Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 33439265 · doi:10.1001/jamanetworkopen.2020.33457
What was done
A double-blind, placebo-controlled, 48-week phase 2 randomized clinical trial was conducted at 9 sites in the US and UK involving 75 adults with type 2 diabetes, BMI between 28 and 40, and HbA1c between 6.5% and 10.0%. Participants received intravenous infusions every 4 weeks for 48 weeks of either bimagrumab (10 mg/kg up to 1200 mg; n = 37) or placebo (n = 38), alongside diet and exercise counseling. The primary endpoint was least-squares mean change in total body fat mass; secondary endpoints included changes in lean mass, waist circumference, HbA1c, and total body weight.
What was found
Of 75 randomized patients, 58 (77.3%) completed the 48-week trial. Compared to placebo, bimagrumab resulted in statistically significant improvements across all measured body composition and glycemic outcomes: - Total body fat mass: -20.5% (-7.5 kg [80% CI, -8.3 to -6.6 kg]) vs -0.5% (-0.18 kg [80% CI, -0.99 to 0.63 kg]; P < .001). - Lean mass: +3.6% (+1.70 kg [80% CI, 1.1 to 2.3 kg]) vs -0.8% (-0.4 kg [80% CI, -1.0 to 0.1 kg]; P < .001). - Waist circumference: -9.0 cm (80% CI, -10.3 to -7.7 cm) vs +0.5 cm (80% CI, -0.8 to 1.7 cm; P < .001). - HbA1c level: -0.76 percentage points (80% CI, -1.05 to -0.48) vs -0.04 percentage points (80% CI, -0.23 to 0.31; P = .005). - Body weight: -6.5% (-5.9 kg [80% CI, -7.1 to -4.7 kg]) vs -0.8% (-0.8 kg [80% CI, -1.9 to 0.3 kg]; P < .001).
Why it matters
Activin type II receptor inhibition with bimagrumab provides a novel pharmacological approach for body composition management, achieving substantial fat loss while simultaneously increasing lean muscle mass and improving glycemic control.
Limits
The trial had a small sample size (n = 75 randomized, n = 58 analyzed) and excluded non-completers from the analysis rather than using an intention-to-treat approach. There was a notable baseline sex imbalance between groups (62.2% women in the bimagrumab group vs 31.6% in the placebo group). Results reported 80% confidence intervals rather than conventional 95% intervals, and specific adverse event frequencies and drop-out reasons were not detailed in the abstract.
Cited by
- supports Bimagrumab binds to activin receptors to inhibit the myostatin pathway and preserve muscle mass.