Adomeglivant (LY2409021): A Comprehensive Monograph on a Discontinued Glucagon Receptor Antagonist

1.0 Executive Summary

Adomeglivant, also known by its development code LY2409021, is a potent, selective, and orally bioavailable small-molecule antagonist of the human glucagon receptor (GCGR). Developed by Eli Lilly and Company, the compound was investigated as a novel therapeutic agent for the treatment of Type 2 Diabetes Mellitus (T2DM).[1] The therapeutic rationale was predicated on a direct and logical mechanism: by blocking the action of glucagon at its receptor in the liver, Adomeglivant was designed to suppress the excessive hepatic glucose production that is a hallmark of T2DM pathophysiology.

The clinical development program for Adomeglivant successfully validated this hypothesis. In Phase 2 clinical trials, the drug demonstrated robust, dose-dependent, and clinically meaningful efficacy, producing significant reductions in key glycemic parameters, including glycated hemoglobin (HbA1c), fasting serum glucose, and postprandial glucose levels.[2] The magnitude of glucose lowering was comparable to established oral antidiabetic agents, and notably, this was achieved with a minimal risk of hypoglycemia, a common and dangerous side effect of many diabetes therapies.