Comprehensive Report on LY-3537031: An Investigational Dual GIPR/GLP-1R Agonist

1. Executive Summary of LY-3537031

LY-3537031 is an investigational synthetic peptide currently under development by Eli Lilly and Company, positioned within the therapeutic area of endocrinology and metabolic diseases, with a primary focus on obesity.[1] The compound functions as a dual agonist for the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R).[1] This mechanism of action is well-established within Eli Lilly's portfolio, notably with the successful drug tirzepatide. LY-3537031 is administered subcutaneously and is recognized as a New Molecular Entity (NME), a designation that underscores its novelty and potential for market exclusivity upon approval.[2]

The clinical development program for LY-3537031 is in Phase 1. A single ascending dose (SAD) study, NCT04648865, conducted in healthy Japanese volunteers, has been completed.[1] A more extensive multiple ascending dose (MAD) study, NCT06606106, is currently recruiting participants, including overweight and obese individuals, as well as healthy volunteers from diverse ethnic backgrounds, including Japanese and Chinese cohorts.[1] This ongoing trial aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of LY-3537031, including its effects on body weight and gastric emptying. The development of LY-3537031, identified in Eli Lilly's pipeline as "GIP/GLP-1 Coagonist III" [6], signifies a continued strategic investment by the company in leveraging dual incretin agonism to address the significant unmet medical needs in obesity and related metabolic conditions.

2. Introduction to LY-3537031

Background and Rationale for Development in Obesity and Metabolic Diseases