In a phase 2 randomized clinical trial of adults with type 2 diabetes and obesity, investigational drug bimagrumab (BYM338, Novartis) – a monoclonal antibody that blocks activin type II receptors and stimulates skeletal muscle growth – led to big reductions in total body fat mass and A1c and significant increases in lean mass compared with placebo.
The efficacy and safety findings “suggest that blockade of the activin receptor with bimagrumab could provide a novel pharmacologic approach for managing patients with type 2 diabetes with excess adiposity,” Steven B. Heymsfield, MD, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and colleagues reported in their study, published online Jan. 13 in JAMA Network Open.
Preliminary findings from the study of 75 patients treated for 48 weeks – in which neither group ate less despite intensive nutrition advice – were presented at Obesity Week in 2019.
As reported then, Lee M. Kaplan, MD, PhD, noted that the 6.5% weight loss in the bimagrumab group was similar to that seen with antiobesity medications that suppress appetite.
“What it suggests,” he said in an interview, “is that there may be a completely new mechanism at play here,” because patients receiving bimagrumab weren’t eating less but were losing the same amount of weight as reported for weight-loss drugs that work by decreasing appetite.
“Is this going to be the kind of complementary drug with a different mechanism that’s going to augment the effects of other drugs?” wondered Dr. Kaplan, director of the Obesity, Metabolism & Nutrition Institute at Massachusetts General Hospital, Boston, who has previously served as a scientific consultant to Novartis.
Asked about future plans for bimagrumab, a Novartis spokesperson said in an interview, “We are currently reviewing the program strategy and considering next steps.”
Four FDA-approved weight-loss drugs now approved
The Food and Drug Administration approval for lorcaserin (Belviq, Belviq XR, Eisai) for weight loss was rescinded on Feb. 13, 2020, when a postmarketing trial revealed an increased occurrence of cancer, leaving four drugs approved for weight loss in the United States, plus several drugs in development, Dr. Heymsfield and colleagues wrote.
The current phase 2 trial was designed to determine the safety and efficacy of bimagrumab – which had originally been studied to see if it would increase lean muscle mass in people with sarcopenia – on total body fat mass and glycemic control in patients with type 2 diabetes and overweight or obesity.
Researchers enrolled 75 adults at eight sites in the United States and one in Wales, United Kingdom, from 2017 to 2019.
On average, patients were 60 years old with an A1c of 7.8% and a body mass index of 32.9 kg/m2; they weighed 93.6 kg and had a fat mass of 35 kg.
Patients received an intravenous infusion of bimagrumab (10 mg/kg up to 1,200 mg in 5% dextrose solution) or placebo (5% dextrose solution) every 4 weeks for 48 weeks. They met with a registered dietitian at each monthly study visit and had a virtual check-in between visits.
Participants were advised to follow a diet that would cut 500 calories a day and encouraged to follow the American Diabetes Association walking program.
Body fat mass was measured by dual-energy x-ray absorptiometry (DEXA).
There were more women in the bimagrumab group than in the placebo group (62% vs. 32%), but baseline BMI, total body fat mass, and A1c were similar in both groups.