February 26, 2026

expert reaction to ACHIEVE-3 trial results about efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes

Trial results published in The Lancet looks at the efficacy and safety of a once daily-daily oral pill (Orforglipron) compared to semaglutide. 

Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:

“These are important findings. The more effective oral medicines we have to help people with type 2 diabetes lose weight and keep it off, the better. Excess weight is the major driver of type 2 diabetes, and it also contributes to higher blood pressure and abnormal lipid levels.

“In this study, both orforglipron and oral semaglutide improved blood pressure and blood lipids, with slightly greater reductions observed with orforglipron – likely reflecting its stronger weight‑loss effect. It is worth noting, however, that the dose of oral semaglutide used here was relatively modest. Higher doses are now approved for weight management and are expected to be tested in people with diabetes as well.

“Currently, oral semaglutide has the advantage of proven cardiovascular benefit, whereas similar evidence for orforglipron is not yet available. Ongoing trials should provide clarity soon.

“Overall, the field is moving toward treatments that meaningfully improve weight, blood sugar, and cardiovascular risk at the same time. These more holistic approaches, which also benefit patient well-being, are likely to offer the greatest benefits for people living with type 2 diabetes. Indeed, we have suggested recently that incretin‑based therapies associated with considerable intentional weight loss may well become first‑line treatments for type 2 diabetes within the next decade, potentially helping many people achieve remission for several years.”

‘Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial’ by Julio Rosenstock et al. was published in The Lancet at 11:30am UK time on Thursday 26^th February 2026. 

DOI: https://doi.org/10.1016/S0140-6736(26)00202-3

Declared interests

Prof Naveed Sattar: “NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Kailera, Mass Medicines, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, UCB Pharma and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche.  No shares in any medical areas.”