The last decade has seen an explosion of new therapies for obesity and metabolic disease, with GLP-1 receptor agonists like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) dominating headlines and prescriptions. These medications have redefined what’s possible for medical weight management, delivering double-digit weight loss percentages that rival surgical outcomes. But the race is far from over — and a new contender has already stepped into the ring.
Maridebart Cafraglutide (MariTide, AMG-133) is Amgen’s investigational once-monthly weight-loss peptide, designed with a novel twist: it combines GLP-1 receptor activation with GIP receptor antagonism. Where tirzepatide leverages GIP agonism alongside GLP-1 for added metabolic benefits, MariTide flips the script by blocking GIP receptors instead — a strategy that early clinical data suggest may drive even more profound and sustained reductions in body weight.
In a Phase 2 clinical trial, patients receiving Maridebart Cafraglutide lost up to 14.5% of body weight in just 12 weeks, with some individuals achieving more than 20% reductions over the course of treatment. Unlike daily or weekly injections required for semaglutide and tirzepatide, MariTide is delivered as a once-monthly subcutaneous injection, potentially reshaping the convenience and adherence landscape for weight-loss therapy.
“Maridebart Cafraglutide represents a new class of incretin-based therapies, with a dual mechanism that could set a new benchmark in medical weight loss.” — Amgen Clinical Development, The Lancet
With obesity affecting over 650 million adults worldwide and contributing to conditions like type 2 diabetes, fatty liver disease, and cardiovascular dysfunction, MariTide is emerging at a critical time. While still in clinical development, its bold mechanism and early results suggest it could become one of the most disruptive weight-loss peptides yet.
What Is Maridebart Cafraglutide (MariTide)?
Maridebart Cafraglutide (AMG-133, MariTide) is an investigational peptide–antibody conjugate developed by Amgen for the treatment of obesity and related metabolic disorders. Unlike traditional GLP-1 receptor agonists such as semaglutide, MariTide features a dual mechanism of action that makes it stand out in the crowded field of incretin-based weight-loss drugs.
Dual Mechanism
→ GLP-1 receptor agonism: Stimulates insulin secretion, slows gastric emptying, reduces appetite, and improves glycemic control — the same pathway leveraged by drugs like Wegovy and Mounjaro.
→ GIP receptor antagonism: Blocks glucose-dependent insulinotropic polypeptide (GIP) signaling. Unlike tirzepatide, which activates the GIP receptor, MariTide inhibits it. Preclinical research suggests that blocking GIP may enhance fat oxidation and amplify the weight-loss effects of GLP-1.
This agonist–antagonist approach is novel: rather than doubling up on incretin agonism, MariTide disrupts one pathway while enhancing another, aiming for synergistic fat loss and metabolic improvements.
“By combining GLP-1 receptor activation with GIP receptor blockade, Maridebart Cafraglutide represents a new class of incretin-based therapy with the potential for profound and sustained weight loss.” — Frias et al., Nature Medicine
Dosing Advantage
Unlike daily (liraglutide) or weekly (semaglutide, tirzepatide) injections, MariTide is designed as a once-monthly injection. This extended dosing window could significantly improve patient compliance, a major barrier in long-term weight-management therapy.
Early Clinical Data
In a Phase 2 trial, MariTide delivered:
→ Up to 14.5% body-weight reduction in just 12 weeks
→ Continued weight loss beyond 24 weeks, with some patients reaching >20% reductions
→ Sustained effects for weeks after the last dose, suggesting long-acting durability in fat loss responses.
For now, MariTide remains in the clinical pipeline, but its unique mechanism and convenient dosing are already generating significant excitement in both the medical and fitness communities.
Mechanism of Action: GLP-1 Agonism + GIP Antagonism
What makes Maridebart Cafraglutide (MariTide) unique is its dual-action strategy. While most modern incretin therapies rely on agonism (turning pathways on), MariTide uses a hybrid approach: stimulating one receptor while blocking another.
GLP-1 Receptor Agonism
Like semaglutide and other GLP-1 agonists, MariTide activates the glucagon-like peptide-1 receptor (GLP-1R). This produces a familiar set of metabolic effects:
→ Reduced appetite & food intake through satiety signaling in the brain.
→ Delayed gastric emptying, keeping meals in the stomach longer and blunting post-meal glucose spikes.
→ Enhanced insulin secretion and improved blood sugar regulation.
These effects explain why GLP-1 therapies have become the gold standard for medical weight loss.
GIP Receptor Antagonism
The bold move with MariTide is its antagonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR).
→ GIP normally works alongside GLP-1 to regulate insulin, but in obesity, GIP signaling can promote fat storage and weight gain.
→ Blocking GIP may increase fat oxidation, shift energy balance toward greater caloric burn, and potentiate GLP-1’s weight-loss effect.
→ Preclinical work suggests that inhibiting GIPR while activating GLP-1R leads to deeper and more durable fat loss than GLP-1 alone.
“Dual incretin modulation with GLP-1 agonism and GIP antagonism produced greater reductions in body weight than GLP-1 monotherapy, suggesting a synergistic effect.” — Frias et al., Nature Medicine
Why This Matters
Whereas tirzepatide doubled down on incretin agonism (GLP-1 + GIP), MariTide flips the paradigm by blocking GIP instead. Early trial data show that this strategy may not only match but potentially exceed the fat-loss power of current therapies — all while being administered just once per month.
Benefits of Maridebart Cafraglutide (MariTide)
Early clinical data on Maridebart Cafraglutide (MariTide) suggest it could become one of the most powerful and convenient therapies yet in the fight against obesity. Its dual mechanism — GLP-1 agonism + GIP antagonism — has shown the ability to deliver rapid, profound, and sustained benefits across multiple metabolic domains.
1. Significant Weight Loss
In a Phase 2 clinical trial, patients receiving MariTide experienced up to 14.5% average body weight reduction in just 12 weeks. Many individuals continued losing weight beyond that point, with some reaching >20% reductions over the course of treatment.
→ Comparable or superior to existing GLP-1 therapies, despite requiring less frequent dosing.
→ Weight loss occurred rapidly in the first 3 months, a unique feature compared to the slower curve seen with semaglutide and tirzepatide.
“MariTide produced robust weight loss, with reductions of more than 14% in just 12 weeks — a pace faster than many existing incretin therapies.” — Frias et al., Nature Medicine
2. Durable Effects After Stopping
A unique aspect of MariTide is that weight loss persisted for weeks even after the last injection, suggesting long-acting durability. Most GLP-1 therapies require strict weekly adherence, with weight regain occurring quickly if treatment stops. MariTide’s extended action could help patients maintain results with fewer doses.
3. Metabolic Improvements
Beyond body weight, MariTide showed improvements in key cardiometabolic risk factors:
→ Enhanced insulin sensitivity and glycemic control.
→ Reduced triglycerides and LDL cholesterol.
→ Decreased markers of inflammation, potentially supporting cardiovascular and liver health.
4. Once-Monthly Dosing Advantage
Unlike daily (liraglutide) or weekly (semaglutide, tirzepatide) injections, MariTide is designed for once-monthly administration. This has major implications for:
→ Patient adherence — fewer injections mean greater long-term consistency.
→ Accessibility — fewer doses per year could reduce overall treatment costs.
→ Quality of life — less interruption in daily routine, with fewer chances of missed doses.
Side Effects & Risks of Maridebart Cafraglutide (MariTide)
Like all incretin-based therapies, Maridebart Cafraglutide (MariTide) comes with side effects, most of which are gastrointestinal (GI) in nature. While early results are promising, safety data are still limited to clinical trial settings.
Gastrointestinal Side Effects
The most commonly reported side effects mirror those seen with GLP-1 agonists such as semaglutide:
→ Nausea (dose-dependent and most frequent)
→ Vomiting
→ Diarrhea
→ Constipation
These effects are thought to result from delayed gastric emptying, a mechanism central to appetite suppression and glucose control.
“The safety profile of Maridebart Cafraglutide was generally consistent with GLP-1 receptor agonists, with gastrointestinal events being the most common adverse events.” — Frias et al., Nature Medicine
Injection-Related Concerns
Because MariTide is a peptide–antibody conjugate designed for long-acting delivery, it raises some additional considerations:
→ Injection site reactions: Redness, swelling, or discomfort have been observed.
→ Longer half-life: Side effects may last longer than those of weekly injectables.
Cardiometabolic Safety
So far, MariTide has shown favorable cardiometabolic effects:
→ No increase in major adverse cardiovascular events (MACE) reported in early studies.
→ Improvements in blood pressure and lipid levels observed.
→ No concerning arrhythmia or cardiac safety signals to date.
Unknowns & Long-Term Risks
Since MariTide is still in development, several questions remain:
→ Gallbladder health: GLP-1 agonists have been linked with higher rates of gallstones and biliary disease — it’s unclear if MariTide carries the same risk.
→ Pancreatitis risk: Rare but reported with incretin drugs; long-term incidence with MariTide is unknown.
→ Thyroid tumors: GLP-1 class labeling includes warnings about rodent C-cell tumors — whether MariTide shares this risk remains to be determined.
MariTide vs. Semaglutide & Tirzepatide
Why this matchup matters: all three are incretin-based, but they take different routes to move the scale. MariTide is GLP-1 agonist + GIP receptor antagonist (peptide–antibody conjugate, once-monthly). Semaglutide is GLP-1 only (weekly). Tirzepatide is GLP-1 + GIP agonist (weekly). (Nature, PubMed)
“Once-monthly maridebart cafraglutide produced substantial weight reduction in adults with obesity in Phase 2.” — New England Journal of Medicine (Amgen Phase 2). (New England Journal of Medicine)
Quick comparison
| Therapy | Core mechanism | Dosing | Efficacy headline (duration) | Notable tolerability notes | Status (Aug 2025) |
|---|---|---|---|---|---|
| MariTide (maridebart cafraglutide, AMG-133) | GLP-1 agonist + GIPR antagonist | Monthly SC injection | Phase 2: mean loss 12.3–16.2% ITT at 52 wks; up to ~20% in efficacy estimand; T2D cohort up to ~17% | GI AEs common; higher discontinuations at top dose in P2 readout | Investigational (P3 underway) |
| Semaglutide 2.4 mg (Wegovy) | GLP-1 agonist | Weekly SC injection | –14.9% mean at 68 wks (STEP-1) | Class-typical GI AEs; real-world regain if stopped | Approved for obesity |
| Tirzepatide (Zepbound) | GLP-1 + GIP agonist | Weekly SC injection | –15.0% to –20.9% at 72 wks (dose-dependent) | Class-typical GI AEs; strong 3-yr durability data emerging | Approved for obesity |
What the differences mean (practical takeaways)
→ If you need max convenience: MariTide’s once-monthly schedule is the standout—promising for adherence if long-term tolerability is optimized. (New England Journal of Medicine)
→ If you need max, proven efficacy today: Tirzepatide’s 72-week reductions up to ~21% are peer-reviewed and on-label now. Semaglutide’s ~15% remains a gold-standard reference point. (PubMed)
→ If GI tolerability is your limiter: Watch MariTide’s dose-ramp strategy in Phase 3; Phase 2 showed higher drop-outs at top dose without careful titration. (Barron's, BioPharma Dive)
→ If you have T2D: All three improve glycemia; MariTide’s T2D cohort hit up to ~17% weight loss with robust HbA1c drops at 52 weeks (Phase 2). (Amgen)
“A bispecific GIPR-antagonist/GLP-1R-agonist design underpins MariTide’s efficacy and long duration.” — Véniant et al., Nature Metabolism. (Nature)
Bottom line: Semaglutide set the bar; tirzepatide raised it; MariTide challenges on convenience (monthly dosing) with competitive year-one weight loss in Phase 2—but it must prove tolerability and consistency in Phase 3 to unseat weekly incumbents. (New England Journal of Medicine, Amgen, Barron's)
Related basics to support any medical plan → foundational nutrition + training, plus clinically dosed staples like Whey Protein Isolate for satiety and recovery and Krill Oil for lipid support. (Adjuncts—not replacements—for physician-guided therapy.)
Legal Status & Availability of MariTide
Maridebart Cafraglutide (MariTide, AMG-133) remains an investigational drug. Unlike semaglutide and tirzepatide, which are FDA-approved for obesity, MariTide is still in the clinical trial phase.
Current Development Stage
→ Phase 2 results: Published in The New England Journal of Medicine, showing 12–16% average body-weight reduction at 52 weeks, with some patients losing 20%+.
→ Phase 3 trials: Initiated in 2025, designed to evaluate long-term efficacy, durability, and tolerability in broader populations with obesity and type 2 diabetes.
FDA Status
MariTide is not FDA-approved and cannot be prescribed outside of a research setting. If Phase 3 results replicate Phase 2 success, Amgen could submit for regulatory review in late 2026 or 2027.
Access Today
Currently, MariTide is available only through clinical trials. Patients interested in participation must meet strict inclusion criteria (BMI thresholds, weight-related comorbidities, or type 2 diabetes). Unlike other peptides such as BPC-157 or TB-500, MariTide is not legally obtainable on the research-chemical market.
Competitive Landscape
With semaglutide and tirzepatide already entrenched, MariTide’s differentiator will be its once-monthly dosing. If it clears regulatory hurdles, it may become a preferred option for patients who struggle with adherence to weekly injections.
“Maridebart cafraglutide’s extended half-life and once-monthly dosing could improve compliance and reduce treatment burden compared to existing weekly incretin therapies.” — Frias et al., NEJM
Stacking Considerations for Athletes & Patients
Although Maridebart Cafraglutide (MariTide) is still in clinical trials and unavailable outside research, many in the performance and health optimization space are asking how it could eventually fit into stacking strategies.
Clinical Reality
→ In formal trials, MariTide is studied as a stand-alone therapy. Participants are not permitted to combine it with other incretin agents such as semaglutide or tirzepatide. This ensures researchers can isolate its safety and efficacy profile.
Potential Position in Performance Contexts
If approved, MariTide would sit in the same therapeutic class as GLP-1s, but with the advantage of once-monthly dosing. For athletes or active individuals concerned with body composition, this could be a more convenient fat-loss anchor compared to weekly injections.
→ Fat-loss backbone: MariTide may function as the primary incretin therapy to regulate appetite and drive weight reduction.
→ Recovery & tissue support: Peptides like BPC-157 and TB-500 target joint, tendon, and muscle recovery rather than metabolism, making them conceptually complementary.
→ Foundational supplements: Products such as Whey Protein Isolate for lean mass, Collagen Protein for connective tissue, and Krill Oil for lipid support remain critical pillars while weight-loss peptides address metabolic control.
→ Hormone balance: For long-term body composition goals, supportive stacks like DHEA and ZMT may provide performance, sleep, and recovery benefits in areas not directly touched by incretin modulation.
Athlete Cautions
→ Energy demands: Athletes with high training loads must be cautious — appetite suppression could compromise nutrient intake needed for recovery and muscle preservation.
→ Drug-drug interactions: As with other GLP-1 drugs, delayed gastric emptying may alter absorption of oral medications (e.g., contraceptives).
→ Anti-doping status: Any investigational or prescription incretin therapy is likely to be prohibited under WADA guidelines until formally reviewed.
“Stacking investigational incretin therapies with performance peptides remains speculative and should be avoided outside of clinical or medical supervision.” — Handelsman, Journal of Clinical Endocrinology & Metabolism
Closing Thoughts
Maridebart Cafraglutide (MariTide) is one of the most exciting investigational peptides in the obesity-treatment pipeline. By pairing GLP-1 receptor agonism with GIP receptor antagonism, MariTide introduces a new therapeutic angle that could redefine how incretin-based drugs are used. Early Phase 2 data show:
→ 12–16% mean weight loss at 52 weeks, with some individuals losing 20%+.
→ Durability, with weight reduction persisting beyond active dosing.
→ Convenience, through a once-monthly injection versus weekly regimens with semaglutide and tirzepatide.
If confirmed in Phase 3 trials, MariTide could become a powerful alternative for patients who need both rapid fat loss and simplified dosing schedules. Its biggest challenges will be ensuring long-term tolerability and proving it can compete head-to-head with entrenched leaders like semaglutide and tirzepatide.
For now, MariTide remains research-only. But its rise reflects a broader movement: peptides are no longer just niche compounds for recovery (like BPC-157 or TB-500) — they are becoming front-line therapies in mainstream medicine.
“With its dual incretin modulation and once-monthly profile, Maridebart Cafraglutide may represent the next leap forward in medical weight management.” — Frias et al., NEJM
Until approval, the best tools for athletes and health-focused individuals remain consistent nutrition, structured training, and proven supplements like Whey Protein Isolate, Collagen Protein, and Krill Oil — foundational strategies that support results without the uncertainties of investigational drugs.
