Can combination therapy beat monotherapy for weight loss? The phase 2 BELIEVE trial of bimagrumab plus semaglutide versus bimagrumab monotherapy may have the answer.

“Semaglutide mainly acts through appetite suppression through the central nervous system and peripheral mechanisms,” said Steven B. Heymsfield, MD, Professor of Medicine at the Pennington Biomedical Research Center. “Bimagrumab was developed for sarcopenia—muscle wasting with age. It binds to activin receptors to stimulate muscle growth. Activin receptors are also present on fat cells.”

Dr. Heymsfield will present the efficacy and safety results of BELIEVE during Can We Improve the Quality of Weight Loss by Augmenting Fat Mass Loss While Preserving Lean Mass? The BELIEVE Study of Bimagrumab + Semaglutide on Monday, June 23, from 8:00–9:30 a.m., in Room W375 A of the McCormick Place Convention Center. On-demand access to recorded presentations will be available to registered participants following the conclusion of the 85^th Scientific Sessions, from June 25–August 25.

BELIEVE builds on earlier data showing a 20.5% decline in fat mass, a 3.6% increase in lean mass, a 9 cm decline in waist circumference, and 6.5% decline in body weight for bimagrumab versus placebo.

Ronenn Roubenoff, MD, MHS, Roubenoff Consulting, LLC, will explore activin pathway inhibition in adipose tissue and  muscle with bimagrumab.

“One of the concerns about the use of glucagon-like peptide-1 (GLP-1) and other incretin hormones is concern about the loss of lean mass,” said Louis J. Aronne, MD, FACP, DABOM, Sanford I. Weill Professor of Metabolic Research at the Weil Cornell Medicine Comprehensive Weight Control Center. He will share BELIEVE results related to visceral fat, inflammation, and metabolic endpoints.

“There is more fat loss than lean loss, that’s very clear,” Dr. Aronne continued. “But in some cases, the lean mass is as much as 40% of the total weight that is lost.”

The trial randomized about 500 individuals at 26 centers across the United States, Australia, and New Zealand to semaglutide plus bimagrumab versus semaglutide plus placebo for 72 weeks. Participants had a baseline body mass index (BMI)  ≥30 or  ≥27 with one or more obesity-associated comorbidities including hypertension, insulin resistance, sleep apnea, or dyslipidemia. All participants had failed at least one behavioral attempt to lose body weight.

The primary outcome is change in body weight. Secondary outcomes include change in waist circumference, change in BMI, change in percent body fat, change in visceral and subcutaneous adipose tissue, change in trunk fat mass, percentage of weight loss due to fat mass or lean mass, quality of life, and more.

“If you go back 20, 30 years, everyone said weight loss is what we have to focus on,” Dr. Heymsfield said. “Now that it’s clear you can get very large weight loss, it is the quality of weight loss that is becoming more important.”

Penelope Montgomery, MD, Medical Director, Optimal Clinical Trials, New Zealand, will discuss the BELIEVE study design. Ania M. Jastreboff, MD, PhD, Associate Professor of Endocrinology at Yale School of Medicine, Director of the Yale Obesity Research Center, Co-Director of the Yale Center for Weight Management, and Medical Director of the Yale Stress Center, will join a panel discussion on the trial.