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FAT LOSSNON-PEPTIDEPhase IIGLP-1 AGONISTWEIGHT LOSSOBESITY

Berobenatide

Also known as: PF-3944 · PF'3944 · PF-08653944 · MET-097 · MET-097i

3 views/week 0 citations 0 edits Updated 8/30/2026

Berobenatide is an ultra-long-acting, fully biased GLP-1 receptor agonist peptide originally developed by Metsera and advanced by Pfizer following acquisition, designed for once-monthly maintenance dosing after weekly titration — a fourfold reduction in injection frequency versus weekly GLP-1 agonists.

STRUCTURE

Molecular Composition

FORMULA
Not publicly disclosed
MOL. WEIGHT
Not publicly disclosed
TARGET
GLP-1 receptor (biased)
HALF-LIFE
Ultra-long (supports monthly dosing)
ROUTE
Subcutaneous
STATUS
Phase 2b (VESPER-3)
AMINO ACID CHAIN VISUALIZATION
GLP1
GLP-1 receptor-binding domain
GLP-1R activation, fully biased signalling
NH-CO
FA₂
Double fatty-acid acylation
albumin binding, ultra-long half-life
NH-CO
Bb
Stabilized peptide backbone
proteolytic resistance
SEQUENCEGLP1-FA₂-Bb
MECHANISMS

How It Works

🎯
Fully Biased GLP-1 Receptor Agonism
Described as "fully biased" toward a specific GLP-1 receptor signalling pathway rather than engaging all downstream effectors equally — a design intended to optimize efficacy/tolerability rather than simply maximizing raw receptor activation.
⏱️
Double Acylation for Ultra-Long Half-Life
Patent literature indicates a double fatty-acid acylation strategy, extending albumin-binding half-life enough to support once-monthly dosing — a fourfold reduction in injection frequency versus weekly GLP-1 agonists.
📈
Monthly Dosing Without a Visible Efficacy Plateau
VESPER-3 reported continued weight loss through week 28 with monthly maintenance dosing, addressing a key adherence barrier (injection frequency) without an apparent efficacy tradeoff in this early data.
OVERVIEW

Research Overview

In the Phase 2b VESPER-3 trial, two dosing cohorts of berobenatide reported 10% and 12.3% mean placebo-adjusted weight loss at week 28, with weight loss continuing without a visible plateau. The drug is being developed as a single agent and in combination with an amylin analog (PF-08653945) and a GIPR agonist (MET-034i).

Not yet FDA-approved. Full backbone sequence and molecular weight are not publicly disclosed.

Mechanism of Action

Described in company materials as a "fully biased" GLP-1 receptor agonist — engaging a specific downstream signalling pathway preferentially rather than activating all receptor effectors equally. Patent literature indicates a double fatty-acid acylation strategy that extends albumin-binding half-life enough to support monthly dosing.

DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — PHASE 2B TRIAL REGIMEN
DOSE
0.5 mL injection volume, dose not fully disclosed
FREQUENCY
Weekly titration phase, then once monthly for maintenance
NOTES
Investigational trial dosing from the Phase 2b VESPER-3 study — not an approved or established regimen. Berobenatide is not yet FDA-approved.

Berobenatide (Pfizer/Metsera; also referenced as PF-3944, PF-08653944, and MET-097/MET-097i) is an ultra-long-acting, fully biased GLP-1 receptor agonist peptide originally developed by Metsera and advanced by Pfizer following acquisition. Its defining feature is a double-acylated design (per patent literature) that extends half-life enough to support once-monthly maintenance dosing after an initial weekly titration. In the Phase 2b VESPER-3 trial, two dosing cohorts reported 10% and 12.3% mean placebo-adjusted weight loss at week 28, with a safety profile consistent with the GLP-1 class (predominantly mild-to-moderate GI effects). Full backbone sequence and molecular weight are not publicly disclosed. Also in development in combination with an amylin analog (PF-08653945) and a GIPR agonist (MET-034i).

CYCLING

Cycle Duration Guide

ON CYCLE
Investigational — intended for chronic use if approved, consistent with the GLP-1 drug class
OFF CYCLE
Not established — berobenatide has not completed Phase 3 or received approval

The once-monthly maintenance design is intended to reduce injection burden versus weekly GLP-1 agonists, not to enable cycling on/off.

Phase 2b / investigational — not an approved medicine. Full molecular structure not publicly disclosed.

NOTES

Research Notes

Investigational, Phase 2b (VESPER-3 trial). Full molecular structure not publicly disclosed. Safety profile in early data is consistent with the GLP-1 class (predominantly mild-to-moderate GI effects).
Quick Reference
FORMULA
MOL. WEIGHT0 Da
LENGTH0 amino acids
ORIGINSynthetic peptide (originally Metsera, now Pfizer)
HALF-LIFEUltra-long (supports once-monthly maintenance dosing)
SOLUBILITYNot publicly disclosed
STATUSPhase II
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TAGS
GLP-1 agonistweight lossobesityonce-monthlyultra-long-acting