MET-233i

What It Is

MET-233i is an injectable, ultra-long-acting analog of amylin - a pancreatic hormone co-secreted with insulin that promotes satiety, slows gastric emptying and tends to preserve lean mass during weight loss - being developed for obesity. It was created by Metsera using the company's peptide half-life-extension platform and became part of Pfizer's obesity pipeline when Pfizer completed its acquisition of Metsera on November 13, 2025. Amylin has emerged as one of the most clinically validated non-GLP-1 targets in obesity medicine, and most amylin front-runners - cagrilintide, petrelintide and Eli Lilly's selective agonist eloralintide - are peptides given by weekly subcutaneous injection. MET-233i's distinguishing feature is durability: in its Phase 1 study it showed an observed half-life of about 19 days, which Metsera described as the most durable pharmacokinetic profile of any known amylin analog and enough to support once-monthly dosing with simplified or no titration. The Phase 1 trial was a randomized, double-blind, placebo-controlled study in 80 participants with overweight or obesity and without type 2 diabetes, evaluating single subcutaneous doses from 0.15 mg to 2.4 mg and multiple doses from 0.15 mg to 1.2 mg given once weekly for five weeks without titration. Weight loss was dose-dependent, reaching a placebo-subtracted mean of 8.4% at Day 36 after five weekly 1.2 mg doses, with individual responses as high as 10.2%, and the drug was generally well tolerated with no safety signals; most gastrointestinal adverse events were mild, dose-dependent and concentrated in the first week, suggesting rapid tolerance development. The strategic point of MET-233i is combinability. It shares a roughly 19-day half-life with Metsera's ultra-long-acting GLP-1 receptor agonist MET-097i, and its multi-dose exposure profile matched that of MET-097i, supporting a first-in-category once-monthly 'multi-NuSH' (nutrient-stimulated hormone) combination that would pair GLP-1 and amylin biology in a single monthly injection - an infrequent-dosing analog of the injectable GLP-1-plus-amylin combinations CagriSema and MariTide. A 12-week co-administration trial of MET-233i with MET-097i (referred to as MET-233/097) was initiated to test that thesis, with topline data expected around year-end 2025 or early 2026. MET-233i reflects two of 2026's dominant obesity-drug themes: the 'amylin renaissance,' in which lean-mass-sparing amylin mechanisms are pursued as the next pillar beyond GLP-1, and the push toward less frequent, once-monthly dosing to improve adherence.

Regulatory Status

Why Researchers Study It

MET-233i is watched because it tests whether amylin - one of the most validated non-GLP-1 obesity mechanisms, and one prized for sparing lean mass - can be delivered as a durable, once-monthly injection rather than a weekly one. Its roughly 19-day half-life is the longest reported for any amylin analog, and its early weight loss and clean first-week-limited tolerability profile position it as a potential best-in-class amylin backbone. It is also a purpose-built combination partner: engineered to match the half-life and exposure of the monthly GLP-1 agonist MET-097i, it could enable a first-in-category once-monthly GLP-1-plus-amylin injection (MET-233/097), the infrequent-dosing analog of CagriSema and MariTide. As a centerpiece of Pfizer's post-acquisition obesity strategy, it is closely followed by clinicians and investors tracking the 2026 'amylin renaissance' and the move toward monthly dosing.

Proposed Mechanisms

• Agonizes the amylin receptor (calcitonin receptor paired with RAMP proteins) to promote satiety, slow gastric emptying and reduce food intake
• Ultra-long-acting peptide engineering gives an observed half-life of about 19 days - the most durable reported for an amylin analog - supporting once-monthly subcutaneous dosing with simplified or no titration
• Aims to preserve lean mass during weight loss, a hallmark attributed to amylin-pathway signaling
• Matched half-life and exposure with the monthly GLP-1 agonist MET-097i, enabling a co-formulated once-monthly GLP-1-plus-amylin 'multi-NuSH' combination (MET-233/097)
• Delivered as a subcutaneous injection rather than an oral small molecule

Evidence Snapshot

Commonly Discussed Benefits

Safety & Cautions

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Citations

1. [1] Metsera - Positive Phase 1 Data of First-in-Class Once-Monthly Amylin Candidate MET-233i (Jun 9, 2025) PubMed
2. [2] BioSpace - Metsera Announces Positive Phase 1 Data of First-in-Class Once-Monthly Amylin Candidate MET-233i PubMed
3. [3] Metsera - Positive Phase 2b Results for Ultra-Long-Acting GLP-1 RA MET-097i (combination partner context) PubMed
4. [4] Pfizer - Pfizer Completes Acquisition of Metsera (Nov 13, 2025) PubMed

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