HMN 2026: How New GLP-1 pill orforglipron outperforms oral semaglutide in yearlong diabetes trial

A novel GLP-1 receptor agonist (RA) pill called orforglipron leads to a larger reduction in blood sugar levels after a year than the current available oral GLP-1 RA (semaglutide), finds a phase 3 randomized controlled trial published in The Lancet. Additionally, participants taking orforglipron had significantly greater reductions in body weight than those taking oral semaglutide.

Currently, the only available oral GLP-1 RA is semaglutide, which must be taken on an empty stomach. Orforglipron is an alternative oral GLP-1 RA that can be taken with or without food and is currently under review with the FDA. ACHIEVE-3 is the first phase 3 trial to directly compare orforglipron (12 or 36 mg) with oral semaglutide (7 or 14 mg).

In the trial, over 1,500 people with type 2 diabetes from 131 medical research centers and hospitals in Argentina, China, Japan, Mexico, and the U.S. were randomized to take orforglipron at one of the two doses or semaglutide at one of two doses for a year.

The participants who took orforglipron had—on average—a greater drop in blood sugar levels for both doses than either of the doses of semaglutide. Patients, starting at an average weight of 97 kg, lost on average 6–8% of their weight with orforglipron and 4–5% with semaglutide. However, 9–10% of participants in the orforglipron groups stopped taking the pill due to adverse events (mostly gastrointestinal issues), compared to 4–5% in the semaglutide groups.

Authors say that orforglipron could be a new treatment option for people with type 2 diabetes who prefer a pill to an injection and do not want any restrictions on food and fluid intake.

The content is provided for information purposes only.