Pfizer announced positive topline results from the Phase IIb VESPER-3 trial evaluating its investigational, ultra-long-acting injectable GLP-1 receptor agonist PF-08653944 (also referred to as PF’3944) in adults with obesity or overweight without type 2 diabetes, with the study meeting its primary endpoint of statistically significant placebo-adjusted weight reduction at week 28.
Pfizer states that the data showing continued weight loss after switching from weekly to monthly dosing support advancing once-monthly administration in larger trials and contribute to Pfizer’s broader obesity development program.
Trial specifics
VESPER-3 is an ongoing 64-week, randomized, double-blind, placebo-controlled Phase IIb study designed to assess once-monthly maintenance dosing of PF-08653944 after an initial weekly titration phase. Participants with obesity or overweight without type 2 diabetes received sequential weekly injections for 12 weeks followed by monthly subcutaneous injections to week 28 under one of four titration protocols, compared with placebo, with weight change from randomization to week 28 as the primary endpoint.
The study demonstrated statistically significant placebo-adjusted weight loss in all PF-08653944 arms, with up to 12.3% mean weight reduction at week 28 without evidence of a plateau, suggesting continued benefit as dosing frequency reduced. The safety profile was consistent with the GLP-1 receptor agonist class and a comparable number of discontinuations due to adverse events in both weekly and monthly segments. Pfizer will present detailed data at the American Diabetes Association Scientific Sessions in June 2026.
Pfizer acquired PF-08653944 via the purchase of Metsera, and is planning on 10 Phase III trials for the molecule in 2026, encompassing combinations of weekly and monthly regimens as well as studies in people with and without type 2 diabetes. The company also has a collaboration and license with YaoPharma supporting broader obesity pipeline initiatives across peptide mechanisms.
Research context
PF-08653944 is a fully biased glucagon-like peptide-1 (GLP-1) receptor agonist formulated for extended duration to enable once-monthly subcutaneous injection, distinguishing it from established weekly GLP-1 therapies. GLP-1 receptor agonists enhance insulin secretion, suppress glucagon, slow gastric emptying, and promote satiety, making them foundational in obesity and type 2 diabetes treatment.