LY-3549492: An Investigational Oral GLP-1 Receptor Agonist for Metabolic Diseases

1. Executive Summary

LY-3549492 is an investigational small molecule drug candidate under development by Eli Lilly and Company. Administered orally, it is positioned as a potential treatment for Type 2 Diabetes Mellitus (T2DM) and obesity/overweight.[1] Based on available information, LY-3549492 functions as a Glucagon-like peptide-1 receptor (GLP-1R) agonist, placing it within the incretin mimetic class of therapeutics.[2] This mechanism involves mimicking the action of the endogenous GLP-1 hormone to improve glycemic control and promote weight loss.[3]

The highest stage of clinical development currently reported for LY-3549492 is Phase 2, with an active (though not recruiting) trial focused specifically on weight management in adults with obesity or overweight (NCT06683508).[2] Several Phase 1 trials have been completed, including studies in healthy volunteers (NCT06194500) and participants with T2DM (NCT05327595), likely assessing safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD).[2] A Phase 1 trial in Japanese participants with T2DM and healthy Japanese individuals (NCT06869018) is planned, indicating global development interest.[2]

The development of LY-3549492 as an oral small molecule represents a potentially significant advancement in a therapeutic area currently dominated by injectable peptide-based GLP-1R agonists. However, detailed efficacy, safety, preclinical findings, and specific intellectual property information are not available in the reviewed sources, making the forthcoming results from the Phase 2 trial critical for assessing its therapeutic potential and competitive positioning.

2. Introduction