Also known as: PF-3944, MET-097
Obesity and overweight with comorbidities
Amount
9.6 mg (monthly target dose)
Frequency
Once monthly
Duration
28 weeks (Phase 2b)
Route
SCSchedule
Once monthly (after initial weekly transition)
Timing
Weekly-to-monthly transition protocol used in clinical trials; initial weekly dosing before transitioning to once-monthly injection
Duration
Ongoing
Repeatable
Yes
Fasting glucose and HbA1c
When: Baseline
Why: Baseline glycemic status
Lipid panel
When: Baseline
Why: Baseline cardiovascular risk markers
Fasting glucose and HbA1c
When: 12 weeks
Why: Monitor glycemic changes
Lipid panel
When: 28 weeks
Why: Assess metabolic improvements
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MET-097i (PF-3944) is an ultra-long-acting GLP-1 receptor agonist developed by Metsera using the proprietary HALO (Half-life Augmented Linker and Oligomer) platform. With a half-life of approximately 380 hours, it enables once-monthly subcutaneous dosing, significantly reducing injection burden compared to weekly GLP-1 agonists. Pfizer acquired Metsera for approximately $10 billion, signaling strong pharmaceutical industry confidence in the asset.
MET-097i activates the GLP-1 receptor to suppress appetite, slow gastric emptying, and improve glucose homeostasis. It is described as a biased GLP-1 agonist, meaning it preferentially activates certain intracellular signaling pathways (such as G-protein signaling) over others (such as beta-arrestin recruitment). This biased agonism may contribute to reduced gastrointestinal side effects compared to unbiased GLP-1 agonists.
The HALO platform conjugates a GLP-1 peptide to a proprietary oligomeric carrier via a specialized linker, creating a construct with dramatically extended pharmacokinetics. This technology is modular and could be applied to other peptide therapeutics beyond GLP-1.
The VESPER clinical program is evaluating MET-097i across multiple studies. VESPER-3, the Phase 2b trial, used a weekly-to-monthly transition protocol achieving 12.3% weight loss at 28 weeks. Modeling suggests that direct monthly dosing at 9.6 mg could achieve approximately 16% weight loss.
MET-097i is investigational and not approved by any regulatory authority. All data come from Phase 1/2b trials. Long-term safety and optimal dosing regimen are still being established.
VESPER-3 Phase 2b Study of MET-097i in Adults with Obesity, published in Conference presentation (Metsera/Pfizer) (Metsera investigators, 2025):
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See real-world usage patterns alongside the clinical evidence above. Community-sourced, not clinically verified.
0View community protocolsMariTide (maridebart cafraglutide): Amgen antibody-peptide conjugate combining GLP-1 agonism with GIPR antagonism. Monthly dosing. Phase 2 showed up to 16.2% weight loss at 52 weeks.
Semaglutide: FDA-approved GLP-1 agonist for weight loss and diabetes. Covers STEP/SUSTAIN trials, Ozempic vs Wegovy dosing, and cardiovascular benefits.
Tirzepatide: FDA-approved dual GIP/GLP-1 agonist with up to 22.5% weight loss. Covers SURPASS/SURMOUNT trials, dosing, and semaglutide comparison.
Zovaglutide (ZT-002): first once-monthly GLP-1 agonist for obesity by QL Biopharm. Phase 2 showed 13.8% weight loss at 24 weeks. Phase 3 initiated.
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.
MET-097i represents a potentially disruptive approach to GLP-1 therapy with its ultra-long half-life enabling once-monthly dosing. Phase 2b data shows competitive weight loss (14.1% placebo-subtracted), and the convenience of monthly dosing could significantly improve treatment adherence. However, semaglutide remains the gold standard with proven efficacy, cardiovascular benefit, 7+ years of safety data, multiple formulations, and FDA approval. MET-097i's clinical value will ultimately depend on Phase 3 confirmation and whether the convenience advantage translates to better real-world outcomes. Pfizer's acquisition of Metsera signals strong commercial interest in the once-monthly GLP-1 concept.
MET-097i and zovaglutide are both investigational once-monthly GLP-1 agonists with promising Phase 2 data showing competitive weight loss and encouraging tolerability. Neither is approved. MET-097i has the advantage of Pfizer's acquisition and development resources (approximately $10 billion deal), a novel biased agonist mechanism via the HALO platform, and a clear Phase 3 pathway. Zovaglutide has the advantage of a true once-monthly dosing design from the start (rather than weekly-to-monthly transition) and an exceptionally low GI discontinuation rate (1.3%). Weight loss efficacy appears comparable between the two based on Phase 2 data. The race to become the first approved monthly GLP-1 agonist will likely be determined by Phase 3 execution speed and regulatory strategy.
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