Pfizer's Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial
- VESPER-3 reinforces confidence in monthly dosing of PF-08653944 (MET-097i), including the potential for higher dosing regimens in Phase 3
- Study met primary endpoint of statistically significant weight reduction at 28 weeks with a competitive tolerability profile
- Weight loss continued after pre-planned switch from weekly to monthly dosing, with no plateau observed at 28 weeks
- 10 Phase 3 trials with PF'3944 expected to advance in 2026; expansive clinical development program underway with 20+ planned and ongoing studies across diverse obesity pipeline
Pfizer Inc. (NYSE:PFE) today announced positive topline results from the Phase 2b VESPER-3 study investigating monthly maintenance dosing of its fully-biased, ultra-long-acting, injectable GLP-1 receptor agonist (RA) PF'3944 (MET-097i) in adults with obesity or overweight without type 2 diabetes. The study had two objectives:
(1) to demonstrate PF'3944 could achieve continued weight loss when switching from weekly to monthly subcutaneous injections and maintain its efficacy while reducing the dosing frequency four-fold; and
(2) to demonstrate PF'3944 could switch to a four-fold equivalent monthly dose while maintaining a well-tolerated and favorable safety profile.
The study demonstrated statistically significant weight reduction with up to 12.3% mean placebo-adjusted weight loss at week 28 (efficacy estimand*). The study included up to two titration steps and weekly dosing with PF'3944 until week 12, followed by monthly dosing to week 28. The primary endpoint of weight reduction from randomization to week 28 was superior to placebo in all four dose regimens tested (P < 0.001). The detailed results from VESPER-3 will be presented on June 6, 2026, at the 86th Scientific Sessions of the American Diabetes Association.®
VESPER-3 is an ongoing 64-week, randomized, double-blind, placebo-controlled study in participants with obesity or overweight without type 2 diabetes. The study is designed to evaluate weekly (QW) titration phase to monthly (QM) dosing of PF'3944 in four different titration and QM dose arms, compared to placebo (five arms, ~n=54 per arm). Participants were randomized across four 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). Interim tolerability results were previously reported after 12 weeks of weekly dosing by Metsera; these topline results reflect efficacy and tolerability data from an additional 16 weeks with monthly dosing.
At week 28, 10% and 12.3% placebo-adjusted weight loss* was achieved in Arms 1 and 3 respectively, which are the low and medium monthly maintenance dosing regimens planned for inclusion in Phase 3. These data show robust and continuous weight loss after switching to monthly dosing, with no plateau observed at week 28, suggesting continued weight loss is expected as the study continues through week 64.
PF'3944 also maintained a well-tolerated and favorable safety profile through week 28 that is consistent with the GLP-1 RA class. Observed gastrointestinal treatment-emergent adverse events (TEAEs) were predominantly mild or moderate with no more than one instance of severe nausea or vomiting observed in any dose group, and no instances of severe diarrhea. Across Arms 1 and 3, five total participants discontinued from treatment due to adverse events (AEs) in the weekly phase and five total participants discontinued from treatment due to AEs in the monthly phase. There were zero discontinuations from treatment due to AEs in the placebo group.
"These topline results from the Phase 2b 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. "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. 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."
Following its recent acquisition of Metsera and exclusive global collaboration and license agreement with YaoPharma, Pfizer now has a diverse pipeline of clinical stage injectable and oral obesity candidates targeting GLP-1 receptor as well as glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists and antagonists, and amylin analogs. Pfizer is planning an expansive obesity development program across its robust pipeline, with plans to advance 20+ trials in 2026. This includes 10 Phase 3 trials of PF'3944, including the recently initiated Phase 3 VESPER-4 pivotal study investigating once-weekly PF'3944 in people with obesity or overweight and without type 2 diabetes; the planned Phase 3 VESPER-5 study investigating once-weekly PF'3944 in people with obesity or overweight with type 2 diabetes; the planned Phase 3 VESPER-6 study with once-monthly PF'3944 in obesity or overweight; and at least seven additional planned Phase 3 studies of PF'3944 designed to target comorbidities and increase patient optionality and access.
About PF-08653944 (PF'3944; previously called MET-097i)
PF'3944 is an ultra-long-acting fully biased GLP-1 receptor agonist (RA). It is being developed as a single agent weekly and as a monthly therapy, and in combination with various peptides including an amylin analog PF-08653945 (PF'3945; MET-233i) and a GIPR agonist PF-08654696 (MET-034i).
About Obesity
Obesity is a growing global epidemic. In 2015, it was estimated that approximately 1.9 billion people were living with obesity or considered overweight, and this number is expected to grow to more than 2.9 billion by 2030.i Obesity is a complex metabolic disease, often defined in adults as having a body mass index (BMI) greater than or equal to 30.ii It is associated with more than 200 health conditions,iii contributing to significant chronic disease burden, shortened lifespans, and growing healthcare costs. Despite recent advances in care, for many patients, current therapies are not sufficient—whether due to limited efficacy, tolerability issues that impact adherence, associated muscle mass and strength loss (sarcopenia), co-morbidities that weight loss alone doesn't address, or barriers to access and affordability. New waves of innovation that better meet the diverse needs of patients are critical to effectively address this epidemic.
About Pfizer: Breakthroughs That Change Patients' Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
Disclosure Notice
The information contained in this release is as of February 3, 2026. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about PF-08653944 (PF'3944; previously called MET-097i), an investigational fully-biased, ultra-long-acting, injectable GLP-1 receptor agonist, and results from the Phase 2b VESPER-3 trial and expectations for continued weight loss as the study continues, potential product profile, Pfizer's investigational obesity portfolio, and anticipated clinical trial starts and clinical development plans, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data, including the risk that analysis of longer term data does not match our expectations based on the data disclosed in this release; risks associated with initial, preliminary or interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities, including the population regulatory authorities deem relevant for regulatory decisions; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; whether and when drug applications may be filed in any jurisdictions for PF'3944 or any other product candidates for any potential indications; whether and when any such applications may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether PF'3944 or any such other product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of PF'3944 or any such other product candidates; whether our collaboration and license agreement with YaoPharma will be successful; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws or regulations; uncertainties regarding the impact of COVID-19 on Pfizer's business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
*Least squares mean difference from placebo calculated using a mixed model for repeated measures excluding protocol-defined intercurrent events (i.e., efficacy adherence to study dataset). For the treatment policy estimand, using all available weight measurements regardless of treatment adherence, placebo-adjusted weight loss was 8.4% for Arm 1 and 10.5% for Arm 3.
i World Obesity Atlas 2025
ii World Health Organization. Obesity and Overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
iii American Medical Association. Obesity. https://www.ama-assn.org/topics/obesity.
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