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

Garito, Tania and Roubenoff, Ronenn and Zakaria, Marjorie and Rooks, Daniel and Swan, Therese and Filosa, Lee Anne and Petricoul, Olivier and Laurent, Didier and Neelakantham, Srikanth Raju and Meyers, Charles and Hompesch, Marcus and morrow, linda and gomez, katherine and buchsbaum, monte (2017) Bimagrumab improves body composition and insulin sensitivity in insulin-resistant subjects. Diabetes, obesity and metabolism. ISSN 1463-1326

Abstract

Background: Skeletal muscle is a key mediator of insulin resistance. Bimagrumab, an antibody against activin receptor type II (ActRII), prevents binding of negative muscle regulators, like myostatin, and increases lean mass and decreases fat mass in animal models.
Objective: We hypothesized that an improving body composition in insulin resistant individuals could enhance insulin sensitivity.
Methods: Sixteen individuals with mean body mass index (BMI)=29.3 kg/m2 and insulin resistance, received a single dose of bimagrumab or placebo and were assessed at Week 10 for insulin sensitivity, with hyperinsulinemic euglycemic (H-E) clamp and intravenous glucose tolerance test (IVGTT), and for body composition, with dual energy X-ray absorptiometry (DXA) and Positron emission tomography (PET) scan.
Results: Bimagrumab increased lean mass by 2.7% (p<0.05) and reduced fat mass by 7.9% (p=0.011) at Week 10 compared to placebo, with a neutral effect on body weight. Bimagrumab reduced HbA1c by 0.21% at Week 18 (p<0.001) and improved insulin sensitivity by ~20% (using the clamp) to ~40% (using the IVGTT).
Conclusion: Taken the observed changes together and in consideration that these occurred without accompanying dietary intervention and without any prescribed regular physical exercise, bimagrumab may offer a novel approach for the treatment of metabolic complications of obesity.

Item Type: Article
Date Deposited: 22 Aug 2017 00:45
Last Modified: 22 Aug 2017 00:45
URI: https://oak.novartis.com/id/eprint/33453

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