Pfizer Phase IIb Data Support Monthly GLP-1 Dosing for Obesity

Pfizer reported positive topline results on Feb. 3, 2026 from a Phase IIb trial (VESPER-3) evaluating monthly maintenance dosing of its ultra-long-acting injectable glucagon-like peptide 1 (GLP-1) receptor agonist, PF-08653944 (PF’3944, also known as MET-097i), in adults with obesity or overweight without type 2 diabetes. The data add to growing evidence that extended-interval dosing may offer a viable alternative to weekly GLP-1 regimens while maintaining clinically meaningful weight loss and tolerability (1).

VESPER-3 met its primary endpoint, demonstrating statistically significant placebo-adjusted weight reduction at 28 weeks across all tested dose regimens. According to Pfizer, the study also showed continued weight loss after a planned transition from weekly to monthly dosing, with no plateau observed at the interim analysis, supporting further development of monthly maintenance strategies (1).

“These topline results from the [Phase IIb] 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, Pfizer, in a company press release

Can monthly GLP-1 dosing sustain weight loss without compromising efficacy?

The ongoing, randomized, double-blind, placebo-controlled VESPER-3 study was designed to assess whether PF’3944 could maintain efficacy while reducing injection frequency four-fold. Participants underwent weekly titration through week 12 before switching to monthly dosing through week 28, with follow-up planned through 64 weeks (1).

At week 28, placebo-adjusted mean weight loss reached up to 12.3%. In the two dose arms selected for Phase III development, placebo-adjusted weight loss reached 10% and 12.3%, respectively. Importantly, weight reduction continued after the transition to monthly dosing, suggesting that longer-acting GLP-1 formulations may avoid early efficacy plateaus observed in some chronic weight-management therapies (1).

Pfizer noted that detailed results from the study are scheduled to be presented at the American Diabetes Association Scientific Sessions on June 6, 2026.

How does tolerability compare with established GLP-1 therapies?

PF’3944 maintained a safety and tolerability profile consistent with the GLP-1 receptor agonist class through week 28, according to the trial results (1). Gastrointestinal treatment-emergent adverse events were predominantly mild or moderate, with no more than one severe nausea or vomiting event reported in any dose group and no cases of severe diarrhea.

“Based on the monthly dosing efficacy and tolerability demonstrated in this trial, we remain confident in our plan to include a higher 9.6 mg monthly maintenance dose of PF’3944 in [Phase III]. With PF’3944 as an anchor of Pfizer’s obesity pipeline, we are positioned to address critical gaps in obesity care and meet the diverse needs of patients,” Dr. List said in the release.

What does VESPER-3 signal for late-stage obesity drug development?

The VESPER-3 data arrive as Pfizer prepares a broad Phase III development program for PF’3944, with 10 Phase III trials expected to advance in 2026. The planned studies include weekly and monthly regimens across populations with and without type 2 diabetes, as well as trials designed to address obesity-related comorbidities.

PF’3944 is part of a broader obesity pipeline that includes injectable and oral candidates targeting GLP-1 and glucose-dependent insulinotropic polypeptide receptors, as well as amylin analogs. Together, these programs reflect an industry-wide push to diversify obesity treatment options beyond weekly injectables, with longer-acting agents positioned to improve convenience, persistence, and real-world effectiveness (2).

As competition intensifies in the GLP-1 space, VESPER-3 underscores how dosing flexibility and durability of response are becoming key differentiators in late-stage development.

References

1. Pfizer. Pfizer’s Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial. Press Relese. Feb. 3, 2026.
2. Melson, E.; Ashraf, U.; Papamargaritis, D.; et al. What is the Pipeline for Future Medications for Obesity? Int. J. Obes. 2025, 49, 433–451. DOI: 10.1038/s41366-024-01473-y