Background

Both fat and lean body mass (LBM) decline with weight loss. We explored the safety and efficacy of bimagrumab on body composition and glycemic control in overweight and obese adults with type 2 diabetes (T2D).

Methods

In this double-blinded, placebo-controlled study, 75 adults with BMI 28-40 kg/m2 and HbA1c 6.5-10.0% were randomized to either bimagrumab, 10 mg/kg up to a maximum of 1200 mg i.v., or placebo, every 4 weeks for 48 weeks. All subjects received diet and exercise counseling. Key endpoints were change from baseline to week 48 in total fat mass measured by DXA (primary), HbA1c, weight and LBM.

Results

58/74 (77.3%) participants (mean age 60.4 yrs; 47% female) completed the study. Bimagrumab was safe and well tolerated. 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.

Conclusions

Bimagrumab treatment over 48 weeks was safe and well-tolerated, and reduced body fat and weight while increasing LBM in overweight and obese adults with T2D. Bimagrumab is the only treatment to demonstrate profound fat loss and weight loss while increasing LBM and improving metabolic status.