Investigational oral GLP-1 drug lowers A1c, weight in phase 3 trial

Eli Lilly's investigational oral GLP-1 receptor agonist, orforglipron, is the first small molecule GLP-1 to successfully complete a phase 3 trial, demonstrating similar efficacy to injectable GLP-1 therapies. The phase 3 ACHIEVE-1 trial (NCT05971940) included 559 adults with T2DM, an average baseline HbA1c of 8.0%, and a baseline weight of 198.9 lbs. Participants were randomly assigned to receive orforglipron 3mg, 12mg, 36mg, or placebo once daily. Orforglipron significantly reduced HbA1c levels by 1.3% to 1.6% over 40 weeks, with more than 65% of those on the highest dose achieving HbA1c levels ≤6.5%. Additionally, orforglipron led to an average weight loss of 16.0 lbs (7.9%) at the highest dose. The safety profile was consistent with injectable GLP-1 therapies, with no significant adverse events reported. Eli Lilly announced plans to submit orforglipron to FDA for approval as a T2DM treatment in 2026.

Sources:

(2025, April 17). Eli Lilly and Company. Lilly's oral GLP-1, orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial. [News release]. https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically

Lovelace, Jr., B, et al. (2025, April 17). NBC News. Lilly says daily pill can lower blood sugar and weight in people with Type 2 diabetes. https://www.nbcnews.com/health/health-news/lilly-says-daily-pill-can-lower-blood-sugar-weight-people-type-2-diabe-rcna201605

Moniuszko, S. (2025, April 17). CBS News. Eli Lilly says GLP-1 pill for diabetes and weight loss effective in study, plans to seek FDA approval. https://www.cbsnews.com/news/eli-lilly-glp-1-pill-trial-fda-approval/