Improved Postprandial Glucose Metabolism in Type 2 Diabetes by Dual Glucagon‐like Peptide‐1 / Glucagon Receptor Agonist SAR425899 in Comparison to Liraglutide

OBJECTIVE Dual glucagon-like peptide-1/glucagon receptor agonist (GLP-1/GCG RA) SAR425899 showed positive effects on glycemic control and reduction of body weight in overweight to obese patients with type 2 diabetes mellitus (T2D) after 4 weeks of treatment, with a safety profile comparable with GLP-1 RA. Here, we aim to give further insights into SAR425899 efficacy, by also providing direct comparison against the GLP-1 RA Liraglutide in terms of key parameters of glucose metabolism. RESEARCH DESIGN AND METHODS Seventy overweight to obese subjects with T2D were randomized to receive once-daily subcutaneous administrations of SAR425899 (0.12 mg, 0.16 mg or 0.20 mg), Liraglutide (1.80 mg) or placebo for 26 weeks. Mixed meal tolerance tests (MMTT) were conducted at baseline (BSL) and at the end of treatment (EOT). Metabolic indices of insulin action and secretion were assessed via Homeostasis Model Assessment (HOMA2) and oral minimal model (OMM) methods. RESULTS From BSL to EOT (Median [25th ,75th ]percentile), HOMA2 quantified a significant improvement in basal insulin action in Liraglutide (35 [21,74]%), while secretion enhanced both in SAR42899 (125 [63,228]%) and Liraglutide (73 [43,147]%). OMM quantified, both in SAR425899 and Liraglutide, a significant improvement in insulin sensitivity (203 [58,440]% and 36 [21,197]%), basal β-cell responsiveness (67 [34,112]% and 40 [16,59]%), above-basal β-cell responsiveness (139 [64,261]% and 69 [-15,120]%). A significant delay in glucose absorption was highlighted in SAR425899 (37 [52,18]%). CONCLUSIONS SAR425899 and Liraglutide improved postprandial glucose control in overweight to obese subjects with T2D. A significantly higher enhancement in β-cell function was shown by SAR425899 than Liraglutide. This article is protected by copyright. All rights reserved.