VESPER-3: Positive Results of Long-Term GLP-1 PF’3944 in Overweight and Obesity Without T2D

PF’3944, Pfizer, Inc.’s investigational ultra-long-acting, fully biased GLP-1 receptor agonist (RA), has shown statistically significant weight reduction compared to placebo in patients with obesity or overweight without type 2 diabetes (T2D), according to data from the VESPER-3 phase 2b trial.1

VESPER-3 had 2 primary objectives, according to the new release: these were to demonstrate PF’3944’s efficacy in achieving continued weight loss after switching from weekly to monthly subcutaneous injections and reducing the dosing frequency 4-fold, and to demonstrate PF’3944’s capacity to switch to a 4-fold equivalent monthly dose while remaining safe and well-tolerated. Based on these data, the trial has achieved both goals within 28 weeks since the first dose.1

“These topline results from the Phase 2b VESPER-3 study reinforce the potential of PF’3944 as a monthly treatment with competitive efficacy,” Jim List, MD, PhD, chief internal medicine officer of Pfizer, said in a statement. “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 3.”1

VESPER-3 is an ongoing, 64-week, randomized, double-blind, placebo-controlled study designed to evaluate weekly (QW) titration phase to monthly (QM) dosing of PF’3944 compared to placebo. The trial includes a total of 4 separate titration and QM dose arms in addition to a placebo comparator. The primary endpoint is percent change from baseline in body weight at week 28, with secondary outcomes including percent change from baseline in body weight at week 64, change from baseline in absolute bodyweight in all protocol-specified weekly and monthly post-baseline measurements, and change from baseline in body mass at the same time, among other endpoints.1,2

Investigators enrolled patients with a body mass index (BMI) ≥30 kg (66.1 lbs)/m2 and ≤50 kg (110.2 lbs)/m2, or ≥27 kg (59.5 lbs)/m2 and <30 kg (66.1 lbs)/m2 with ≥1 of the following weight-related comorbidities:

• Hypertension: on blood pressure-lowering medication or with a systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg at screening
• Dyslipidemia: on lipid-lowering medication or with an LDL-C ≥160 mg/dL or triglycerides ≥150 mg/dL or HDL-C <40 mg/dL for men or <50 mg/dL for women at screening
• Stable body weight, defined as increases or decreases of ≤5 kg, within 3 months prior to screening.2

Patients were excluded if they had a diagnosis of diabetes or glycated hemoglobin A1c ≥6.5%, a history of pancreatitis, family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, or poorly controlled hypertension.2

Patients were randomly assigned across the 4 titration protocols: arm 1 (0.4 mg QW / 0.8 mg QW / 3.2 mg QM); arm 2 (0.8 mg QW / 3.2 mg QM); arm 3 (0.4 mg QW / 0.8 mg QW / 1.2 mg QW / 4.8 mg QM); arm 4 (0.6 mg QW / 1.2 mg QW / 4.8 mg QM); or arm 5 (placebo). A total of 54 participants were enrolled in each arm.1

By week 28, arm 1 achieved a 10% placebo-adjusted weight loss, and arm 3 achieved 12.3%; these are the low and medium monthly maintenance dosing regimens planned for future phase 3 investigation. PF’3944 also displayed a favorable safety and tolerability profile through week 28, consistent with the GLP-1 RA class. Observed treatment-emergent adverse events were primarily mild and moderate, with ≤1 instance of severe vomiting or nausea observed in each arm.1

Pfizer has also announced plans for an expansive obesity development program across its pipeline, with 10 phase 3 trials of PF’3944 planned for 2026. This includes the recently initiated phase 3 VESPER-4 pivotal study for patients with obesity or overweight without T2D, the planned phase 3 VESPER-5 study investigating once-weekly PF’3944 in patients with obesity or overweight with T2D, the planned phase 3 VESPER-6 study investigating once-monthly PF’3944 in obesity and overweight, and ≥7 additional planned studies targeting various comorbidities.1

“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,” List said.1

Pfizer has also announced that data from VESPER-3 will be presented on June 6, 2026, at the 86th Scientific Sessions of the American Diabetes Association.1

References

1. Pfizer, Inc. Pfizer’s Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial. BusinessWire. February 3, 2026. Accessed February 3, 2026. https://www.businesswire.com/news/home/20260202566685/en/Pfizers-Ultra-Long-Acting-Injectable-GLP-1-RA-Shows-Robust-and-Continued-Weight-Loss-with-Monthly-Dosing-in-Phase-2b-Trial

2. Metsera. A Phase 2b Study to Evaluate the Efficacy and Safety of Once-Monthly MET097 in Adults With Obesity or Overweight (VESPER-3). ClinicalTrials.gov Identifier: NCT06973720. Updated February 3, 2026. Accessed February 3, 2026. https://clinicaltrials.gov/study/NCT06973720