diabetes is impacted by disparities and other factors known to influence risk, including dietary components.

They used information from the Global Dietary Database to study dietary intake in 184 nations from 1990 to 2018. They also studied demographics from multiple sources, estimates of type 2 diabetes incidence around the world, and data on food choices, including the effect of 11 dietary factors, from prior research.

They found that there were 8.6 million more cases of type 2 diabetes in 2018 than in 1990 because of poor diet. 

Regionally, Central and Eastern Europe and Central Asia had the greatest number of type 2 diabetes cases linked to diet, particularly Poland and Russia, where diets tend to be rich in red meat, processed meat, and potatoes. Incidence was also high in Latin America and the Caribbean, especially in Colombia and Mexico, which was attributed to high consumption of sugary drinks and processed meat and low intake of whole grains.

Regions where diet had less of an impact on type 2 diabetes cases included South Asia and sub-Saharan Africa, although the largest increases in type 2 diabetes due to poor diet between 1990 and 2018 were observed in sub-Saharan Africa.

Diet-attributable type 2 diabetes was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, Central and Eastern Europe, and Central Asia, where burdens were larger in rural residents and in lower educated individuals.

Notably, women had lower proportions of diet-related type 2 diabetes, compared with men, and these proportions were inversely related to age.

Excess intake of harmful dietary factors contributed a greater percentage of the burden of type 2 diabetes globally (60.8%) than did insufficient intake of protective dietary factors (39.2%).

“Future research should address whether more complex diet–type 2 diabetes dose–response relationships exist,” the authors conclude.

Ms. O’Hearn has reported receiving research funding from the Gates Foundation, as well as the National Institutes of Health and Vail Innovative Global Research and employment with Food Systems for the Future. Dr. Mozaffarian has reported receiving funding from the National Institutes of Health, the Gates Foundation, the Rockefeller Foundation, Vail Innovative Global Research, and the Kaiser Permanente Fund at East Bay Community Foundation; personal fees from Acasti Pharma, Barilla, Danone, and Motif FoodWorks; is on the scientific advisory board for Beren Therapeutics, Brightseed, Calibrate, DiscernDx, Elysium Health, Filtricine, HumanCo, January, Perfect Day, Tiny Organics and (ended) Day Two and Season Health; has stock ownership in Calibrate and HumanCo; and receives chapter royalties from UpToDate.

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

Drinking sugar-sweetened beverages (SSBs) increases the risk of cardiovascular disease and all-cause death in people with type 2 diabetes, reveals a U.S. study that also suggests switching to coffee, tea, or low-fat milk may diminish these risks.

The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.

The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.

“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.

“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.


 

Choice of drink matters

Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.

Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.

There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.

Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”

“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.

Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
 

Expanding the evidence

It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.

Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.

To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.

For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.

Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.

During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.

Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).

In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.

The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.

Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.

The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”

The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.

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

Drinking sugar-sweetened beverages (SSBs) increases the risk of cardiovascular disease and all-cause death in people with type 2 diabetes, reveals a U.S. study that also suggests switching to coffee, tea, or low-fat milk may diminish these risks.

The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.

The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.

“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.

“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.


 

Choice of drink matters

Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.

Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.

There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.

Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”

“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.

Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
 

Expanding the evidence

It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.

Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.

To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.

For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.

Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.

During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.

Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).

In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.

The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.

Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.

The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”

The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.

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

Drinking sugar-sweetened beverages (SSBs) increases the risk of cardiovascular disease and all-cause death in people with type 2 diabetes, reveals a U.S. study that also suggests switching to coffee, tea, or low-fat milk may diminish these risks.

The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.

The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.

“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.

“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.


 

Choice of drink matters

Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.

Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.

There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.

Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”

“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.

Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
 

Expanding the evidence

It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.

Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.

To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.

For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.

Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.

During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.

Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).

In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.

The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.

Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.

The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”

The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.

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

I believe that the diagnosis of type 2 diabetes mellitus (T2DM) should be broadened to match the glycemic thresholds currently used for prediabetes. This would eliminate the need for a separate category, the “prediabetes” nomenclature, and allow for earlier therapeutic intervention in patients. Current diabetes diagnostic thresholds do not reflect the latest advancements in T2DM understanding. The latest in T2DM research suggests that intervening and treating prediabetes earlier could potentially offer better clinical outcomes and enhance patients’ quality of life, as cell and tissue damage occurs early and leads to dysfunction prior to a diabetes diagnosis.¹ T2DM is a highly complex disease with multifactorial causes beyond hyperglycemia that should be considered, such as hyperlipidemia, insulin resistance, hyperinsulinemia, and autoimmune inflammatory mechanisms that lead to β-cell dysfunction or failure, which results in hyperglycemia. 

Prediabetes is associated with micro- and macrovascular complications that can occur early in the progression to frank disease state.^1,2 This phase of diabetes also includes insulin resistance, impaired incretin action, insulin hypersecretion, increased lipolysis, and ectopic lipid storage—all of which damage β cells. These dysfunctions are also present in the frank diabetic disease state.^3,4 Furthermore, diabetic retinopathy occurs in 8% to 12% of patients with prediabetes, and retinopathy begins earlier than previously thought, with neuroinflammation occurring even before vascular damage.^5,6 Unfortunately, these neuro-inflammatory lesions cannot be detected with the typical instruments used in an ophthalmologist’s office. 

It is believed that, through the principle of metabolic memory, even a moderate increase or episodic spikes in blood glucose can lead to negative effects in prediabetic patients who are susceptible to T2DM.^1,5 Therefore, a lower diabetes diagnostic threshold could allow for earlier, more precise, and personalized therapies based on each patient’s individual risk factors and biomarkers. With a diagnosis of T2DM at the current prediabetes threshold, patients could receive treatment  covered by health insurance while in the “prediabetic” state—treatment that would not have been previously approved. Patients should be treated earlier and on an individual basis with counseling on diet and lifestyle changes and antidiabetic agents to reduce glycemic levels, preserve β cells, and reduce cardiovascular [CV] or renal risk, among other complications.^6,7 

 Moreover, the newer agents for treating diabetes such as glucagon-like pepetide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, which are also associated with reduction in adverse CV and/or renal outcomes, could be beneficial if administered early in the prediabetic stage of disease.^8,9 

Early lifestyle and pharmacologic interventions can reduce the rate of progression from prediabetes to diabetes as well as complications and associated conditions, and even potentially result in remission or a full reversal of diabetes. These “side benefits” of lowering the diabetes diagnostic threshold (over and above glycemic control) make any cost-effectiveness calculations all the more advantageous to individual patients as well as to society.

Given the numerous benefits of earlier intervention for diabetes treatment, I believe a call to re-evaluate the current diabetes diagnostic threshold is in order, as it will do a great service for all patients who are currently at risk for developing T2DM.

I believe that the diagnosis of type 2 diabetes mellitus (T2DM) should be broadened to match the glycemic thresholds currently used for prediabetes. This would eliminate the need for a separate category, the “prediabetes” nomenclature, and allow for earlier therapeutic intervention in patients. Current diabetes diagnostic thresholds do not reflect the latest advancements in T2DM understanding. The latest in T2DM research suggests that intervening and treating prediabetes earlier could potentially offer better clinical outcomes and enhance patients’ quality of life, as cell and tissue damage occurs early and leads to dysfunction prior to a diabetes diagnosis.¹ T2DM is a highly complex disease with multifactorial causes beyond hyperglycemia that should be considered, such as hyperlipidemia, insulin resistance, hyperinsulinemia, and autoimmune inflammatory mechanisms that lead to β-cell dysfunction or failure, which results in hyperglycemia. 

Prediabetes is associated with micro- and macrovascular complications that can occur early in the progression to frank disease state.^1,2 This phase of diabetes also includes insulin resistance, impaired incretin action, insulin hypersecretion, increased lipolysis, and ectopic lipid storage—all of which damage β cells. These dysfunctions are also present in the frank diabetic disease state.^3,4 Furthermore, diabetic retinopathy occurs in 8% to 12% of patients with prediabetes, and retinopathy begins earlier than previously thought, with neuroinflammation occurring even before vascular damage.^5,6 Unfortunately, these neuro-inflammatory lesions cannot be detected with the typical instruments used in an ophthalmologist’s office. 

It is believed that, through the principle of metabolic memory, even a moderate increase or episodic spikes in blood glucose can lead to negative effects in prediabetic patients who are susceptible to T2DM.^1,5 Therefore, a lower diabetes diagnostic threshold could allow for earlier, more precise, and personalized therapies based on each patient’s individual risk factors and biomarkers. With a diagnosis of T2DM at the current prediabetes threshold, patients could receive treatment  covered by health insurance while in the “prediabetic” state—treatment that would not have been previously approved. Patients should be treated earlier and on an individual basis with counseling on diet and lifestyle changes and antidiabetic agents to reduce glycemic levels, preserve β cells, and reduce cardiovascular [CV] or renal risk, among other complications.^6,7 

 Moreover, the newer agents for treating diabetes such as glucagon-like pepetide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, which are also associated with reduction in adverse CV and/or renal outcomes, could be beneficial if administered early in the prediabetic stage of disease.^8,9 

Early lifestyle and pharmacologic interventions can reduce the rate of progression from prediabetes to diabetes as well as complications and associated conditions, and even potentially result in remission or a full reversal of diabetes. These “side benefits” of lowering the diabetes diagnostic threshold (over and above glycemic control) make any cost-effectiveness calculations all the more advantageous to individual patients as well as to society.

Given the numerous benefits of earlier intervention for diabetes treatment, I believe a call to re-evaluate the current diabetes diagnostic threshold is in order, as it will do a great service for all patients who are currently at risk for developing T2DM.

I believe that the diagnosis of type 2 diabetes mellitus (T2DM) should be broadened to match the glycemic thresholds currently used for prediabetes. This would eliminate the need for a separate category, the “prediabetes” nomenclature, and allow for earlier therapeutic intervention in patients. Current diabetes diagnostic thresholds do not reflect the latest advancements in T2DM understanding. The latest in T2DM research suggests that intervening and treating prediabetes earlier could potentially offer better clinical outcomes and enhance patients’ quality of life, as cell and tissue damage occurs early and leads to dysfunction prior to a diabetes diagnosis.¹ T2DM is a highly complex disease with multifactorial causes beyond hyperglycemia that should be considered, such as hyperlipidemia, insulin resistance, hyperinsulinemia, and autoimmune inflammatory mechanisms that lead to β-cell dysfunction or failure, which results in hyperglycemia. 

Prediabetes is associated with micro- and macrovascular complications that can occur early in the progression to frank disease state.^1,2 This phase of diabetes also includes insulin resistance, impaired incretin action, insulin hypersecretion, increased lipolysis, and ectopic lipid storage—all of which damage β cells. These dysfunctions are also present in the frank diabetic disease state.^3,4 Furthermore, diabetic retinopathy occurs in 8% to 12% of patients with prediabetes, and retinopathy begins earlier than previously thought, with neuroinflammation occurring even before vascular damage.^5,6 Unfortunately, these neuro-inflammatory lesions cannot be detected with the typical instruments used in an ophthalmologist’s office. 

It is believed that, through the principle of metabolic memory, even a moderate increase or episodic spikes in blood glucose can lead to negative effects in prediabetic patients who are susceptible to T2DM.^1,5 Therefore, a lower diabetes diagnostic threshold could allow for earlier, more precise, and personalized therapies based on each patient’s individual risk factors and biomarkers. With a diagnosis of T2DM at the current prediabetes threshold, patients could receive treatment  covered by health insurance while in the “prediabetic” state—treatment that would not have been previously approved. Patients should be treated earlier and on an individual basis with counseling on diet and lifestyle changes and antidiabetic agents to reduce glycemic levels, preserve β cells, and reduce cardiovascular [CV] or renal risk, among other complications.^6,7 

 Moreover, the newer agents for treating diabetes such as glucagon-like pepetide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, which are also associated with reduction in adverse CV and/or renal outcomes, could be beneficial if administered early in the prediabetic stage of disease.^8,9 

Early lifestyle and pharmacologic interventions can reduce the rate of progression from prediabetes to diabetes as well as complications and associated conditions, and even potentially result in remission or a full reversal of diabetes. These “side benefits” of lowering the diabetes diagnostic threshold (over and above glycemic control) make any cost-effectiveness calculations all the more advantageous to individual patients as well as to society.

Given the numerous benefits of earlier intervention for diabetes treatment, I believe a call to re-evaluate the current diabetes diagnostic threshold is in order, as it will do a great service for all patients who are currently at risk for developing T2DM.

Medicare is now covering continuous glucose monitoring (CGM) for all beneficiaries with diabetes who use insulin, as well as those with a “history of problematic hypoglycemia.”

The new policy decision, announced earlier this year by the Centers for Medicare and Medicaid Services, means that coverage is expanded to those who take even just a single dose of basal insulin daily or who don’t take insulin but who for other reasons experience “problematic” hypoglycemia, defined as a history of more than one level 2 event (glucose < 54 mg/dL) or at least one level 3 event (< 54 mg/dL requiring assistance).

Previously, coverage was limited to those taking frequent daily insulin doses.  

The additional number of people covered, most with type 2 diabetes, is estimated to be at least 1.5 million. That number could more than double if private insurers follow suit, reported an industry analyst.

Chuck Henderson, chief executive officer of the American Diabetes Association, said in a statement: “We applaud CMS’ decision allowing for all insulin-dependent people as well as others who have a history of problematic hypoglycemia to have access to a continuous glucose monitor, a potentially life-saving tool for diabetes management.”

According to Dexcom, which manufacturers the G6 and the recently approved G7 CGMs, the decision was based in part on their MOBILE study. The trial demonstrated the benefit of CGM in people with type 2 diabetes who use only basal insulin or have a history of problematic hypoglycemic events.

On April 14, Abbott, which manufactures the Freestyle Libre 2 and the recently approved Libre 3, received clearance from the U.S. Food and Drug Administration for the Libre 3’s stand-alone reader device. Previously, the Libre 3 had been approved for use only with a smartphone app. The small handheld reader is considered durable medical equipment, making it eligible for Medicare coverage. Abbott is “working on having the FreeStyle Libre 3 system available to Medicare beneficiaries,” the company said in a statement.

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

Medicare is now covering continuous glucose monitoring (CGM) for all beneficiaries with diabetes who use insulin, as well as those with a “history of problematic hypoglycemia.”

The new policy decision, announced earlier this year by the Centers for Medicare and Medicaid Services, means that coverage is expanded to those who take even just a single dose of basal insulin daily or who don’t take insulin but who for other reasons experience “problematic” hypoglycemia, defined as a history of more than one level 2 event (glucose < 54 mg/dL) or at least one level 3 event (< 54 mg/dL requiring assistance).

Previously, coverage was limited to those taking frequent daily insulin doses.  

The additional number of people covered, most with type 2 diabetes, is estimated to be at least 1.5 million. That number could more than double if private insurers follow suit, reported an industry analyst.

Chuck Henderson, chief executive officer of the American Diabetes Association, said in a statement: “We applaud CMS’ decision allowing for all insulin-dependent people as well as others who have a history of problematic hypoglycemia to have access to a continuous glucose monitor, a potentially life-saving tool for diabetes management.”

According to Dexcom, which manufacturers the G6 and the recently approved G7 CGMs, the decision was based in part on their MOBILE study. The trial demonstrated the benefit of CGM in people with type 2 diabetes who use only basal insulin or have a history of problematic hypoglycemic events.

On April 14, Abbott, which manufactures the Freestyle Libre 2 and the recently approved Libre 3, received clearance from the U.S. Food and Drug Administration for the Libre 3’s stand-alone reader device. Previously, the Libre 3 had been approved for use only with a smartphone app. The small handheld reader is considered durable medical equipment, making it eligible for Medicare coverage. Abbott is “working on having the FreeStyle Libre 3 system available to Medicare beneficiaries,” the company said in a statement.

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

Medicare is now covering continuous glucose monitoring (CGM) for all beneficiaries with diabetes who use insulin, as well as those with a “history of problematic hypoglycemia.”

The new policy decision, announced earlier this year by the Centers for Medicare and Medicaid Services, means that coverage is expanded to those who take even just a single dose of basal insulin daily or who don’t take insulin but who for other reasons experience “problematic” hypoglycemia, defined as a history of more than one level 2 event (glucose < 54 mg/dL) or at least one level 3 event (< 54 mg/dL requiring assistance).

Previously, coverage was limited to those taking frequent daily insulin doses.  

The additional number of people covered, most with type 2 diabetes, is estimated to be at least 1.5 million. That number could more than double if private insurers follow suit, reported an industry analyst.

Chuck Henderson, chief executive officer of the American Diabetes Association, said in a statement: “We applaud CMS’ decision allowing for all insulin-dependent people as well as others who have a history of problematic hypoglycemia to have access to a continuous glucose monitor, a potentially life-saving tool for diabetes management.”

According to Dexcom, which manufacturers the G6 and the recently approved G7 CGMs, the decision was based in part on their MOBILE study. The trial demonstrated the benefit of CGM in people with type 2 diabetes who use only basal insulin or have a history of problematic hypoglycemic events.

On April 14, Abbott, which manufactures the Freestyle Libre 2 and the recently approved Libre 3, received clearance from the U.S. Food and Drug Administration for the Libre 3’s stand-alone reader device. Previously, the Libre 3 had been approved for use only with a smartphone app. The small handheld reader is considered durable medical equipment, making it eligible for Medicare coverage. Abbott is “working on having the FreeStyle Libre 3 system available to Medicare beneficiaries,” the company said in a statement.

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

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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