Lilly Halts Development of Oral GLP-1 Receptor Agonist Naperiglipron (LY3549492) for Obesity and Type 2 Diabetes

Sep 01, 2025 09:58 CST Updated 09:58

Eli Lilly

Global Pharmaceutical R&D and Production Company

｜Edited by the Content Team of Zhong Peptide Biochemical

2025Year August29DayEli Lilly Terminates Two Phase II Clinical Trials of Small Molecule GLP-1 Receptor Agonist Naperiglipron (LY3549492) for Obesity and Type 2 Diabetes with Obesity, Citing Business Strategy Reasons.

AboutNaperiglipron（LY3549492）

LY3549492 is a small moleculeGLP-1 Receptor Agonist: Its mechanism of action is similar to traditional GLP-1 class drugs, capable of precisely activating the GLP-1 receptor, thereby effectively regulating blood glucose and suppressing appetite. However, its unique advantage lies in achieving receptor activation without relying on a peptide structure, marking a breakthrough in drug development. Clinical trial results have been remarkable. In the ACHIEVE-1 Phase III trial targeting patients with type 2 diabetes, after 40 weeks of treatment, glycated hemoglobin (A1C) significantly decreased from a baseline of 8.0%, with an average reduction of 1.3% - 1.6%. In the highest-dose group, over 65% of patients successfully achieved A1C levels ≤6.5%, and patients in the high-dose group (36mg) experienced an average weight loss of 7.9%. In the ATTAIN-2 study targeting obese or overweight patients with type 2 diabetes, at 72 weeks, the 36mg highest-dose group showed an average weight reduction of up to 10.5% (10.4kg), with A1C decreasing by an average of 1.8%. The drug also played a positive role in improving cardiovascular risk factors such as non-high-density lipoprotein cholesterol and systolic blood pressure.

In terms of safety, the adverse reactions of Naperiglipron are generally consistent with GLP-1 class drugs, mainly presenting as mild to moderate gastrointestinal reactions, such as nausea, vomiting, and diarrhea. In the ATTAIN-2 study, the treatment discontinuation rate due to adverse events in the highest dose group was 10.6%, with no liver safety risks identified. Additionally, it is not restricted by food or water intake, significantly enhancing patient compliance.

AboutEli Lilly

Eli Lilly and Company is a pharmaceutical company dedicated to improving human health through scientific innovation and benefiting patients worldwide. As a leader in the healthcare industry, Eli Lilly and Company has nearly 150 years of history. Today, our medicines have helped tens of millions of people around the world. Harnessing the power of biotechnology, chemistry, and genomic medicine, our scientists are actively advancing new medical breakthroughs to address severe global health challenges. Redefining therapies for diabetes and obesity, reducing the long-term impact of obesity on the body; supporting prevention and treatment efforts for Alzheimer's disease; providing solutions for a range of immune-mediated diseases that threaten human health; and transforming difficult-to-treat cancers into manageable conditions.

ResourcesSource:

1. Medical Notes