The first small-molecule glucagon-like peptide 1 receptor agonist to complete a phase 3 trial lowers A1c and reduces weight, the company says.
Orforglipron, Eli Lilly's investigational oral glucagon-like peptide 1 receptor agonist (GLP-1 RA), achieved positive phase 3 results for both A1c and weight loss, according to top-line data released by the company. The findings came from Lilly's ACHIEVE-1, the first of seven phase 3 trials examining the safety and efficacy of orforglipron in over 6000 patients with diabetes and obesity. Full results will be presented on June 2025 at the American Diabetes Association (ADA) 85th Scientific Sessions and will be published in a peer-reviewed journal. Orforglipron is a once-daily nonpeptide small molecule that can be taken any time of day without restrictions on meals or water intake. This contrasts with the currently approved oral GLP-1 RA semaglutide (Rybelsus, Novo Nordisk), a peptide which ideally should be taken fasting and with no food or water for at least 30 minutes after ingestion to prevent degradation. Asked to comment on the new top-line data, independent consultant Charles M. Alexander, MD, told Medscape Medical News that the results are "Great news for Lilly. A pill taken daily is going to be much easier for patients compared to injections, even once-weekly injections. A1c and weight loss were at least as good as semaglutide phase 3 type 2 diabetes data, if not a little bit better." However, Alexander added, "We need a head-to-head study to really understand both comparative efficacy and safety. What is the price going to be? The presentation at ADA and the publication…will help fill in the gaps not included in the top-line results." In a statement from the UK Science Media Centre, Naveed Sattar, MD, professor of cardiometabolic medicine/honorary consultant, University of Glasgow, Glasgow, Scotland, said, "These are important results. Having new oral agents that lower glucose but also meaningfully lower weight well beyond levels seen with most existing diabetes…