Pfizer announced positive Phase 2b VESPER-3 topline results for its monthly injectable GLP-1 receptor agonist PF’3944, showing up to 12.3% placebo-adjusted weight loss at week 28 in adults with obesity or overweight.
Written By: Pharmacally Medical News Desk
Pfizer Inc. has reported positive topline results from the Phase 2b VESPER-3 study evaluating its ultra-long-acting injectable GLP-1 receptor agonist PF’3944 (PF-08653944; previously MET-097i) as a monthly maintenance treatment for adults with obesity or overweight without type 2 diabetes. The trial was designed to test whether patients could transition from weekly injections to a once-monthly regimen while maintaining efficacy and tolerability.
The study met both primary objectives. PF’3944 delivered statistically significant and clinically meaningful weight reduction after switching from weekly titration to monthly dosing. At week 28, participants achieved up to 12.3% mean placebo-adjusted weight loss, with all four active dose regimens demonstrating superiority over placebo (P < 0.001). Pfizer noted that weight loss remained continuous with no plateau observed at the interim analysis, suggesting further reductions may occur as the study continues through week 64.
VESPER-3 Trial Design and Results
VESPER-3 is 64-week, randomized, double-blind, placebo-controlled trial enrolling participants with obesity or overweight. Patients were assigned to four titration and maintenance dosing strategies that began with weekly injections until week 12, followed by monthly administration through week 28. The study included approximately 54 participants per arm. The low and medium monthly maintenance regimens planned for Phase 3 showed strong efficacy, achieving 10% and 12.3% placebo-adjusted weight loss in Arms 1 and 3, respectively.
Safety Profile
PF’3944 also maintained a favorable safety profile consistent with the GLP-1 receptor agonist class. Gastrointestinal adverse events were mostly mild or moderate, with no severe diarrhea reported and only one instance of severe nausea or vomiting in any dose group. Discontinuations due to adverse events were limited, with five participants stopping during the weekly phase and five during the monthly phase across Arms 1 and 3, while no placebo participants discontinued treatment for adverse events.
“These topline results from the Phase 2b VESPER-3 study reinforce the potential of PF’3944 as a monthly treatment with competitive efficacy,” said Jim List, MD, PhD, Chief Internal Medicine Officer at Pfizer. He added that the company remains confident in advancing higher-dose monthly maintenance regimens, including a planned 9.6 mg dose, into Phase 3 development.
Pfizer’s Obesity Pipeline Expansion
The results further strengthen PF’3944 as a central component of Pfizer’s expanding obesity pipeline. Following its acquisition of Metsera and a global collaboration and licensing agreement with YaoPharma, Pfizer has built a broad portfolio of clinical-stage injectable and oral obesity therapies. These programs target not only GLP-1 but also GIP receptor pathways and amylin analogs.
Pfizer plans an extensive obesity development strategy in 2026, with more than 20 trials expected to advance. This includes 10 Phase 3 studies of PF’3944, such as the ongoing VESPER-4 trial investigating once-weekly dosing in patients without diabetes, the planned VESPER-5 trial in patients with type 2 diabetes, and the planned VESPER-6 study evaluating once-monthly PF’3944 in obesity and overweight. Additional Phase 3 trials are expected to explore comorbidities and expand treatment options.
PF’3944 is described as a fully biased, ultra-long-acting GLP-1 receptor agonist being developed both as a standalone weekly or monthly therapy and as part of combination approaches. Pfizer is also exploring PF’3944 in combination with other investigational peptides, including the amylin analog PF’3945 (PF-08653945; MET-233i) and the GIPR agonist PF-08654696 (MET-034i).
Detailed findings from the VESPER-3 study will be presented on June 6, 2026, at the 86th Scientific Sessions of the American Diabetes Association, providing further insight into the potential of monthly GLP-1 therapy to improve long-term obesity management.
References
Pfizer’s Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial, 03 February 2026, Pfizer’s Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial | Pfizer
A Phase 2b Study to Evaluate the Efficacy and Safety of Once-Monthly MET097 in Adults with Obesity or Overweight (VESPER-3), ClinicalTrials.gov ID NCT06973720, https://clinicaltrials.gov/study/NCT06973720