Glucagon Receptor Antagonist: a Diabetes Drug Development

Glucagon and insulin work in concert to achieve and maintain proper blood glucose levels. Glucagon, released by pancreatic alpha cells, prevents hypoglycemia, while insulin released by beta cells prevents hyperglycemia. Together they preserve a tight blood glucose concentration between 70-100 mg/dL fasting and 70-140 mg/dL after meals. In type 2 diabetes, glucagon production, release, and action are malfunctioning. Overproduction of glucagon leads to over-stimulation of gluconeogenesis and glycolysis, exacerbating hyperglycemia in diabetes mellitus.

Naturally, efforts to reduce glucagon synthesis, secretion, or effects are pursued. During this phase-2 clinical trial, researchers investigated the efficacy of a glucagon receptor antagonist in reducing A1c levels in 166 patients with metformin-uncontrolled type 2 diabetes over 12 weeks. The glucagon receptor antagonist RVT-1502, at the high dose of 15 mg per day, lowered A1c by 1.0% without inducing severe hypoglycemia. Slight elevations in aminotransferases and blood pressure were documented, respectively.

Given the meaningful positive results of the study, a follow-up phase-3 randomized clinical trial would be expected.

Dr. Tashko