Randomized in phase 2 clinical study In adults with type 2 diabetes and obesity, published in JAMA Network Open, the investigational drug induced bimagrumab (BYM338, Novartis) – a monoclonal antibody that blocks activin type II receptors and stimulates skeletal muscle growth a large reduction in total body fat mass and A1c and significant increase in lean mass compared to placebo.
Adults with type 2 diabetes and overweight or obese who were given a once-monthly monoclonal antibody infusion showed significant reductions in fat mass and muscle gains compared to placebo, according to results from a phase 2 study.
“What suggests is that there may be an entirely new mechanism at play here.” Because patients who received bimagrumab didn’t eat less, they lost the same amount of weight reported for weight loss drugs that decrease appetite, Lee says. M. Kaplan, MD, Ph.D. found that the 6.5% weight loss in the bimagrumab group was similar to that of anti-obesity drugs that suppress appetite.
The efficacy and safety results “Suggest that blocking the activin receptor with bimagrumab may offer a novel pharmacological approach to the treatment of patients with type 2 diabetes who are overly obese” Steven B. Heymsfield, MD, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge
Bimagrumab, a human monoclonal antibody that blocks activin type II receptors and stimulates muscle growth, was not initially studied as a treatment for obesity. Dr. Steven B. Heymsfield, FTOS, a professor in the Department of Metabolism and Body Composition at Pennington Biomedical Research Center, Louisiana State University, said Healio. The drug was originally touted as a potential breakthrough therapy for people with sporadic inclusion body myositis, a rare muscle wasting disease. However, the drug failed to meet its primary endpoint in a Phase 2b / 3 study, Novartis announced in a 2016 press release.
“When the researchers did the preclinical work, there was absolutely no signal on the adipose tissue. It was all muscle growth. ” Heymsfield said in an interview. “You had no reason to suspect it because [activin type II receptors] are mainly muscles. In initial human studies, they saw a signal for adipose tissue and ran a proof-of-concept study to see if the effects of adipose tissue were significant. That was the reason for the current investigation – a phase 2 study with body fat as the primary endpoint. To date there is no clear mechanism. “
Study design
Heymsfield and colleagues analyzed data from 75 adults with type 2 diabetes with overweight or obesity, defined as a BMI between 28 kg / m² and 40 kg / m² (mean age 60 years; mean BMI 32.9 kg / m²; mean body weight 93, 6) kg; mean fat mass 35.4 kg; mean HbA1c 7.8%). The study was carried out from February 2017 to May 2019. Researchers randomly assigned participants an IV infusion of bimagrumab (10 mg / kg up to 1,200 mg in 5% dextrose solution; n = 37; 62.2% women) or placebo (5% dextrose solution); n = 38; 77.3% women) every 4 weeks for 48 weeks. Both groups received diet and exercise advice. The primary endpoint was the smallest square mean change in total body fat mass from baseline to week 48 as measured by DXA; secondary and exploratory endpoints were lean mass, waist circumference, HbA1c, and changes in body weight from baseline to week 48.
Fat mass versus body weight
At week 48, participants in the bimagrumab group had a mean fat mass loss of –20.5% (mean –7.5 kg; 80% CI –8.3 to –6.6) versus a mean of –0.5% the participants in the placebo group (-0.18 kg; 80% CI, -0.99 to -0.63).
The participants who received bimagrumab also had a mean increase in lean mass of 3.6% (mean 1.7 kg; 80% CI 1.1-2.3) compared to a mean decrease in lean mass of -0, 8% for the placebo group (mean –0.4 kg; 80% CI, –1 to 0.1).
Waist circumference decreased an average of 9 cm in the bimagrumab group versus an increase of 0.5 cm in the placebo group (P <0.001), and HbA1c decreased 0.76 percentage points compared to 0.04 percentage points in the bimagrumab group in the placebo group (P = 0.005). Weight loss was also greater in the bimagrumab group versus placebo (mean -5.9 kg versus -0.8 kg; P <0.001).
The safety and tolerability profile of bimagrumab was consistent with previous studies. Mild diarrhea and muscle cramps were the most commonly reported adverse events in the bimagrumab group; One patient in the bimagrumab group developed pancreatitis.
“What surprised me the most was the extent of the effects on body fat.” Heymsfield said. “The effect is real; This is not an isolated incident. People lost 7.5 pounds of fat, or nearly 16 to 20 pounds of fat. This is a significant fat loss, especially for people with diabetes who are not responding very well to obesity treatment. “
Bimagrumab and the possible mechanism behind the new knowledge are exciting. However, the next steps in the drug’s pipeline are unclear, Heymsfield said. Novartis decided to license the drug and did not disclose who the licensee is, he added.
“It’s not deadHeymsfield said about therapy. “To be honest, the diabetes section is nice overfilled. You can take metformin for a dime a day. Monoclonal antibodies are also expensive. “
The researchers also noted a signal of elevated pancreatic enzymes, the origin or meaning of which is unclear, he said.
“The real future of this drug is figuring out the mechanism, working it through, and finding targets that are drugged.” Heymsfield said. “This study shows the beguiling nature of weight changes. These people lost more fat than body weight. One cannot always rely on weight as an index of effectiveness. “
