MariTide (maridebart cafraglutide, code name AMG 133) is an investigational obesity drug from Amgen. Unlike semaglutide, tirzepatide and retatrutide, it is not a modified peptide alone. It is a fully human monoclonal antibody that blocks the receptor for glucose-dependent insulinotropic polypeptide (GIP), with two glucagon-like peptide-1 (GLP-1) analogue peptides attached to it that activate the GLP-1 receptor (Véniant et al., Nat Metab 2024).
Because the antibody gives it a half-life of roughly two to three weeks, it is studied as an injection given once a month or less often, rather than once a week. In a 52-week phase 2 trial, mean weight loss ranged from 12.3% to 16.2% versus 2.5% with placebo in people with obesity (Jastreboff et al., NEJM 2025). The single most important fact: MariTide is not an approved drug. As of Amgen’s August 2026 update, its phase 3 trials were still ongoing or enrolling (Amgen, Q2 2026).
This page summarizes what the published trials, trial registries and Amgen’s disclosures report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Antibody–peptide conjugate: GIP receptor antagonist antibody plus GLP-1 receptor agonist peptides |
| Developer / code | Amgen; AMG 133; nonproprietary name maridebart cafraglutide |
| Route | Subcutaneous injection (in trials) |
| Doses studied | Phase 1: 21–840 mg single doses, 140–420 mg every 4 weeks; phase 2: 140–420 mg every 4 weeks, or 420 mg every 8 weeks |
| Half-life (phase 1) | About 14–16 days for the intact molecule; 21–24 days for total antibody |
| Molecular weight | About 153,514 Da (average), antibody-sized |
| Approval status | Not approved by the FDA or any other regulator; phase 3 MARITIME program ongoing |
| US controlled-substance status | Not listed in DEA Schedule III (21 CFR 1308.13) |
| WADA status | Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances), prohibited at all times |
What it is
Amgen built MariTide by conjugating a fully human anti-GIPR (GIP receptor) antagonist antibody to two GLP-1 analogue peptides through amino-acid linkers. The average molecular weight is 153,514 Da (Véniant et al., Nat Metab 2024). In cell assays, the molecule fully blocked native GIP signaling at the human GIP receptor and fully activated the human GLP-1 receptor.
The design is described as an “antibody–peptide conjugate.” The antibody supplies the long half-life and the GIP-blocking action, while the attached peptides supply GLP-1 activity (Yie et al., Antib Ther 2026).
The GIP paradox
MariTide does the opposite of tirzepatide at the GIP receptor. Tirzepatide activates the GIP receptor, while MariTide blocks it, yet both produce more weight loss than GLP-1 activation alone. A 2025 review co-written by Amgen and academic authors states that the mechanism behind this “apparent paradox” remains unknown (Rosenkilde et al., Diabetes 2025). The case for blocking GIP rests on:
- mice lacking the GIP receptor, globally or only in the brain, being protected from diet-induced obesity;
- human genome-wide association studies linking lower-function GIP receptor gene variants to lower BMI;
- animal studies in which anti-GIPR antibodies prevented weight gain.
One proposed explanation is that the GIP receptor is readily internalized (pulled into the cell) when an agonist binds it, so sustained agonism may end up reducing receptor signaling much as blocking it does. This remains a hypothesis (Yie et al., Antib Ther 2026).
How it compares with related drugs
| Drug | Action at GIP receptor | Action at GLP-1 receptor | Other targets | Dosing in pivotal or late trials |
|---|---|---|---|---|
| Semaglutide | None | Agonist | None | Once weekly |
| Tirzepatide | Agonist | Agonist | None | Once weekly |
| Retatrutide | Agonist | Agonist | Glucagon receptor agonist | Once weekly |
| MariTide | Antagonist (blocks it) | Agonist | None | Every 4 weeks; every 8 weeks tested |
Source for dosing: the trials cited in “What the research shows” below.
Pharmacokinetics
Phase 1 measured two forms in blood: “intact” drug (antibody with at least one GLP-1 peptide still attached) and “total” drug (antibody with or without peptides) (Véniant et al., Nat Metab 2024).
| Parameter (phase 1, single doses) | Result |
|---|---|
| Time to peak concentration | About 4–7 days after injection |
| Mean half-life, intact drug | About 14–16 days |
| Mean half-life, total drug | About 21–24 days |
| Dose proportionality | Exposure rose roughly in proportion to dose |
The shorter half-life of the intact form means the GLP-1 peptides are gradually lost from the antibody over time. The two half-lives are still close enough to support monthly dosing (Yie et al., Antib Ther 2026). For comparison, semaglutide and tirzepatide are given weekly.
Because it is a large antibody, MariTide likely does not cross the blood–brain barrier. The phase 1 authors note that both target receptors are present outside that barrier, including in the area postrema, a brainstem region involved in appetite and nausea (Véniant et al., Nat Metab 2024).
Regulatory status
- Not approved. Amgen describes MariTide as an investigational product not approved by the FDA (Amgen, November 2024).
- Phase 3 program (MARITIME). MARITIME-1 (3,853 adults with obesity or overweight, no diabetes) and MARITIME-2 (1,105 adults with type 2 diabetes) test three doses against placebo for 72 weeks. The primary endpoint is percent weight change at week 72 (NCT06858839; NCT06858878). In these trials, all participants start at 21 mg, then 35 mg, then 70 mg over 8 weeks before reaching one of the three target doses (Amgen, June 2025).
- Outcome trials. MARITIME-CV is enrolling about 12,800 people with atherosclerotic cardiovascular disease, with cardiovascular death, heart attack or ischemic stroke as the primary endpoint (NCT07037433). Other phase 3 trials cover heart failure, obstructive sleep apnea, and switching from weekly semaglutide or tirzepatide to dosing every 8 weeks or every quarter (Amgen, Q2 2026).
- Head-to-head trial. A phase 3 trial comparing MariTide with semaglutide in type 2 diabetes is registered and not yet recruiting (NCT07866066).
No phase 3 results had been published when this page was written.
What the research shows
Animal studies
In obese mice and obese cynomolgus monkeys, MariTide (or a mouse-specific version) lowered body weight and food intake, along with triglycerides and fasting insulin. A single dose of the mouse version caused its maximum weight loss within 24 hours (Véniant et al., Nat Metab 2024). These are animal results and do not show what happens in people.
Phase 1: first human trial
The randomized, double-blind phase 1 trial enrolled adults with obesity and without diabetes (Véniant et al., Nat Metab 2024). In the single-dose part, 49 people received 21–840 mg or placebo and were followed for up to 150 days. In the multiple-dose part, 26 people received 140, 280 or 420 mg or placebo every 4 weeks (days 1, 29 and 57).
| Group | Mean weight change |
|---|---|
| Single dose, 840 mg | −2.8% at day 6; −8.2% at day 92 |
| Single dose, placebo | −0.5% at day 6; +1.7% at day 92 |
| 140 mg every 4 weeks | −7.4% at day 78 |
| 420 mg every 4 weeks | −14.5% at day 85 |
| Placebo every 4 weeks | +1.5% at day 85 |
In the 420 mg group, weight was still 11.2% below baseline 150 days after the last dose. Only 4 of the 8 people in that group received all three doses: the other 4 withdrew after the first dose because of mild gastrointestinal symptoms. Groups had 6–8 people each, so these results are imprecise.
Phase 2: obesity with or without type 2 diabetes
The phase 2 trial randomized 592 adults to placebo or one of several MariTide regimens for 52 weeks (Jastreboff et al., NEJM 2025). It included two cohorts:
- Obesity cohort: 465 participants; 63% female; mean age 47.9; mean BMI 37.9.
- Obesity-plus-diabetes cohort: 127 participants; 42% female; mean age 55.1; mean BMI 36.5.
Results below use the “treatment policy” estimand, which counts everyone randomized whether or not they stayed on the drug. Per-arm values for the obesity cohort are as tabulated from the NEJM paper by Bassatne and Rizo, Adv Ther 2026.
| Obesity cohort arm (n) | Weight change at 52 weeks | Reached ≥15% loss | Reached ≥20% loss |
|---|---|---|---|
| Placebo (78) | −2.5% | 2.6% | 0% |
| 140 mg every 4 weeks, no escalation (77) | −13.6% | 45.5% | 23.4% |
| 280 mg every 4 weeks, no escalation (77) | −15.5% | 62.3% | 36.4% |
| 420 mg every 4 weeks, no escalation (79) | −14.6% | 54.4% | 30.4% |
| 420 mg every 8 weeks, no escalation (51) | −12.3% | 47.1% | 25.5% |
| 420 mg every 4 weeks, 4-week escalation (51) | −14.1% | 58.8% | 23.5% |
| 420 mg every 4 weeks, 12-week escalation (52) | −16.2% | 61.5% | 38.5% |
Other findings:
- Efficacy estimand. Among people who stayed on treatment, mean weight loss was 16.3–19.9% in the obesity cohort and 12.1–17.0% in the diabetes cohort (Amgen, June 2025).
- No plateau. Amgen reported that weight loss had not leveled off by week 52 (Amgen, November 2024).
- Diabetes cohort. Weight change ranged from −8.4% to −12.3% versus −1.7% with placebo. HbA1c (average blood sugar over about 3 months) fell by 1.2–1.6 percentage points versus a 0.1-point rise with placebo (Jastreboff et al., NEJM 2025). Amgen reported reductions of up to 2.2 points using the efficacy estimand (Amgen, June 2025).
Body composition
Dual-energy X-ray absorptiometry (DXA) measured fat and lean mass (Bassatne and Rizo, Adv Ther 2026):
| Obesity cohort | Change in fat mass | Change in lean mass |
|---|---|---|
| Placebo | −9.1% | −2.1% |
| MariTide arms (range) | −26.2% to −36.8% | −8.6% to −11.6% |
As with other incretin drugs, part of the weight lost was lean mass. Whether this affects strength or function was not reported in the sources we could access.
Maintenance and the diabetes trial (topline only)
- Second year (phase 2 part 2). People who had lost at least 15% of their weight by week 52 could continue for another 52 weeks on a lower monthly dose or a quarterly dose. Amgen reported that “the large majority” kept their weight off, with low rates of nausea and vomiting (Amgen, Q4 2025). Amgen did not release numbers, and the data were not peer-reviewed.
- Type 2 diabetes phase 2. A 409-person trial with HbA1c change at 24 weeks as its primary endpoint (NCT06660173) reported “clinically meaningful” HbA1c and weight reductions with monthly dosing (Amgen, Q4 2025). Amgen did not release figures.
How the weight loss compares
These numbers come from separate trials with different populations, durations and statistical methods. No head-to-head obesity trial has been reported, so they cannot be ranked directly.
| Trial | Drug and dose | Duration | Mean weight change vs placebo |
|---|---|---|---|
| STEP 1 (Wilding et al., NEJM 2021) | Semaglutide 2.4 mg weekly | 68 weeks | −14.9% vs −2.4% |
| SURMOUNT-1 (Jastreboff et al., NEJM 2022) | Tirzepatide 5, 10, 15 mg weekly | 72 weeks | −15.0%, −19.5%, −20.9% vs −3.1% |
| Retatrutide phase 2 (Jastreboff et al., NEJM 2023) | Retatrutide 12 mg weekly | 48 weeks | −24.2% vs −2.1% |
| MariTide phase 2 (Jastreboff et al., NEJM 2025) | 140–420 mg every 4–8 weeks | 52 weeks | −12.3% to −16.2% vs −2.5% |
The main difference is the dosing interval, not a larger effect. MariTide’s phase 2 results fall in the range of the weekly drugs, but it is given 12–13 times a year rather than about 52.
Side effects and risks
MariTide has no prescribing label. Everything below comes from trials with at most about one year of controlled data.
Nausea and vomiting
Gastrointestinal effects were the most common adverse events, as with other GLP-1 drugs, and were strongly tied to the first dose. In phase 1, nausea and vomiting were frequent when people started directly at a full dose, and they generally resolved within 48 hours (Véniant et al., Nat Metab 2024):
| Phase 1 multiple-dose group | Nausea | Vomiting |
|---|---|---|
| Placebo (n = 6) | 17% | 0% |
| 140 mg (n = 6) | 83% | 67% |
| 280 mg (n = 6) | 67% | 83% |
| 420 mg (n = 8) | 100% | 75% |
In phase 2, gastrointestinal events were less frequent when the dose was escalated gradually and the starting dose was lower (Jastreboff et al., NEJM 2025). Amgen reported the following (Amgen, November 2024):
- nausea resolved within a median of 6 days, and vomiting within 1–2 days;
- in the dose-escalation arms, about 11% of participants stopped because of any adverse event, and under 8% because of gastrointestinal events.
This first-dose effect is why phase 3 starts at 21 mg, far below the 420 mg used without escalation in phase 2.
Gallbladder events
In the phase 2 obesity cohort, gallbladder events occurred in 1–6% of people on MariTide versus 0% on placebo, with higher rates at 420 mg (Bassatne and Rizo, Adv Ther 2026). Gallbladder problems are a known risk with rapid weight loss and with other GLP-1 drugs.
Heart rate
In phase 1, heart rate rose after dosing but stayed within the normal range. The rise did not depend on dose, did not grow with the second or third dose, and no tachycardia (abnormally fast heart rate) or palpitations were reported as adverse events (Véniant et al., Nat Metab 2024).
Pancreas and liver enzymes
In phase 1, single cases of raised amylase and lipase (pancreatic enzymes) resolved without clinical consequences. No serious adverse events were reported in that trial.
Bone density
The GIP receptor is present in bone-forming and bone-resorbing cells. Mice lacking the receptor have weaker cortical bone, so blocking it raised a theoretical concern about bone loss (Yie et al., Antib Ther 2026). The same review notes that one human gene variant was linked to lower bone density in early studies, but a study of about 1.2 million people found no link to fractures.
Amgen reported “no association” between MariTide and changes in bone mineral density in phase 2 (Amgen, November 2024). Fracture data from longer, larger trials are not yet available.
Who it has not been studied in
Phase 1 enrolled only men and women who could not become pregnant, aged 18–65 (Véniant et al., Nat Metab 2024). No data exist in pregnancy, children, or people with severe kidney disease. A trial of how the body handles the drug in kidney impairment is listed as completed, with no results posted (NCT07429045).
Long duration of action
Because the half-life is about two to three weeks, side effects cannot be stopped quickly by stopping the drug. In phase 1, weight was still reduced 150 days after the last dose.
Use in sport
MariTide is not named on the WADA Prohibited List. However, the S0 class bans any pharmacological substance not covered elsewhere on the List that has no current approval from any government health authority, including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an unapproved investigational drug, MariTide falls into that class and is prohibited at all times. This could change if a regulator approves it.
It is not listed as a controlled substance in DEA Schedule III (21 CFR 1308.13).
Key takeaways
- A different design. MariTide is an antibody that blocks the GIP receptor with two GLP-1 peptides attached. Tirzepatide and retatrutide activate the GIP receptor instead.
- Monthly or less frequent dosing. A half-life of about 14–16 days for the intact drug supports injections every 4 weeks, and every 8 weeks was also tested.
- Weight loss similar to weekly drugs. Phase 2 showed 12.3–16.2% mean loss at 52 weeks versus 2.5% with placebo, with no plateau reported. No head-to-head obesity trial exists.
- First-dose nausea and vomiting are the main problem. Starting at a full dose caused frequent vomiting, so phase 3 uses gradual escalation from 21 mg.
- Still investigational. Phase 3 trials (MARITIME) were ongoing as of August 2026. Long-term safety, including bone and cardiovascular outcomes, is not yet known.
- Prohibited in sport. It falls under WADA S0 as an unapproved substance.
Sources
- Véniant MM, Lu SC, Atangan L, et al. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab. 2024;6(2):290–303. PubMed.
- Jastreboff AM, Ryan DH, Bays HE, et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. N Engl J Med. 2025;393(9):843–857. PubMed.
- Bassatne A, Rizo I. Future Directions in the Medical Treatment of Obesity: A Narrative Review. Adv Ther. 2026;43(6):2387–2407. PubMed.
- Yie J, Mou Z, Liu X. Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications. Antib Ther. 2026;9(3):367–380. PubMed.
- Rosenkilde MM, George JT, Véniant MM, Holst JJ. GIP Receptor Antagonists in the Pharmacotherapy of Obesity: Physiologic, Genetic, and Clinical Rationale. Diabetes. 2025;74(8):1334–1338. PubMed.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. PubMed.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216. PubMed.
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514–526. PubMed.
- Amgen. Amgen announces robust weight loss with MariTide in people living with obesity or overweight at 52 weeks in a phase 2 study. Press release, November 26, 2024. Amgen.
- Amgen. Results from Amgen’s phase 2 obesity study of monthly MariTide presented at the American Diabetes Association 85th Scientific Sessions. Press release, June 23, 2025. Amgen.
- Amgen. Amgen reports fourth quarter and full year 2025 financial results. Press release, February 2026. Amgen.
- Amgen. Amgen reports second quarter 2026 financial results. Press release, August 4, 2026. Amgen.
- ClinicalTrials.gov. MARITIME-1 (NCT06858839), MARITIME-2 (NCT06858878), MARITIME-CV (NCT07037433), MARITIME-T2D-3 (NCT07866066), phase 2 type 2 diabetes trial (NCT06660173) and kidney impairment trial (NCT07429045). NCT06858839; NCT06858878; NCT07037433; NCT07866066; NCT06660173; NCT07429045.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.
- Electronic Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.