Bimagrumab, an antibody that blocks activin type II receptors and stimulates skeletal muscle growth, is safe and effective for treating excess adiposity and metabolic disturbances of adult patients with obesity and type 2 diabetes, according to the findings reported in the paper, 'Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity - A Phase 2 Randomized Clinical Trial', published in JAMA Network.
"These exciting results suggest that there may be a novel mechanism for achieving weight loss with a profound loss of body fat and an increase in lean mass, along with other metabolic benefits," said Dr Steve Heymsfield, past president of The Obesity Society corresponding author of the study and professor and director of the Metabolism and Body Composition Laboratory at the Pennington Biomedical Research Center in Baton Rouge, LA.
A total of 75 patients with type 2 diabetes with a BMI 28-40 and glycated haemoglobin A1c levels between 6.5 percent and 10 percent were selected for the phase 2 randomised clinical trial. Patients were injected with either Bimagrumab or a placebo (a dextrose solution) every four weeks for 48 weeks. Both groups received diet and exercise counselling. The research took place at nine sites in the UK and the US from February 2017 to May 2019.
The primary end point was least square mean change from baseline to week 48 in total body fat mass (FM); secondary and exploratory end points were lean mass (LM), waist circumference (WC), HbA1c level, and body weight (BW) changes from baseline to week 48.
At the end of the 48-week study, researchers found a nearly 21 percent decrease in body fat in the Bimagrumab group compared to 0.5 percent in the placebo group. The results also revealed the Bimagrumab group gained 3.6 percent of lean mass compared with a loss of 0.8 percent in the placebo group. The combined loss in total body fat and gain in lean mass led to a net 6.5 percent reduction in body weight in patients receiving Bimagrumab compared with 0.8 percent weight loss in their counterparts receiving the placebo.
The sample size of 75 participants was a limitation of the study. There was also a gender imbalance across the groups with more women randomized to Bimagrumab and more men to the placebo.
The the double-blinded, placebo-controlled study showed that bimagrumab treatment over 48 weeks was safe and well tolerated. The treatment reduced body fat and weight while increasing lean body mass (LBM). At week 48, fat mass decreased 21% (7.5 kg) in bimagrumab- vs. 0.5% (0.2 kg) in placebo-treated subjects (p<0.001) and HbA1c decreased 0.76% points in the bimagrumab group vs. an increase of 0.04% points in the placebo group (p=0.005).
Weight decreased 6.5% (5.9 kg) in bimagrumab- vs. 0.8% (0.8 kg) in placebo-treated subjects (p<0.001); LBM increased 3.6 % (1.7 kg) in the bimagrumab group vs. a decrease of 0.8% (0.4 kg) in the placebo group (p<0.001); and BMI was reduced 6.7% (2.2 kg/m2) in the bimagrumab group vs. 0.8% (0.3 kg/m2) in the placebo group (p<0.001).
“In this study, 48 weeks of exposure to bimagrumab, an antibody inhibitor of ActRII, was safe and effective for treating the excess adiposity and metabolic disturbances of adult patients with obesity and type 2 diabetes,” the authors concluded. “While antibody blockade or knockout of ActRII in animal models is accompanied by marked increases in skeletal muscle mass, this study confirms that inhibition of this receptor in human participants leads to not only increases in lean mass but profound decreases in body fat, along with improvements in glycemic control. Inhibition of ActRII may provide a novel pathway for the pharmacologic management of excess adiposity and accompanying metabolic disturbances.”
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