Pfizer has reported positive topline results from its Phase 2b VESPER-3 trial evaluating PF-08653944 (PF’3944; MET-097i), an ultra-long-acting injectable GLP-1 receptor agonist, in adults with obesity or overweight without type 2 diabetes.
The study met its primary endpoint, demonstrating statistically significant weight reduction at 28 weeks with a favourable safety and tolerability profile. Patients continued to lose weight after switching from weekly to monthly dosing, with no plateau observed at week 28, supporting the potential of a once-monthly treatment regimen.
At week 28, PF’3944 achieved up to 12.3% mean placebo-adjusted weight loss, with all four active dose regimens showing superiority over placebo (P < 0.001). The trial included a weekly titration phase through week 12, followed by monthly maintenance dosing through week 28. Results suggest that efficacy was maintained despite a four-fold reduction in dosing frequency.
The ongoing 64-week, randomized, double-blind, placebo-controlled study enrolled participants across five arms, including four titration and monthly dose regimens and one placebo arm, with approximately 54 participants per group. Arms 1 and 3—representing the low and medium monthly maintenance doses planned for Phase 3—achieved 10% and 12.3% placebo-adjusted weight loss, respectively. Continued weight loss is expected as the study progresses to week 64.
PF’3944 demonstrated a safety profile consistent with the GLP-1 class, with gastrointestinal adverse events largely mild to moderate. There were no reports of severe diarrhoea and no more than one instance of severe nausea or vomiting in any treatment group. Treatment discontinuations due to adverse events were limited, with none reported in the placebo arm.
Detailed VESPER-3 results will be presented on June 6, 2026, at the 86th Scientific Sessions of the American Diabetes Association.
Pfizer plans to advance an extensive Phase 3 development programme in 2026, including 10 Phase 3 trials of PF’3944evaluating weekly and monthly dosing in people with obesity or overweight, with and without type 2 diabetes, as well as studies targeting obesity-related comorbidities. More than 20 clinical studies across Pfizer’s obesity pipeline are planned or underway.
PF’3944 is an ultra-long-acting, fully biased GLP-1 receptor agonist, being developed as both a weekly and monthly injectable therapy and in combination with other metabolic agents, including an amylin analog and a GIP receptor agonist. The candidate forms a central component of Pfizer’s obesity pipeline following its acquisition of Metsera and collaboration with YaoPharma.
Obesity remains a major global health challenge, affecting an estimated 1.9 billion people worldwide and projected to exceed 2.9 billion by 2030, underscoring the need for therapies that improve efficacy, tolerability, adherence and long-term outcomes.
