Berobenatide (MET-097i, now Pfizer’s PF-08653944) is an investigational GLP-1 receptor agonist built to last long enough in the body for once-monthly injection. In its phase 2b trial, the highest weekly dose beat placebo by 14.1 percentage points of body weight after 28 weeks, and only 2 of 239 participants stopped because of side effects. It is in phase 3 and is not approved anywhere.
The developer, Metsera, was bought by Pfizer in November 2025. As of November 7, 2026, ClinicalTrials.gov lists 12 phase 3 trials of the drug. Pfizer has said it is “targeting potential approvals starting in 2028” (MedCity News, February 2026). No body-composition (fat vs lean mass) data have been published, and none of the registered trials lists lean mass as an outcome.
This page summarizes what the trial registrations, company filings and conference reports say. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | GLP-1 receptor agonist (single receptor), lipidated peptide with ultra-long half-life |
| Codes and names | MET-097i, MET097 (Metsera); PF-08653944, PF’3944 (Pfizer); berobenatide (generic name) |
| Developer | Pfizer, via its acquisition of Metsera (completed November 13, 2025) |
| Route | Subcutaneous injection, weekly or monthly |
| Doses studied | 0.4–1.2 mg weekly (phase 2b), 2.4 mg weekly (extension); monthly maintenance doses of 3.2–4.8 mg (phase 2b) and 9.6 mg (phase 3) |
| Half-life | About 380 hours (roughly 16 days) in a single-dose study |
| Status (November 7, 2026) | Phase 3 (VESPER program); no regulatory filing; not approved |
| WADA status | Not named on the 2026 List; unapproved, so it falls under S0 (non-approved substances) |
What it is
Berobenatide acts at the same receptor as semaglutide: the GLP-1 receptor, which reduces appetite, slows stomach emptying and raises insulin when blood sugar is high. It does not add GIP activity like tirzepatide or glucagon activity like retatrutide.
Its distinguishing feature is duration. Metsera built it on its HALO (“Half-life Augmentation by Lipid Optimization”) platform. In Metsera’s description, HALO lets a peptide bind albumin, the main blood protein, while also binding its drug target. That aims for a half-life closer to albumin’s own lifespan (Metsera 2024 Form 10-K). Metsera also described it as “fully biased,” meaning it was designed to favor one signaling pathway inside the cell over others (Metsera VESPER-1 release, SEC Exhibit 99.1). Whether that bias makes a clinical difference has not been tested directly.
Pfizer completed the purchase of Metsera on November 13, 2025, for $65.60 per share in cash (about $7.0 billion in enterprise value), plus a contingent value right of up to $20.65 per share tied to three milestones (Pfizer release via BioSpace).
How it compares with related drugs
| Drug | Receptors | Dosing interval | Status (November 2026) | Library page |
|---|---|---|---|---|
| Semaglutide | GLP-1 | Weekly | Approved | Semaglutide |
| Berobenatide | GLP-1 | Weekly or monthly | Phase 3 | This page |
| Tirzepatide | GIP and GLP-1 | Weekly | Approved | Tirzepatide |
| MariTide | GLP-1 agonist, GIP antagonist (antibody-peptide) | Monthly or less often | Phase 3 | MariTide |
| Orforglipron | GLP-1 (oral small molecule) | Daily pill | See page | Orforglipron |
Pharmacokinetics
Metsera’s annual report described a single-ascending-dose trial that showed “dose-proportional PK with an approximately 380-hour half-life with modest variability.” The company said this was about two times longer than semaglutide’s and three times longer than tirzepatide’s (Metsera 2024 Form 10-K). This half-life comes from a company filing; we did not find a peer-reviewed pharmacokinetic paper.
Two consequences follow:
- Milligram doses are not comparable with other GLP-1 drugs. Weekly doses in phase 2b were 0.4–1.2 mg, far lower than semaglutide’s 2.4 mg.
- Monthly doses are larger. In Pfizer’s plans, a 9.6 mg monthly dose is treated as equivalent to the 2.4 mg weekly dose (MedCity News, February 2026). The bigger number reflects the longer interval, not a stronger drug.
A long half-life also has a downside. If someone has side effects, the drug takes weeks to clear. How this affects safety management will be one question for the phase 3 trials.
Regulatory status
Status checked on November 7, 2026 using the ClinicalTrials.gov registry:
- Not approved, not filed. No regulator has received an application.
- Phase 3 program. Twelve phase 3 trials are registered:
| Trial | NCT number | Design | Planned size | Status |
|---|---|---|---|---|
| VESPER-4 | NCT07311850 | Weekly, obesity or overweight without diabetes | 3,578 | Enrollment complete |
| Type 2 diabetes, weekly | NCT07400653 | Weekly, with type 2 diabetes | 1,078 | Enrollment complete |
| Monthly maintenance | NCT07595549 | Monthly, with or without type 2 diabetes | 954 | Recruiting |
| Sleep apnea, monthly (first trial) | NCT07823608 | Monthly, obstructive sleep apnea | 258 | Recruiting |
| VESPER-OSA 2 | NCT07881757 | Monthly, obstructive sleep apnea | 258 | Recruiting |
| Switch study | NCT07845500 | Switch from weekly semaglutide or tirzepatide to monthly berobenatide | 660 | Recruiting |
| Knee osteoarthritis | NCT07915609 | Weekly, knee osteoarthritis | 756 | Recruiting |
| Knee pain | NCT07919678 | Knee pain with overweight or obesity | 656 | Recruiting |
| Japan, monthly | NCT07794774 | Monthly, Japan | 197 | Recruiting |
| Japan, weekly | NCT07794761 | Weekly, Japan | 180 | Recruiting |
| China, weekly | NCT07792954 | Weekly, China | 300 | Recruiting |
| China, monthly | NCT07874633 | Monthly, China | 432 | Recruiting |
VESPER-4 lists estimated primary completion in September 2027, and the monthly-maintenance trial (NCT07595549) in May 2028. Separately, a phase 2b trial called SOLIS-1 (NCT07575932, 940 participants) tests berobenatide alone and combined with PF-08653945, Pfizer’s long-acting amylin analogue (formerly MET-233i). Pfizer’s November 3, 2026 quarterly results did not give a drug-specific update (Pfizer Q3 2026 release, SEC).
What the research shows
None of the phase 2 results had been published in a peer-reviewed journal by November 7, 2026. The figures below come from company releases, an SEC filing and conference coverage.
Weekly dosing (VESPER-1, phase 2b)
VESPER-1 (NCT06712836) randomized 239 adults with obesity or overweight and no diabetes to placebo or one of four weekly doses for 28 weeks, without dose titration. Mean BMI was about 36, and about two-thirds of participants were women (Metsera VESPER-1 release).
| Weekly dose | n | Placebo-adjusted weight loss at 28 weeks (95% CI) |
|---|---|---|
| 0.4 mg | 54 | 8.1% (5.6–10.6) |
| 0.6 mg | 54 | 10.0% (7.6–12.5) |
| 0.9 mg | 53 | 13.0% (10.5–15.5) |
| 1.2 mg | 54 | 14.1% (11.6–16.7) |
The best individual result was 26.5% weight loss. Weight was still falling at the end of weekly dosing. In a 32-week extension, participants first given placebo were moved up to 2.4 mg weekly. They reached 15.9% weight loss at week 60 of the study (not placebo-adjusted, and after only 32 weeks on the drug), with no plateau (Cleveland Clinic Journal of Medicine, ADA 2026 report).
Monthly dosing (VESPER-3, phase 2b)
VESPER-3 (NCT06973720) enrolled 268 adults. They received 12 weekly doses, with or without titration, and then switched to monthly maintenance through week 28. At week 28, placebo-adjusted weight loss was about 10% on a 3.2 mg monthly dose and 12.3% on a 4.8 mg monthly dose (MedCity News). All four regimens beat placebo, and no plateau was seen at week 28 (CCJM report). The trial follows participants to week 64.
For context only: these are 28-week results. Approved drugs are judged on 68–72-week trials, so cross-trial comparisons are unreliable. An analyst quoted in trade coverage called the early data “slightly inferior” to tirzepatide at the same time point (MedCity News).
Body composition: no data yet
No DXA, MRI or other body-composition results have been released for berobenatide. A search of all berobenatide, MET097 and PF-08653944 records on ClinicalTrials.gov on November 7, 2026 found no listed outcome for lean mass, fat-free mass, DXA or muscle. In the meantime, the best guide is the class as a whole. Across 40 DXA reports of GLP-1-based drugs, fat-free mass made up a mean of 29.1% of weight lost (Dubin et al., Obesity 2026). A meta-analysis found 33.3% for incretin drugs vs 7.7% for diet combined with exercise (Busk-Cirera et al., Diabetes Obes Metab 2026).
Metsera’s filings argued that adding an amylin analogue might help preserve lean mass. They cited only preclinical evidence and said “the relevance of these findings to human subjects remains uncertain” (Metsera 2024 Form 10-K). The SOLIS-1 combination trial may eventually address this, but its registered outcomes do not include body composition.
Use alongside testosterone or anabolic steroids
No study has combined berobenatide with TRT or anabolic-androgenic steroids. For GLP-1 drugs in general, a 2026 review found no randomized trials of combined GLP-1 and TRT therapy on body composition (Canal de Velasco et al., Cureus 2026). A meta-analysis of four small studies found that GLP-1 drugs were associated with higher bioavailable testosterone, probably through weight loss and better insulin sensitivity (Orra et al., BMC Urol 2025). Neither finding is specific to berobenatide.
Side effects and risks
Gastrointestinal effects
As with other GLP-1 drugs, nausea, vomiting and diarrhea are the main side effects. In VESPER-1, given without titration, the excess over placebo was 4–23 percentage points for nausea, 4–15 points for vomiting and 0–13 points for diarrhea, depending on dose. Total study discontinuation was 2.9%, and 2 of 239 participants stopped for adverse events (Metsera VESPER-1 release).
An interim look at VESPER-3 after 12 weekly doses compared titration schemes. Figures are risk differences vs placebo (placebo rates: nausea 11.3%, vomiting 1.9%, diarrhea 5.7%):
| Titration arm | Nausea | Vomiting | Diarrhea |
|---|---|---|---|
| 0.4 → 0.8 mg | +14.6 points | +9.2 points | +11.0 points |
| 0.4 → 0.8 → 1.2 mg | +12.8 points | +11.1 points | −0.1 points |
| 0.6 → 1.2 mg | +18.9 points | +17.0 points | +3.8 points |
| 0.8 mg (no titration) | +23.9 points | +14.8 points | −0.1 points |
Each arm had 53–54 participants, so the confidence intervals are wide. In the monthly phase, gastrointestinal events were reported as mostly mild or moderate, with no more than one case of severe nausea or vomiting per dose group and no severe diarrhea (MedCity News).
Gaps in the safety data
- Small, short trials. The completed trials enrolled about 240–270 people each and reported 28-week primary results.
- No peer-reviewed data. Rare events such as pancreatitis, gallbladder disease or heart-rhythm effects cannot be judged yet.
- Slow clearance. With a half-life of about 16 days, side effects may last longer after stopping than with weekly drugs.
- Class warnings. Approved GLP-1 drugs carry warnings for thyroid C-cell tumors in rodents, pancreatitis and gallbladder disease (Wegovy label, DailyMed). Whether these apply to berobenatide is not yet known.
Unregulated products
Berobenatide is available only inside Pfizer’s trials. Anything sold online as “MET-097i,” “MET-097” or “berobenatide” is not Pfizer’s product, and its identity, dose, purity and sterility cannot be assumed.
Legal status and use in sport
Berobenatide is not named on the WADA Prohibited List, and GLP-1 drugs as a class are not prohibited. However, S0 bans “any pharmacological substance” with “no current approval by any governmental regulatory health authority for human therapeutic use,” including “drugs under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an investigational drug, berobenatide falls under S0 and is prohibited at all times. Its status would change only if a regulator approves it.
WADA’s 2026 Monitoring Program tracks markers of semaglutide and tirzepatide only (WADA 2026 Monitoring Program). We found no published anti-doping detection method specific to berobenatide.
Key takeaways
- A monthly GLP-1 candidate. Berobenatide is a single-receptor GLP-1 agonist with a half-life of about 380 hours, designed for weekly or monthly injection.
- Phase 3, not approved. Pfizer, which bought Metsera in November 2025, has 12 phase 3 trials registered as of November 7, 2026 and has said it is targeting approvals starting in 2028.
- Phase 2b efficacy. Weekly doses gave 8.1–14.1% placebo-adjusted weight loss at 28 weeks; monthly maintenance gave about 10–12.3%.
- Low dropout so far. In VESPER-1, 2 of 239 participants stopped for side effects, but nausea and vomiting were still common at higher doses.
- No lean-mass data. No body-composition results exist, and no registered trial measures lean mass.
- Banned in tested sport. As an unapproved drug it falls under WADA S0; “research” products sold online are not the trial drug.
Sources
- Metsera. Metsera reports positive phase 2b results for first- and best-in-class ultra-long acting GLP-1 RA candidate MET-097i, enabling rapid transition into phase 3. Press release (Form 8-K, Exhibit 99.1), September 29, 2025. SEC.
- Metsera, Inc. Annual report on Form 10-K for fiscal year 2024. SEC.
- Pfizer. Pfizer completes acquisition of Metsera. Press release, November 13, 2025. BioSpace.
- MedCity News. Pfizer’s monthly injectable GLP-1 obesity and weight-loss plan. February 2026. MedCity News.
- Cleveland Clinic Journal of Medicine. Berobenatide weight loss benefit maintained in shift to monthly dosing, phase 2b data show (ADA 2026 report). June 2026. CCJM.
- Pfizer. Pfizer reports third-quarter 2026 results (Form 8-K, Exhibit 99). November 3, 2026. SEC.
- ClinicalTrials.gov. A phase 2b study to examine the safety and efficacy of once-weekly MET097 in adults with obesity or overweight (VESPER-1). NCT06712836. ClinicalTrials.gov.
- ClinicalTrials.gov. A phase 2b study to evaluate the efficacy and safety of once-monthly MET097 in adults with obesity or overweight (VESPER-3). NCT06973720. ClinicalTrials.gov.
- ClinicalTrials.gov. Efficacy and safety of MET097 once-weekly in people with overweight or obesity (VESPER-4). NCT07311850. ClinicalTrials.gov.
- ClinicalTrials.gov. A study to learn about the study medicine called berobenatide (PF-08653944) in people with overweight or obesity (once-monthly phase 3). NCT07595549. ClinicalTrials.gov.
- ClinicalTrials.gov. Other berobenatide phase 3 trials: NCT07400653, NCT07823608, NCT07881757, NCT07845500, NCT07915609, NCT07919678, NCT07794774, NCT07794761, NCT07792954, NCT07874633; phase 2b SOLIS-1, NCT07575932. ClinicalTrials.gov.
- Dubin RL, Sanders TN, Schwab HM, et al. Glucagon-Like Peptide-1 Receptor Agonist-Based Agents and Body Composition: Filling More Gaps. Obesity (Silver Spring). 2026;34(Suppl 2):51–63. PubMed.
- Busk-Cirera L, Carlsen IØ, Madsen LB, et al. Effects of Incretin-Based Therapies, Diet and Exercise Interventions, and Bariatric Surgery on Fat-Free Mass in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis. Diabetes Obes Metab. 2026;28(9):7737–7751. PubMed.
- Canal de Velasco LM, González Flores JE, Kraus Fischer G, et al. Testosterone Replacement Therapy as a Potential Strategy to Preserve Lean Mass in Men With Persistently Low Serum Testosterone Receiving GLP-1 Receptor Agonists: A Narrative Review. Cureus. 2026;18(3):e105734. PubMed.
- Orra SH, Martinez JVN, Porto BC, et al. Effect of GLP-1 agonists on testosterone levels: a systematic review and meta-analysis. BMC Urol. 2025;25(1):311. PubMed.
- Novo Nordisk. Wegovy (semaglutide) injection prescribing information. Revised June 2026. DailyMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.
- World Anti-Doping Agency. The 2026 Monitoring Program. WADA.