MET-233i: The Once-Monthly Amylin Injection Built to Pair With a Monthly GLP-1 (July 31, 2026)
Table of Contents
Why a monthly amylin drug matters
Amylin has become one of the most sought-after targets in obesity medicine. It is a hormone the pancreas releases alongside insulin, and it curbs appetite, slows how fast the stomach empties, and - importantly - tends to strip away fat while sparing muscle, the 'quality weight loss' the field is chasing. The snag is that the leading amylin candidates, from cagrilintide to petrelintide to Eli Lilly's eloralintide, are injections given every week. MET-233i's pitch is to keep amylin's biology but stretch the dosing interval out to once a month, which for many people is the difference between a drug they stick with and one they quietly abandon.
What Metsera has shown so far
In a Phase 1 trial, MET-233i produced dose-dependent, placebo-subtracted weight loss of up to 8.4% at Day 36 after just five weekly doses, with some individuals losing as much as 10.2%. The study was a randomized, double-blind, placebo-controlled trial in 80 adults with overweight or obesity and without type 2 diabetes, testing single doses from 0.15 mg up to 2.4 mg and multiple doses up to 1.2 mg weekly for five weeks - notably without any titration. The drug was generally well tolerated with no safety signals, and the gastrointestinal side effects that did occur were mostly mild and clustered in the first week, hinting that the body adapts quickly.
The half-life is the headline
The single most important number in the MET-233i story is its half-life: about 19 days, which Metsera has called the most durable pharmacokinetic profile of any known amylin analog. That durability is what makes once-monthly dosing plausible, and it is unusual for a peptide - most amylin agents clear fast enough to require weekly injections. A long, flat exposure curve can also smooth out the peaks that drive nausea, which may help explain why the early tolerability looked clean. The trade-off is that a drug that lingers for weeks leaves less room to dial the dose down quickly if a patient does not tolerate it, something longer trials will need to probe.
The combination play: MET-233/097
MET-233i was not designed to stand alone. Metsera engineered it to match the roughly 19-day half-life and the multi-dose exposure of its ultra-long-acting GLP-1 receptor agonist, MET-097i, so the two can be given together on the same monthly schedule. That pairing, referred to as MET-233/097, is aimed at being a first-in-category once-monthly GLP-1-plus-amylin combination - essentially an infrequent-dosing answer to injectable combinations like CagriSema and MariTide. A 12-week co-administration study was launched to test whether the two peptides add up to more than either alone, with early data expected around the turn of 2026.
Now a Pfizer asset
MET-233i changed hands in late 2025. Pfizer completed its acquisition of Metsera on November 13, 2025, folding the amylin candidate and its GLP-1 partner MET-097i into Pfizer's obesity pipeline. For a company that had stumbled with an earlier oral GLP-1 program, the deal rebuilt Pfizer's obesity story around monthly injectables and combination therapy, and it put MET-233i at the center of that strategy rather than on the periphery of a small biotech. That backing matters for a Phase 1 asset: the resources to run large, long combination trials are exactly what the program now needs.
Where it sits versus the field
On the amylin leaderboard, MET-233i is early - it has Phase 1 monotherapy data where cagrilintide and petrelintide have Phase 2 and beyond, and where eloralintide is further along in Lilly's hands. What sets MET-233i apart is not raw weight loss, which at five weeks is not directly comparable to longer trials, but its dosing ambition. If a monthly amylin shot can match the weekly agents on efficacy and tolerability over a full course of treatment, convenience alone could make it competitive - and the monthly GLP-1-plus-amylin combination could be a genuinely differentiated product rather than a me-too.
Safety and status note
MET-233i is investigational and not approved anywhere. The human data so far come from a single short Phase 1 study, so its longer-term efficacy, durability, lean-mass benefit and safety - and those of the MET-233/097 combination - remain unproven. It is not available outside clinical trials and is not a compounding-eligible peptide; any 'MET-233i' sold by a vendor is unverified. This article is educational and is not medical advice.
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Citations
- [1] Metsera - Positive Phase 1 Data of First-in-Class Once-Monthly Amylin Candidate MET-233i (Jun 9, 2025) Source
- [2] BioSpace - Metsera Announces Positive Phase 1 Data of Once-Monthly Amylin Candidate MET-233i Source
- [3] Metsera - Positive Phase 2b Results for Ultra-Long-Acting GLP-1 RA MET-097i Source
- [4] Pfizer - Pfizer Completes Acquisition of Metsera (Nov 13, 2025) Source
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