Monthly GLP-1 shows strong weight loss in phase 2b trials

Clinical Takeaway: Berobenatide, an investigational ultra-long-acting GLP-1 receptor agonist, produced robust weight loss and glycemic improvements with low rates of gastrointestinal discontinuation, supporting ongoing phase 3 evaluation of monthly maintenance dosing.

If approved, berobenatide could become the first once-monthly GLP-1 receptor agonist, potentially improving long-term treatment adherence while maintaining clinically meaningful efficacy.

At the ADA 2026 Scientific Sessions, Pfizer presented phase 2b results from the VESPER clinical program evaluating berobenatide (PF-3944), a potential first-in-class monthly GLP-1 receptor agonist for obesity and overweight. Across studies in participants with and without type 2 diabetes, the agent demonstrated substantial weight loss with a favorable tolerability profile despite rapid dose escalation.

In a 32-week extension of the VESPER-1 trial, participants receiving the highest weekly dose (2.4 mg) achieved a mean non-placebo-adjusted weight loss of 15.9%, with no evidence of a weight-loss plateau at 32 weeks. In the VESPER-3 study, weight loss continued after patients transitioned from weekly to monthly dosing, with placebo-adjusted reductions of up to 12.3% at week 28. All tested monthly-dose regimens met the primary efficacy endpoint.

Among participants with obesity or overweight and type 2 diabetes in VESPER-2, berobenatide produced dose-dependent reductions in both body weight and glycemia. The 1.6 mg weekly dose achieved a 2.2-percentage-point reduction in HbA1c at week 28 compared with a 0.2-point reduction with placebo.

“These data highlight the potential for berobenatide to be the first approved monthly GLP-1 RA peptide,” said Jim List, MD, PhD, Pfizer’s Chief Internal Medicine Officer. Independent investigator John Buse, MD, PhD, added that the therapy has the potential to be “effective, but practical and sustainable in real life.”

Pfizer has launched an extensive phase 3 program for berobenatide, including studies in obesity and obesity-related comorbidities such as obstructive sleep apnea and knee osteoarthritis.

Source: Pfizer Inc. Robust Phase 2b Efficacy and Favorable Tolerability Support Monthly Dosing for Pfizer’s GLP-1 RA Berobenatide. Presented at the American Diabetes Association (ADA) 86th Scientific Sessions; June 6, 2026.