What Is MET-233i?

1. Where did MET-233i come from?

MET-233i was developed by Metsera, a New York biotech that went public in early 2025 with a portfolio of long-acting obesity peptides. Metsera’s lead drug was MET-097i, a GLP-1 receptor agonist designed for monthly dosing, and MET-233i was designed from the start to be its partner. In its merger filing, Metsera described MET-233i as an amylin analog “with enhanced solubility and miscibility with our other NuSH analog peptides,” meaning it was built to be mixed into the same syringe as its GLP-1 drug (Metsera merger proxy). NuSH stands for nutrient-stimulated hormone, the umbrella term the industry uses for gut and pancreatic hormones such as GLP-1, GIP and amylin.

Pfizer completed its purchase of Metsera on November 13, 2025, paying $65.60 per share in cash, an enterprise value of about $7.0 billion, plus a contingent value right of up to $20.65 per share tied to three clinical and regulatory milestones. At closing, Pfizer described MET-233i as a monthly amylin analog candidate in Phase 1, being studied alone and with MET-097i (Pfizer completion announcement). The molecule then took the Pfizer code PF-08653945. MET-097i became PF-08653944 and later received the generic name berobenatide.

2. How does MET-233i work?

MET-233i is a modified amylin peptide. Natural human amylin is a poor drug because it tends to clump into fibrils, sticky protein strands, both in the vial and after injection. Metsera says it designed MET-233i to lower that fibril-forming tendency, and then attached a lipid chain using its HALO platform so the peptide binds albumin, the most common protein in blood. Binding albumin shields the peptide from rapid clearance, which is the same basic strategy behind weekly semaglutide (Metsera merger proxy).

In Metsera’s laboratory tests, MET-233i activated the amylin 3 receptor about four times more potently than pramlintide and was characterized as a dual amylin and calcitonin receptor agonist, with no meaningful activity at other receptors tested. In rats, single doses lowered food intake and body weight in a dose-dependent way, and the two higher doses beat a synthesized version of cagrilintide on body weight at day 6. In pigs, its half-life was 114 hours, close to MET-097i’s 99 hours, when the two were injected together in one formulation (Metsera merger proxy). These are company-reported animal results, which do not predict human outcomes on their own.

Pfizer’s own pipeline lists PF-08653945 as an amylin analog “with dual amylin and calcitonin receptor activity” (Pfizer pipeline, November 3, 2026), and its June 2026 investor slides refer to it as a DACRA (Pfizer ADA presentation).

DACRA versus selective amylin agonists

Amylin receptors are made of the calcitonin receptor paired with a helper protein called a RAMP. Drugs that activate both the amylin receptors and the bare calcitonin receptor are called DACRAs; drugs that mostly hit the amylin receptors are called selective amylin receptor agonists, or SARAs. A 2026 review in Diabetes, Obesity and Metabolism places cagrilintide and petrelintide in the DACRA group and eloralintide and AstraZeneca’s AZD6234 in the SARA group. The authors note that it is still unclear whether this difference changes weight loss in practice, and that a possible bone benefit from calcitonin receptor activity “remains theoretical” (Alhazmi and le Roux, 2026).

3. What did the Phase 1 trial show?

Metsera reported topline results on June 9, 2025 from a randomized, double-blind, placebo-controlled Phase 1 trial in adults with overweight or obesity who did not have type 2 diabetes. It had two parts, all without dose titration (no gradual step-up) (Metsera Form 8-K):

• Single ascending dose (SAD): 40 participants received one dose of placebo or 0.15, 0.30, 0.60, 1.2 or 2.4 mg MET-233i, about six per active dose.
• Multiple ascending dose (MAD): 40 participants received five weekly doses of placebo or 0.15, 0.30, 0.60 or 1.2 mg, eight per group.

The 8.4% figure after five weeks is what drew attention: it is large for so short a trial. It is also based on eight people per group with no titration and no long follow-up, so it cannot be compared with the 68-week results of approved drugs. The 2026 DOM review lists MET-233i’s best figure as “~8.4% at 5 weeks” and its safety numbers as “not fully disclosed yet” (Alhazmi and le Roux, 2026).

Metsera also reported that the drug’s exposure after repeated doses matched that of MET-097i, which it said supports a monthly two-hormone combination (Metsera Form 8-K). Metsera’s press release added that the anticipated starting doses are 0.15 mg and 0.3 mg, with tolerability at those doses comparable to placebo, and that individual weight loss reached 10.2% (Metsera press release).

What the 19-day half-life means

Metsera measured half-life as the time from dosing to the point when the blood level falls to half of its peak. For comparison, semaglutide’s half-life is about a week. A half-life near three weeks is what makes a monthly schedule plausible, but it also means the drug takes a long time to leave the body after the last dose, which matters if side effects appear. The peptide half-life guide explains how levels build up and wash out over several half-lives.

Later Phase 1 parts

The Phase 1 study, registered as NCT07022977, grew to 144 participants and four parts. Part C tested 12 weekly doses followed by a 13th, potentially monthly, dose, and Part D tested 12 weekly doses followed by three monthly doses. The registry lists the study as completed on April 21, 2026. As of November 8, 2026, I found no public release of the Part C or Part D results.

4. What are the side effects of MET-233i?

The Phase 1 report gave detailed gastrointestinal counts (Metsera Form 8-K):

No severe events were recorded in either part. In the multiple-dose part, all GI events were mild and mostly confined to the first week, even though drug levels kept rising over the five weeks. That pattern, nausea at the start that fades with continued use, is typical of both amylin and GLP-1 drugs, and a 2026 review of long-acting amylin peptides describes nausea during initiation and dose increases as “commonplace” with this class (Peptides review, 2026).

Two cautions. First, a nausea rate of 100% at the top doses shows why the later trials use titration and lower starting doses. Second, a few dozen people over five weeks cannot reveal uncommon side effects. The Phase 2b trial is the first that can.

5. Why pair MET-233i with berobenatide?

Pfizer’s strategy treats berobenatide as the backbone and amylin as the add-on. The logic comes from Novo Nordisk’s CagriSema program. In REDEFINE 1, a 68-week Phase 3 trial in 3,417 adults with overweight or obesity and no diabetes, weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg produced a mean body-weight change of −20.4%, against −3.0% on placebo, under the treatment-policy estimand. Gastrointestinal events affected 79.6% of the combination group and 39.9% of the placebo group, mostly transient and mild to moderate (Garvey et al., NEJM 2025). The CagriSema guide covers that program in detail.

MET-233i and berobenatide aim for the same two-pathway effect with one injection a month instead of one a week. Pfizer’s June 2026 investor slides list the case for the combination: efficacy shown for each drug alone, “additive weight loss with combination established” in a Phase 1 single-ascending-dose study, pharmacokinetics that support monthly dosing, solubility that allows a fixed-dose combination in one syringe, and well-tolerated starting doses identified (Pfizer ADA presentation). CNBC reported in February 2026 that Pfizer said early data showed the two drugs together produced additive weight loss of 5% compared with placebo at day 8 (CNBC). That is a single-dose, one-week figure reported in the press, not peer-reviewed data, and it is not comparable with longer trials.

The deal terms show how central the combination is. Metsera’s September 2025 merger filing, written before the final price was agreed, defines the “Combination Product” as an injectable fixed-dose combination of MET-233i and MET-097i dosed on or around every 28 days, and ties contingent payments to its development (Metsera merger proxy).

6. What trials are running, and what is Pfizer’s status in November 2026?

Pfizer’s June 2026 berobenatide release described SOLIS-1 as a Phase 2b study of the amylin analog “as a monotherapy and in combination with berobenatide,” testing weekly and monthly maintenance dosing (Pfizer June 2026 release). Its June investor slides said PF’3945 monotherapy and combination data announcements were expected in the second half of 2026 (Pfizer ADA presentation).

The newest update came on Pfizer’s third-quarter earnings call on November 3, 2026. Chief Executive Albert Bourla said the Phase 2b study of the amylin combination program is fully enrolled. Chief Scientific Officer Chris Boshoff said SOLIS-1 efficacy results are expected in the second half of 2027, and that Pfizer would give an update on the Phase 1/2a combination study at the end of 2026, adding that the study “was designed for safety and PK, clinical pharmacology, not for efficacy.” Asked why that study enrolled 201 people rather than the roughly 400 an analyst said was originally planned, Boshoff said it had been adapted for additional pharmacokinetic studies and that nothing material had changed (Q3 2026 earnings call transcript). Pfizer’s pipeline document from the same day lists both PF-08653945 alone and berobenatide plus PF-08653945 in Phase 2 for chronic weight management (Pfizer pipeline).

As of November 8, 2026, the program is active, no Phase 3 trial of MET-233i is registered, and no regulatory filing has been made. I found no public release of 12-week or longer efficacy data for MET-233i alone or in combination.

7. How does MET-233i relate to GLP-1 therapy?

Most readers of this page are already on, or considering, a GLP-1 drug. Three points matter.

It is meant to be added to a GLP-1, not to replace one. Both MET-233i and berobenatide reduce appetite, but through different receptors. Amylin acts mainly in the brainstem’s area postrema and in the hypothalamus to end a meal, while GLP-1 drugs act on their own receptors in the brain and gut (Alhazmi and le Roux, 2026). The combination is expected to add weight loss, which is what REDEFINE 1 showed for cagrilintide plus semaglutide (Garvey et al., 2025). No trial has tested MET-233i with semaglutide or tirzepatide; the only GLP-1 partner studied is berobenatide.

The side effects overlap. Both classes slow gastric emptying and cause nausea, vomiting and constipation, especially early. In REDEFINE 1, GI events were twice as common on the combination as on placebo (Garvey et al., 2025). Stacking the two is why tolerability, not just weight loss, is the main question for SOLIS-1. Pfizer has said its goal is “category-leading weight loss and competitive tolerability” for the monthly combination (Pfizer ADA presentation).

Low blood sugar is a known amylin issue when insulin is involved. Pramlintide’s label carries a boxed warning that its use with insulin “increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes,” occurring within 3 hours of the injection (Symlin label). The MET-233i trials published so far enrolled people without diabetes, though the Phase 1/2a combination study included a cohort with type 2 diabetes (NCT06924320). How a monthly amylin analog behaves alongside insulin or sulfonylureas has not been reported.

Muscle and bone

GLP-1 weight loss includes some lean mass, a topic covered in GLP-1 and muscle loss. A 2025 review suggests that adding another hormone such as amylin to a GLP-1 drug “may lessen loss of lean mass,” but frames this as a hypothesis to be tested (review on preserving muscle mass). For DACRAs like MET-233i, a bone benefit through the calcitonin receptor has been proposed but not shown in trials (Alhazmi and le Roux, 2026). No body-composition data for MET-233i have been released.

8. How does MET-233i compare with other amylin drugs?

Result figures for the other drugs come from the 2026 DOM review table, which used data available through April 30, 2026 (Alhazmi and le Roux, 2026); stages are current as of November 2026 and come from each drug’s linked guide, or for AZD6234 from AstraZeneca’s pipeline. These are separate trials of very different lengths and designs, so the table shows the shape of the field rather than which drug is stronger. MET-233i’s distinguishing feature is the dosing interval: it is the only amylin analog in this list being developed for monthly injection, and the only one designed to share a syringe with a monthly GLP-1 drug.

For a personal log, an investigational drug is recorded like any other: product, date, dose and injection site, with the interval set to whatever the trial uses. How GLP-1 tracking works covers what to record. Until SOLIS-1 reports in 2027, MET-233i remains an early-stage candidate whose promise rests on small, short studies.

9. MET-233i FAQ

• Is MET-233i the same as PF-08653945?

  Yes. MET-233i was Metsera's code. After Pfizer bought Metsera in November 2025, the molecule became PF-08653945, often shortened to PF'3945 in Pfizer slides. Pfizer's June 2026 investor presentation also refers to it as a DACRA, short for dual amylin and calcitonin receptor agonist. It has no generic name or brand name yet.

• How much weight did people lose on MET-233i?

  In the Phase 1 trial reported in June 2025, five weekly doses of 1.2 mg produced a mean placebo-subtracted weight loss of 8.4% at day 36. A single 2.4 mg dose produced 5.3% placebo-subtracted loss at day 8. These are very short trials with about six to eight people per dose group, so they show that the drug is active rather than how much weight it would remove over a year.

• Is MET-233i a monthly injection?

  That is the goal. Metsera measured an observed half-life of about 19 days, and its follow-on Phase 1 parts tested 12 weekly doses followed by monthly doses. The Phase 2b SOLIS-1 trial tests weekly and monthly maintenance dosing. No monthly regimen has been proven in a long trial yet.

• Why combine MET-233i with berobenatide?

  Amylin analogs and GLP-1 drugs reduce appetite through partly different pathways, and the combination of cagrilintide with semaglutide produced more weight loss than either drug alone in Novo Nordisk's trials. Pfizer is betting that a once-monthly amylin plus GLP-1 combination could match that benefit with one injection a month. Metsera reported that the two molecules have matching pharmacokinetics, which makes a single fixed-dose injection possible.

• What are the side effects of MET-233i?

  In Phase 1, gastrointestinal effects were the most common and rose with dose. After a single 2.4 mg dose, all six participants had nausea and five of six vomited, all mild. In the five-week multiple-dose part, side effects were all mild and mostly in the first week, and none of the three dropouts was attributed to side effects. Larger trials will give better numbers.

• When will MET-233i be available?

  There is no filing and no approval date. As of November 8, 2026, Pfizer lists PF-08653945 alone and with berobenatide in Phase 2. SOLIS-1 has an estimated primary completion in August 2027, and Pfizer expects efficacy results in the second half of 2027. Phase 3 would come after that, so any approval is years away.

• Can I buy MET-233i online?

  Not legitimately. MET-233i is only available inside Pfizer's clinical trials. Products sold online under this name are not the investigational drug, have not been tested in these trials, and cannot be verified.

10. Sources