Berobenatide weight loss benefit maintained in shift to monthly dosing, phase 2b data show
Presenters: John B. Buse, MD, PhD, University of North Carolina School of Medicine, Chapel Hill, NC
The VESPER-1 OLE, -2 and -3 trials of berobenatide (MET-097, PF-08653944), an ultra-long-acting GLP-1 receptor agonist for weight management. Presented June 6, 2026.
Berobenatide, an investigational ultra-long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, continued to keep weight off when the dosing interval was stretched from once weekly to once monthly, according to phase 2b data presented at the American Diabetes Association (ADA) 2026 Scientific Sessions.
The finding was reported in an ADA symposium covering 3 trials in the VESPER program. Together, the studies have tested the drug across weekly and monthly dosing intervals in individuals with overweight or obesity, with and without type 2 diabetes.
Among those studies is VESPER-3, which evaluated a preplanned switch from weekly to monthly injections of the GLP-1 agent in adults without type 2 diabetes. In that scenario, berobenatide produced placebo-adjusted weight loss of up to 12.3% at 28 weeks, John B. Buse, MD, PhD, reported.
Other reports in the symposium covered a separate weekly trial, VESPER-2, which paired weight loss with glycemic improvement in adults who also had type 2 diabetes, and an open-label extension of VESPER-1 that tested the drug at its highest weekly dose.
Altogether, berobenatide could become an important option for people with overweight or obesity, particularly because once-monthly dosing may be more manageable than the more frequent injections used for other GLP-1 receptor agonists, according to Dr. Buse.
“For patients, this less-frequent dosing may help ease the burden of ongoing treatment and support better long-term adherence in chronic conditions like obesity and type 2 diabetes,” Dr. Buse said.
Obesity and diabetes raise the risk of serious conditions, including cardiovascular disease, and next-generation dosing strategies are designed to improve efficacy, simplify regimens, and reduce injection burden, according to an ADA news release discussing the VESPER program results.
VESPER-3: Switching from weekly to monthly doses
VESPER-3, presented by Dr. Buse, is an ongoing 64-week, randomized, double-blind, placebo-controlled study of berobenatide in adults with overweight or obesity without type 2 diabetes.
Participants were randomized to five groups of approximately 54 patients each, who received either one of four weekly-titration-to-monthly dose regimens of berobenatide or placebo, with weekly dosing through week 12 followed by monthly dosing to week 28.
The primary endpoint was weight reduction from randomization to week 28.
At week 28, patients had lost more weight with all four berobenatide regimens than with placebo (P < .001), with placebo-adjusted weight loss of up to 12.3% of body weight with the 4.8-mg monthly dose on the efficacy estimand, Buse reported.
No plateau in weight loss was observed at week 28, and tolerability was consistent with that of the GLP-1 receptor agonist class, with gastrointestinal adverse events that were predominantly mild or moderate, according to a news release describing the results.
The study's final endpoint will be assessed at 64 weeks.
VESPER-1 open-label extension
VESPER-1 evaluated once-weekly berobenatide over 28 weeks in adults with overweight or obesity, with an open-label extension that tested higher doses and different dosing schedules.
In a 32-week extension, participants who escalated from placebo to the top weekly dose of 2.4 mg achieved non-placebo-adjusted mean weight loss of 15.9%, with no plateau at 32 weeks, corresponding to week 60 of the overall study.
The analysis presented at ADA marked the first clinical experience with the highest weekly dose of berobenatide, according to a news release.
VESPER-2: Effects in patients with type 2 diabetes
VESPER-2, also presented at ADA, was a randomized, double-blind, placebo-controlled phase 2b trial of once-weekly berobenatide over 28 weeks in adults with overweight or obesity and type 2 diabetes.
Berobenatide produced dose-dependent reductions in both body weight and hemoglobin A1c, according to results of the study.
With the 1.6-mg weekly dose, hemoglobin A1c had fallen by 2.2 percentage points at week 28, compared with 0.2 percentage points in the placebo group, the data showed.
The results extended the drug's risk-benefit profile to people living with overweight or obesity and type 2 diabetes, according to a news release describing the results.
Weight management is a lifelong commitment, and the barriers to staying on therapy are as important as the therapy itself, Dr. Buse said.
Berobenatide has delivered meaningful weight loss with a well-tolerated profile after the switch from weekly to monthly dosing in the phase 2b studies, he noted, adding: “If approved, berobenatide has the potential to be not only effective, but practical and sustainable in real life.”
The three phase 2b studies informed the design and dosing regimens for later trials, including the phase 3 VESPER-4 and VESPER-6 studies, the authors noted.
Disclosures
Pfizer sponsored the VESPER studies of berobenatide that were presented at the ADA meeting.
References
American Diabetes Association. Ultra-long-acting injectable GLP-1 RA shows promise for supporting weight management in individuals with and without type 2 diabetes (news release). June 6, 2026. https://www.prnewswire.com/news-releases/ultra-long-acting-injectable-glp-1-ra-shows-promise-for-supporting-weight-management-in-individuals-with-and-without-type-2-diabetes-302793181.html. Accessed June 9, 2026.
American Diabetes Association 2026 Scientific Sessions. Symposium CT-SY25-1.5: The VESPER-1 OLE, -2 and -3 trials of berobenatide (MET-097, PF-08653944), an ultra-long-acting GLP-1 receptor agonist for weight management. Presented June 6, 2026.
Pfizer Inc. Robust phase 2b efficacy and favorable tolerability support monthly dosing for Pfizer's GLP-1 RA berobenatide (news release). June 6, 2026. https://www.pfizer.com/news/press-release/press-release-detail/robust-phase-2b-efficacy-and-favorable-tolerability-support. Accessed June 9, 2026.