What Is Berobenatide (MET-097i)?

1. How does berobenatide work?

The receptor pharmacology is that of semaglutide: a single agonist at the GLP-1 receptor, producing glucose-dependent insulin release, slower gastric emptying, and reduced appetite. Unlike the dual and triple agonists elsewhere in this library, berobenatide does not add GIP or glucagon activity. Its distinguishing feature is duration. Semaglutide’s half-life of about a week comes from binding albumin; berobenatide is built on Metsera’s HALO platform, described in the company’s own SEC filing as “a novel peptide stabilization and lipidation platform technology that enables peptides to bind simultaneously to albumin and to a drug target, designed to facilitate a half-life approaching that of albumin.”

Albumin itself persists in circulation for roughly three weeks, which is the basis for monthly dosing. Metsera’s 2024 annual report (Form 10-K) discloses a measured figure: single-ascending-dose data showed “dose-proportional PK with an approximately 380-hour half-life with modest variability,” roughly 15 to 16 days.

The practical implication is dosing frequency. Every approved GLP-1 injection is weekly or daily. A monthly injection would change adherence, the missed-dose problem, and the size of the dose per injection, which is why the milligram numbers on this page, 0.4 to 2.4 mg, are not comparable with any other GLP-1 drug’s. In VESPER-3, the monthly maintenance dose is roughly four times the weekly dose that preceded it, reflecting the longer interval rather than a stronger drug.

2. How much weight do people lose on berobenatide?

VESPER-1, the Phase 2b weekly-dosing trial, randomized 239 adults with obesity or overweight and no diabetes to placebo or four doses (roughly 54 per arm) for 28 weeks, without dose titration. The trial population had an average BMI of about 36 and was roughly two-thirds female. Some individual participants lost as much as 26.5% of body weight.

VESPER-3, NCT06973720, is the trial that tests the monthly idea: 268 adults received 12 weekly doses (with or without titration, depending on arm), then switched to monthly maintenance dosed at roughly four times the weekly amount, with five arms including placebo. The two monthly regimens (arms described by Pfizer as the 3.2 mg and 4.8 mg maintenance doses) produced 10.0% and 12.3% placebo-adjusted weight loss under the efficacy estimand, the analysis that counts people only while they stay on the drug, and 8.4% and 10.5% under the treatment-policy estimand, the stricter analysis that counts everyone who was randomised whether or not they stopped.

Both were significant against placebo. The trial started April 7, 2025 and its primary endpoint at week 28 was followed by a longer observation through week 64.

For scale, semaglutide 2.4 mg produced 14.9% at 68 weeks in STEP 1 and tirzepatide 15 mg 20.9% at 72 weeks in SURMOUNT-1, both raw rather than placebo-adjusted and in longer trials. Berobenatide’s 28-week numbers are in semaglutide’s range; the 64- and 72-week Phase 3 endpoints will show where it lands.

3. What are the side effects of berobenatide?

Gastrointestinal, and the discontinuation numbers are the lowest in this library.

Pfizer attributes the tolerability to the pharmacokinetics: a very long-acting drug rises to its level slowly, which is the same reason dose escalation reduces nausea with weekly drugs. Whether the profile holds over 64 to 72 weeks and in thousands of people is what Phase 3 is for.

Metsera’s own September 2025 disclosure of the VESPER-1 data credited the CMO, Dr. Steve Marso, with describing the results as “dual-agonist-like weight loss of 14.1% at 28 weeks, with only 2.9% study discontinuation,” and UNC’s Dr. John Buse called MET-097i “the first NuSH analog in late-stage clinical development that I am aware of that is on track to meet” the efficacy and tolerability bar set by tirzepatide. No peer-reviewed publication exists yet; all figures come from Pfizer’s and Metsera’s releases, an SEC exhibit, and 2026 conference presentations.

4. What is the VESPER Phase 3 program?

Pfizer moved berobenatide into Phase 3 in December 2025, when VESPER-4 started, and has since registered a roster of trials, each testing a different population or regimen on the registry:

VESPER-4 started December 19, 2025 and VESPER-5 February 24, 2026, with 64-week primary endpoints; both are now active and not recruiting, meaning enrollment is complete. VESPER-6 started June 10, 2026, with primary completion estimated for May 2028. VESPER-OSA 1, VESPER-SWITCH, VESPER-JW and the weekly China trial began recruiting between September and early October 2026; VESPER-JM and the monthly China trial were listed as not yet recruiting in mid-October 2026. Sizes for trials still enrolling are registry estimates. Pfizer’s June 2026 release says 10 Phase 3 studies are planned or under way, including knee osteoarthritis, which had no registered trial as of October 15, 2026. SOLIS-1, a Phase 2b trial rather than Phase 3, shows Pfizer also testing berobenatide alongside a second investigational molecule, the amylin analog PF-08653945, which Metsera developed as MET-233i. No regulatory filing has been made.

5. Why did Pfizer pay $7 billion?

Pfizer completed its acquisition of Metsera on November 13, 2025 at $65.60 per share in cash, an enterprise value of about $7.0 billion, plus a contingent value right worth up to $20.65 per share tied to three specified clinical and regulatory milestones. Pfizer had no obesity drug after discontinuing danuglipron, its oral GLP-1, in April 2025; Metsera’s portfolio gave it one about to enter Phase 3. After the deal, Pfizer renamed the molecule PF-08653944; the generic name berobenatide followed. Metsera’s earlier-stage assets, not part of the VESPER Phase 3 program, included a monthly amylin-analog combination (MET-233/097), a GIP-receptor combination, and an oral formulation (MET-097o), all Phase 1 or Phase 1/2a at the time of the deal.

Pfizer’s February and June 2026 releases describe plans for 10 Phase 3 studies of berobenatide in 2026, part of a broader program of more than 20 obesity trials. Trade press coverage of the February 2026 data quoted Leerink Partners analyst David Risinger calling the early results “slightly inferior” to tirzepatide’s roughly 13% placebo-adjusted weight loss at 28 weeks in cross-trial comparison, a comparison with the usual limitations of comparing separate trials.

6. How does berobenatide compare with the approved drugs?

MariTide is the other monthly candidate, built on an antibody rather than an engineered peptide. For a log, an investigational drug is entered like any other: product, date, milligrams, and site, with the interval set to 4 weeks for monthly dosing. How GLP-1 tracking works covers what to record.

Pfizer’s own framing, in trade-press coverage of the February 2026 data, put a rough date on the earliest possible outcome: Chief Scientific Officer Chris Boshoff described Pfizer as “targeting potential approvals starting in 2028,” which depends on Phase 3 success. That timeline is consistent with the registry’s estimated primary completions for VESPER-4 (September 2027), VESPER-5 (October 2027) and VESPER-6 (May 2028). Until then, berobenatide, MET-097i, and PF-08653944 all describe the same investigational molecule available only to people enrolled in one of Pfizer’s trials.

7. Berobenatide FAQ

• How much weight do people lose on berobenatide?

  In VESPER-1 at 28 weeks, 8.1% to 14.1% placebo-adjusted across four weekly doses, with 14.1% at 1.2 mg. In a 32-week extension, participants who had been on placebo through week 28 then escalated to 2.4 mg weekly and reached 15.9% total (non-placebo-adjusted) weight loss by week 60, with weight still falling; this figure reflects 32 weeks of active treatment, not 60 weeks of continuous dosing. In VESPER-3, switching to monthly injections after 12 weekly doses produced 10.0% and 12.3% placebo-adjusted loss at 28 weeks.

• Is berobenatide a monthly injection?

  That is the design goal. The molecule is engineered to circulate for weeks, and VESPER-3 tested 12 weekly doses followed by monthly maintenance. The Phase 3 trial VESPER-6 tests once-monthly dosing, described by Pfizer as monthly maintenance, in 954 adults over 72 weeks; VESPER-SWITCH tests moving people already on weekly semaglutide or tirzepatide to monthly berobenatide. Every approved GLP-1 injection is weekly or daily.

• What are the side effects of berobenatide?

  Gastrointestinal, at rates Pfizer describes as low for the class. In VESPER-1, the excess risk of nausea over placebo ran from 4% to 23% depending on dose, only 2 of 239 participants stopped for adverse events, and total discontinuation was 2.9%. In VESPER-3, across the two monthly regimens planned for Phase 3, five participants stopped for adverse events during the weekly phase and five during the monthly phase, against none on placebo, with severe nausea or vomiting at most once per dose group.

• What is the difference between MET-097i, PF-08653944, and berobenatide?

  Three names for one molecule. MET-097i was Metsera's code. PF-08653944 is Pfizer's code after the acquisition. Berobenatide is the generic name. Pfizer's own materials also use the shorthand PF'3944.

• When will berobenatide be approved?

  No filing exists. Phase 3 trials started in December 2025; VESPER-6 lists primary completion in May 2028, so a filing would follow those readouts and approval would come later. No peer-reviewed publication of the Phase 2 data exists yet; the numbers come from Pfizer's and Metsera's releases, an SEC exhibit, and conference presentations.

• How many Phase 3 trials is Pfizer running for berobenatide?

  Pfizer says it plans 10 Phase 3 studies of berobenatide in 2026, including knee osteoarthritis and obstructive sleep apnea, within a program of more than 20 obesity trials. As of October 15, 2026, nine are registered as Phase 3: VESPER-4 (3,578 adults, weekly, no diabetes), VESPER-5 (1,078 adults, weekly, with type 2 diabetes), VESPER-6 (954 adults, monthly maintenance), VESPER-OSA 1 (258 adults with sleep apnea on PAP, monthly), VESPER-SWITCH (660 adults switching from weekly semaglutide or tirzepatide to monthly), VESPER-JM and VESPER-JW (197 and 180 adults in Japan, monthly and weekly), and two trials in Chinese adults (300 weekly, 432 monthly). SOLIS-1, combining PF-08653944 with Pfizer's ultra-long-acting amylin analog PF-08653945 (formerly MET-233i) in 940 adults, is registered as Phase 2b, not Phase 3.

8. Sources