Berobenatide Monthly Dosing Shows Weight Loss Efficacy in VESPER Trials, With John Buse, MD, PhD

VESPER-1 and VESPER-3 findings highlight the potential of berobenatide, an investigational ultra-long-acting GLP-1 RA, for overweight or obesity with or without type 2 diabetes.

New data presented at the 2026 Scientific Sessions of the American Diabetes Association (ADA) support the potential of berobenatide, an investigational ultra-long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), as a monthly injectable option for individuals with overweight or obesity with or without type 2 diabetes.¹

Results from the VESPER-1 open-label extension (OLE) and VESPER-3 phase 2b trials arrive as monthly administration draws increased attention in obesity pharmacotherapy as a meaningful departure from weekly injection schedules standard to currently approved GLP-1 RAs, with potential implications for adherence, healthcare system logistics, and treatment cost.

Berobenatide Efficacy and Design in VESPER-1 OLE and VESPER-3

VESPER-1 enrolled adults with overweight accompanied by hypertension or dyslipidemia, or with obesity, randomized to various berobenatide doses in a double-blind, placebo-controlled phase 2b design. The ADA presentation focused on the OLE, which defined a new maximum dose of 9.6 mg monthly for phase 3 advancement and demonstrated a transition from weekly to monthly dosing without significant added tolerability burden.¹

VESPER-3, a separate phase 2b trial in adults with overweight or obesity without type 2 diabetes, showed placebo-adjusted weight loss of up to 12.3% with the 4.8 mg monthly dose at 28 weeks, with a safety profile consistent with the GLP-1 RA class.¹

Berobenatide Monthly Dosing Rationale, Clinical Context

"Berobenatide is a potentially important new option for people living with overweight or obesity, especially because a once-monthly dosing could offer a more manageable alternative to today's more frequent injections," said John Buse, MD, PhD, lead author of the VESPER presentations.

In an interview, Buse elaborated on the layered rationale behind monthly dosing: for patients, 12 or 13 injections per year versus 52 represents a straightforward convenience gain. For providers and health systems, monthly administration opens the door to clinic- or nurse-administered dosing for patients with injection reluctance or severe dexterity limitations.

Buse also emphasized the economic dimension, noting monthly delivery dramatically reduces packaging and shipping demands, a consideration central to Metsera's original design goals for the drug.

"From start to finish, the drug is designed to provide value to patients and to healthcare systems, and the monthly dosing is part of that strategy," he said.

VESPER-3's final analysis will follow 64 weeks of exposure; longer-term data remain pending. A third phase 2b study, VESPER-2, extended findings to individuals with type 2 diabetes, demonstrating an encouraging risk-benefit profile. Data from all 3 phase 2b studies are informing the design of the phase 3 VESPER-4 and VESPER-6 trials.¹

Editors’ note: Buse reports relevant disclosures with Corcept, Dexcom, GentiBio, Novo Nordisk, Amgen, AstraZeneca, Boehringer-Ingelheim, Corcept Therapeutics, and others.

References

1. Buse J. Long-Term Treatment with the Ultra-Long-Acting GLP-1 Receptor Agonist MET-097 (PF-08653944) in Adults with Obesity or Overweight: The VESPER-1 Open-Label Extension. Presented at: American Diabetes Association 2026 Scientific Sessions; June 6, 2026; New Orleans, LA.

2. Buse J. Monthly Dosing of MET-097 (PF-08653944) for Weight Management: Primary Outcomes of the VESPER-3 Phase 2 Trial. Presented at: American Diabetes Association 2026 Scientific Sessions; June 6, 2026; New Orleans, LA.

3. ADA. Ultra-long-acting injectable GLP-1 RA shows promise for supporting weight management in individuals with and without type 2 diabetes. Published 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