MET-097i
Medium EvidenceAn ultra-long-acting GLP-1 receptor agonist designed for both once-weekly and once-monthly subcutaneous dosing, delivering double-digit weight loss with class-leading gastrointestinal tolerability in mid-stage trials.
What It Is
MET-097i is an investigational ultra-long-acting GLP-1 receptor agonist originally developed by Metsera and now owned by Pfizer, which completed its acquisition of Metsera in November 2025 (enterprise value ~$7 billion plus a contingent value right of up to $20.65 per share, after a high-profile bidding war with Novo Nordisk). MET-097i is engineered with a fatty-acid-based half-life-extension technology that gives it an exceptionally long duration of action, enabling not only conventional once-weekly subcutaneous dosing but also a once-monthly maintenance regimen — a dosing interval no approved incretin therapy currently offers. The drug is being positioned as a potential best-in-class injectable GLP-1 differentiated on two fronts: convenience (monthly maintenance injections) and tolerability. In an earlier Phase 2b study, MET-097i produced approximately 14.1% mean weight loss with weekly dosing. In the VESPER-3 Phase 2b trial of once-monthly maintenance dosing, the compound met its primary endpoint with statistically significant placebo-adjusted weight reductions of 10% and 12.3% at week 28 on the low and medium monthly maintenance regimens planned for Phase 3, and importantly showed continued weight loss with no plateau after participants switched from weekly to monthly dosing. Tolerability was a defining feature: the trial reported a placebo-like frequency of diarrhea and a relatively low risk difference versus placebo for nausea (~13%) and vomiting (~11%), which Pfizer characterized as potentially class-leading. Pfizer has said roughly 10 Phase 3 trials with MET-097i (referred to internally as PF-'3944) are expected to advance in 2026, and the molecule anchors a broader next-generation obesity portfolio acquired from Metsera that also includes the amylin analog MET-233i and planned GLP-1/amylin combination programs. MET-097i is investigational and not approved in any jurisdiction.
Regulatory Status
VESPER-3 Phase 2b once-monthly maintenance study met its primary weight-loss endpoint at 28 weeks (reported February 2026). Pfizer expects ~10 Phase 3 trials with MET-097i (PF-'3944) to advance in 2026. Acquired by Pfizer via the completed Metsera acquisition (November 2025). Not approved in any jurisdiction.
Effective: June 2026
View FDA SourceWhy Researchers Study It
MET-097i is closely watched because it pairs double-digit weight loss with a once-monthly maintenance dosing option that no approved incretin therapy currently offers, plus a tolerability profile that Pfizer describes as potentially class-leading. It is studied as a potential best-in-class injectable GLP-1 differentiated on convenience and tolerability rather than peak efficacy alone, and as the anchor of Pfizer's next-generation obesity portfolio (including the amylin analog MET-233i and planned GLP-1/amylin combinations) following the company's ~$7 billion acquisition of Metsera.
Proposed Mechanisms
- Agonizes the GLP-1 receptor to reduce appetite, enhance satiety, and improve glycemic control
- Fatty-acid half-life-extension chemistry produces an ultra-long duration of action
- Ultra-long half-life enables both once-weekly and once-monthly subcutaneous dosing
- Engineered for class-leading gastrointestinal tolerability (low nausea and vomiting vs placebo)
- Designed to serve as a backbone for combination with an amylin analog (MET-233i)
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Human (Phase 2b, weekly dosing) | Adults with obesity or overweight | Approximately 14.1% mean weight loss with once-weekly dosing; described by the company as competitive efficacy with class-leading tolerability | Source |
| Human (Phase 2b, VESPER-3, monthly maintenance) | Adults with obesity transitioning from weekly to once-monthly maintenance dosing | Met primary endpoint at week 28: placebo-adjusted weight loss of 10% (low) and 12.3% (medium) on the monthly maintenance regimens planned for Phase 3; continued weight loss with no plateau after switching to monthly; nausea risk difference ~13% and vomiting ~11% vs placebo, diarrhea placebo-like | Source |
| Corporate / development | Pfizer acquisition of Metsera and Phase 3 planning | Pfizer completed the Metsera acquisition in November 2025 (~$7B enterprise value plus CVR up to $20.65/share); ~10 Phase 3 trials with MET-097i (PF-'3944) expected to advance in 2026 | Source |
Commonly Discussed Benefits
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Safety & Cautions
- Investigational; not approved in any jurisdiction
- Only Phase 2b efficacy and tolerability data reported to date; Phase 3 outcomes and long-term safety unknown
- Full VESPER-3 data not yet peer-reviewed/published
- Available only through clinical trial enrollment
- Not FDA-approved; not a compounding-eligible peptide
- GLP-1-class effects (nausea, vomiting, GI symptoms) can still occur despite the favorable tolerability profile reported
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Citations
- [1] Pfizer's Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial (Feb 2026) PubMed
- [2] Pfizer Completes Acquisition of Metsera (Nov 2025) PubMed
- [3] Pfizer's obesity bet shows 14.1% weight loss in Phase IIb trial — Clinical Trials Arena PubMed
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MET-233i
Medium EvidenceMET-233i is a first-in-class, once-monthly ultra-long-acting amylin analog for obesity, originally developed by Metsera and now a Pfizer asset. In its Phase 1 trial it produced up to 8.4% placebo-subtracted weight loss after five weekly doses and showed a roughly 19-day half-life - the most durable of any reported amylin analog - supporting once-monthly subcutaneous dosing. It is engineered to be combined with Metsera's monthly GLP-1 agonist MET-097i in a single once-monthly injection.