Orforglipron — First Oral Non-Peptide GLP-1 RA Phase 3 ACHIEVE Program

Type: drug

Status: Active — ACHIEVE Program

Developer: Eli Lilly

Breakthrough Summary

Orforglipron is a small molecule oral GLP-1 RA that does not require fasting or water restrictions before dosing, unlike oral semaglutide. Phase 2 data showed HbA1c reductions of -1.6% and weight loss of -10.1% at 36 weeks. The ACHIEVE Phase 3 program evaluates T2D glycemic control, obesity, and CV outcomes.

Mechanism of Action

Non-peptide small molecule that binds and activates the GLP-1 receptor. Unlike peptide-based GLP-1 RAs, it is resistant to gastrointestinal degradation without requiring absorption enhancers or fasting conditions.

Year: 2025-2026