Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals

Diabetes Obes Metab. 2018 Jan;20(1):94-102. doi: 10.1111/dom.13042. Epub 2017 Aug 2.

Abstract

Aim: To test the hypothesis that an improving body composition in insulin-resistant individuals could enhance insulin sensitivity.

Methods: A total of 16 people with a mean body mass index of 29.3 kg/m2 and insulin resistance, received a single dose of bimagrumab or placebo and were assessed at week 10 for insulin sensitivity, using a hyperinsulinaemic-euglycaemic clamp and an intravenous glucose tolerance test (IVGTT), and for body composition using dual energy X-ray absorptiometry and positron-emission tomography.

Results: Bimagrumab increased lean mass by 2.7% (P < .05) and reduced fat mass by 7.9% (P = .011) at week 10 compared with placebo, and had a neutral effect on body weight. Bimagrumab reduced glycated haemoglobin by 0.21% at week 18 (P < .001) and improved insulin sensitivity by ~20% (according to the clamp) to ~40% (according to the IVGTT).

Conclusion: Taking the observed changes together, and given that these occurred without accompanying dietary intervention and without any prescribed regular physical exercise, bimagrumab may offer a novel approach for the treatment of the metabolic complications of obesity.

Keywords: HbA1c; activin receptor II; bimagrumab; body composition; insulin resistance; obesity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Absorptiometry, Photon
  • Adipose Tissue, Brown / diagnostic imaging
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adiposity / drug effects*
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / pharmacokinetics
  • Anti-Obesity Agents / therapeutic use*
  • Antibodies, Blocking / administration & dosage
  • Antibodies, Blocking / adverse effects
  • Antibodies, Blocking / therapeutic use*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Body Mass Index
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glucose Clamp Technique
  • Glucose Intolerance / blood
  • Glucose Intolerance / complications
  • Glucose Intolerance / drug therapy*
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Infusions, Intravenous
  • Insulin Resistance*
  • Male
  • Obesity / complications
  • Obesity / diagnostic imaging
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Pilot Projects
  • Positron Emission Tomography Computed Tomography
  • Thermogenesis / drug effects

Substances

  • Anti-Obesity Agents
  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • bimagrumab