NEW YORK (Reuters Health) – In overweight and obese adults at high cardiovascular risk, once-daily subcutaneous liraglutide plus changes in diet and physical activity reduced visceral fat, a single-center phase 4 placebo-controlled trial showed.

“We have good evidence that visceral fat is associated with a higher risk for diabetes and heart disease than subcutaneous fat,” Dr. Parag Joshi of the UT Southwestern Medical Center in Dallas told Reuters Health by email. “We knew liraglutide helps with weight loss; however, we didn’t know how it affects these different types of fat.”

“It is reassuring to know that the type of weight that is lost (with liraglutide) is associated with higher risk, and this is an effective way to lose that type of fat,” he said. “It would be great to show that the more visceral fat lost led to better outcomes (fewer heart attacks or new diagnoses of diabetes) but that would take a very large study.”

As reported in The Lancet Diabetes and Endocrinology, Dr. Joshi and colleagues randomized 185 adults with a BMI of at least 30 kg/m2 or BMI of at least 27 kg/m2 with metabolic syndrome but without diabetes to 40 weeks of once-daily subcutaneous liraglutide 3.0 mg or placebo, in addition to a 500 kcal-deficient diet and guideline-recommended physical activity counseling.

One hundred and twenty-eight participants were included in the final analysis: mean age, 50; 92% women; 37%, Black; 24%, Hispanic; and mean BMI, 37.7 kg/m2.

The primary endpoint was percentage reduction in visceral fat measured with MRI.

The mean change in visceral fat over a median 36.2 weeks was −12.49% with liraglutide versus −1.63% with placebo.

The authors note, “The relative effects of liraglutide on fat reduction were two times greater in the abdominal viscera and six times greater in the liver than seen on overall bodyweight.”

The effects seemed consistent across subgroups of age, sex, race/ethnicity, BMI, and baseline prediabetes.

The most frequently reported adverse events were gastrointestinal-related (47% with liraglutide and 13% with placebo) and upper respiratory tract infections (11% versus 15%).

The authors conclude, “Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes.”

Dr. Vincent Fong of the UC College of Medicine in Cincinnati, a specialist in internal medicine and endocrinology-diabetes and metabolism, commented on the study in an email to Reuters Health. “We have known for some time that visceral and ectopic fat were much more associated with metabolic dysfunction when compared to subcutaneous fat, and that liraglutide has shown ability to reduce both in previous studies in patients with diabetes. There are some data that other medications of the same class (GLP1 receptor agonists) also have similar effects.”

“What is good about this study is that it was a prospective randomized controlled trial with a relatively large sample size and detailed measurements of different fat depots,” he said. “What is new is that none of the participants had diabetes, and most did not even have prediabetes.”

“So, as a physician, if that was a distinction that you used to decide whether or not to prescribe liraglutide, then this study would make a very big difference in your practice,” he said. “If not, then it is still helpful in that it is provided high quality data supporting its benefits reducing metabolically active fat, but maybe does not drastically change prescribing practices.”

However, he noted that “in reality, liraglutide is very cost-prohibitive and that is a much larger factor in prescribing decisions.” Very few payors cover the 3 mg dose, which is indicated for obesity, and was the dosage used in the study, he said. “It would be very difficult for most people to afford the treatment, so if cost doesn’t change, then it doesn’t matter what the benefit is if patients can’t afford it.”

“Similar studies using medications of the same class are needed to prove whether this is a class effect, as many believe, versus a liraglutide-specific benefit,” he added.

“It is my opinion that it is likely a class effect, so in agreement with ADA Standards of Care for treatment of diabetes, GLP1 receptor agonist medications should be considered early in patients with established cardiovascular disease or high risk of cardiovascular disease,” Dr. Fong concluded.

The study was funded by NovoNordisk. Dr. Joshi and one coauthor have received fees from the company.

SOURCE: https://bit.ly/3mGbQ4b and https://bit.ly/2WAOceO Lancet Diabetes and Endocrinology, online August 3, 2021.

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