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Maridebart cafraglutide

Also known as

MariTide · AMG 133 · AMG-133 · AMG133 · maridebart cafraglutide · MariTide (Amgen) · GIPR antagonist / GLP-1 agonist conjugate · GIPR-Ab + dual GLP-1 peptide conjugate · peptide–antibody conjugate obesity candidate · monthly MariTide (pipeline shorthand)

Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.

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Peptide Niche talk Systemic SubQ Metabolic / GLP-1 class

Systemic — a subcutaneous peptide–antibody conjugate studied for appetite, weight, glycemic and cardiometabolic effects.

What people say Maridebart cafraglutide, or MariTide/AMG 133, is Amgen's investigational GIP-receptor-antagonist antibody conjugated to two GLP-1 agonist peptides. It is a long-acting biologic, not a commodity peptide vial. Doses people talk about
Phase 2 fixed monthly arms140 / 280 / 420 mg SC every 4 weeks

Randomized obesity and obesity-with-diabetes arms without dose escalation.

Phase 2 fixed less-frequent arm420 mg SC every 8 weeks

Randomized obesity arm without dose escalation.

Phase 2 escalation arms70 mg start → 420 mg SC every 4 weeks

The randomized study used 4-week or 12-week escalation periods; this is a descriptive trial schedule, not a recommendation.

Phase 1 multiple-dose cohorts140 / 280 / 420 mg SC every 4 weeks

Three doses on days 1, 29 and 57; not an approved regimen.

The participant explicitly said neither they nor their team knew the dose. The profile's 140–420 mg quantities describe a proprietary peptide–antibody conjugate and are not transferable to ordinary peptide-vial arithmetic.

Half-life & effect duration

Half-life in the body
  • Intact MariTide / AMG 133About 14–16 days
  • Total antibody signalAbout 21–24 days
Felt duration people report
  • One trial accountWeight changes over more than a year, with lasting constipation
  • After one injectionNo consistent felt window reported
Timing context & sources
How it may feel Trial-level experience is dominated by early GI burden, which was lower with dose escalation and lower starts. One blinded trial participant reported over 60 lb lost in a little over a year and lasting constipation, but neither the participant nor team knew the assigned dose.
Cycles people discuss This is chronic trial therapy, not a short peptide cycle. Amgen says the large majority of Part 2 participants—people who had lost at least 15% in Part 1—maintained that loss for another 52 weeks on lower monthly or quarterly schedules, but off-treatment durability remains unresolved. Timing Trials use scheduled SC injections every four weeks, with an every-eight-week fixed arm and an every-twelve-week maintenance arm also studied. This is a chronic calendar with escalation in some programs, not a short self-directed cycle. Stacks The clinical comparator conversation is semaglutide, tirzepatide and retatrutide; concurrent incretin stacking lacks supporting MariTide trial evidence and would not reproduce the proprietary biologic. Watch for Investigational status: Not approved; Phase 3 efficacy, safety, and outcomes still the gate for any future clinical use claim.
Related
SemaglutideTirzepatideRetatrutideSurvodutideCagrilintide

Tap a line to jump into the full notes. Research only — may be wrong.

Timing context & sources

Half-life in the body

Human Phase 1 measured an approximately 14–16 day half-life for intact AMG 133.

The separate total-AMG 133 assay, which also counts antibody lacking attached GLP-1 peptide, measured about 21–24 days; median peak concentration was around days 4–7.

Small early-phase obesity cohorts; intact and total assays are not interchangeable, and no community product can be assumed equivalent to the clinical biologic.

  • Véniant et al. — AMG 133 preclinical and Phase 1 study (opens in a new tab)Clinical PK section: 21–840 mg SAD and 140/280/420 mg MAD cohorts; median Tmax about 4–7 days, intact half-life about 14–16 days and total-AMG 133 half-life about 21–24 days.Small Phase 1 obesity cohorts; article also contains mouse and monkey PK that must not be substituted for human values, and intact versus total assays differ.

Felt duration people report

One participant described more than 60 lb lost over a little more than a year and lasting constipation; randomized Phase 2 data show wide individual and regimen-level variation.

The participant received monthly clinic injections under close monitoring and explicitly said assigned dose was unknown to both participant and team.

Single unverifiable forum identity in a blinded study; dose and allocation are unknown, and weight change does not establish a standard felt onset.

  • r/GLP1ResearchTalk — Blinded MariTide trial experience (opens in a new tab)Visible participant comments: monthly clinic injections, a little over one year, more than 60 lb lost, constipation as lasting side effect, close monitoring, and explicit statement that both participant and team were blinded to dose.Self-identified trial participation is not independently verified; dose and allocation are unknown, and later dose-range guesses remain guesses.
  • Jastreboff et al. — Once-monthly maridebart cafraglutide Phase 2 trial (opens in a new tab)Randomized dose-ranging trial methods and abstract: 592 participants; 140/280/420 mg every 4 weeks, 420 mg every 8 weeks, and 70→420 mg escalation arms; GI events lower with escalation and lower starts.Amgen-funded Phase 2 trial; abstract-level public record does not expose every arm-level adverse-event detail or individual experience.

Other context in this card

  • Amgen 2025 annual report — MariTide program update (opens in a new tab)MariTide section: Part 2 completed in January 2026; sponsor reports that the large majority of Part 2 participants—people who had lost at least 15% in Part 1—maintained that loss for another 52 weeks on lower monthly or quarterly doses; global Phase 3 studies underway.Sponsor annual-report summary rather than a peer-reviewed full Part 2 paper; arm-level data and off-treatment interpretation remain limited.

What people say 13

  • Same cohort — treatment-policy / ITT estimand: Mean change ~−12.3% to −16.2% vs −2.5% placebo — lower than efficacy estimand because early discontinuations are counted more conservatively. trial
  • Weight loss — obesity + T2D (Phase 2 Part 1, efficacy estimand): Up to ~−17.0% (range ~−12.1% to −17.0% across arms) vs −1.4% placebo. trial
  • Obesity + T2D — treatment-policy estimand: ~−8.4% to −12.3% vs −1.7% placebo. trial
  • No clear 52-week plateau (Part 1): Weight-loss curves described as not plateaued by week 52 — used to argue potential for further loss with continued treatment. trial
  • HbA1c (obesity + T2D): Efficacy-estimand reductions up to ~2.2 percentage points; treatment-policy mean change about −1.2 to −1.6 pp vs ~+0.1 pp placebo. trial
  • Cardiometabolic package (Phase 2 pre-specified): Improvements reported in waist circumference, blood pressure, high-sensitivity CRP, and select lipid parameters alongside weight loss. trial
  • Phase 1 MAD durability signal: Highest MAD arm (420 mg SC every 4 weeks × 3 doses) ~−14.5% body weight by ~day 85 vs ~+1.5% placebo; ~−11.2% still reported ~150 days after the last dose in that high-dose group — durability talk that fueled “maybe not lifelong weekly shots” narratives. trial
  • Phase 1 MAD dose steps: 140 mg q4wk ~−7.4% after three doses (~day 78); 420 mg q4wk ~−14.5% by day 85 (exploratory weight endpoints). trial
  • Dosing-frequency benefit (design claim): Half-life and PD support monthly or less-frequent SC schedules vs daily/weekly approved incretins — adherence and injection-burden are the main patient-facing pitch. trial
  • Preclinical: Obese mice and cynomolgus monkeys — weight reduction and improved metabolic markers with GIPR-Ab + GLP-1 conjugate designs before human trials. animal
  • Community framing: “Next-wave monthly shot,” “GIP blocker not GIP booster,” and “could maintain with q8–q12 week dosing someday” — mechanism and frequency hype more than dense first-person logs. forum
  • Autoinjector talk (sponsor): Expected single-dose handheld autoinjector for monthly or less-frequent administration if commercialized — not available as consumer product yet. trial
  • Weight loss — obesity without T2D (Phase 2 Part 1, efficacy estimand): Mean body-weight change at 52 weeks ranged ~−16.3% to −19.9% with MariTide vs −2.6% placebo; Amgen headline framing “up to ~20% average weight loss.” trial

Doses people talk about 14

  • Phase 1 SAD: Single ascending SC doses roughly 21 mg to 840 mg (seven cohorts; n=37 drug / n=12 placebo reported). trial
  • Phase 1 MAD: 140, 280, or 420 mg SC every 4 weeks on days 1, 29, and 57 (three doses); 420 mg arm had incomplete completion of all three doses in some participants. trial
  • Phase 1 PK-LDI (low-dose initiation, NCT06976372): Day 1 start 21 mg, 35 mg, or 70 mg → 70 mg on day 15 → 350 mg on day 29; primary analysis through ~day 43; n=121 safety population. trial
  • PK-LDI vomiting incidence (primary analysis): ~24.4% on 21→70→350 mg path and ~22.5% on 35→70→350 mg path; sponsor reported no GI-related discontinuations in that study. trial
  • Part 2 entry bar: At least ~15% weight loss at week 52 and still taking investigational product; >90% of eligible participants chose to continue into Part 2 per Amgen. trial
  • Route: Subcutaneous injection only in all public clinical programs — no oral maridebart consumer/trial product narrative. trial
  • Phase 2 Part 1 — obesity cohort fixed monthly (no escalation): 140 mg, 280 mg, or 420 mg SC every 4 weeks. trial
  • Phase 2 Part 1 — less-frequent fixed arm: 420 mg SC every 8 weeks without dose escalation (obesity cohort). trial
  • Phase 2 Part 1 — escalation arms (obesity): Start 70 mg, target 420 mg every 4 weeks, escalated over either a 4-week or a 12-week dose-escalation period. trial
  • Phase 2 Part 1 — obesity + T2D cohort: 140, 280, or 420 mg SC every 4 weeks, all without dose escalation (plus placebo). trial
  • Phase 2 randomization scale: Obesity cohort 465 participants across seven active/placebo arms; obesity-diabetes cohort 127; total enrolled 592. trial
  • Phase 3 MARITIME chronic weight management (72-week studies, public design): Randomization to one of three target maintenance doses after an optimized ~8-week escalation: start 21 mg → 35 mg → 70 mg, then assigned maintenance. Exact maintenance mg targets in public materials are described as three targets informed by Phase 2/PK-LDI (not always listed as single fixed public numbers in press copy). trial
  • Phase 2 Part 2 maintenance / durability arms: After Part 1, eligible completers re-randomized (pooled then stratified by prior dose) to placebo or fixed monthly 70 mg, 140 mg, or 420 mg, or 420 mg every 12 weeks — tests continued loss, lower/less-frequent maintenance, and stop. trial
  • Framing: Published trial and pipeline dose ranges only — not medical advice, not approved labeling, not a consumer or research-chem protocol. trial

How it may feel 8

  • Injection cadence feel: Calendar monthly (or q8wk / q12wk arms) rather than weekly pen day — different “routine” than sema/tirz users describe. forum
  • Months 1–3: Progressive weight loss in Phase 1 MAD and Phase 2; few public first-person “food noise diary” threads compared with approved GLP-1s. forum
  • First dose / early weeks: GI symptoms (nausea, vomiting, constipation) are front-loaded and class-typical; high fixed starts without titration were especially rough in Phase 2. trial
  • Through ~52 weeks (Phase 2 Part 1): Continued scale drop without a clear one-year plateau in aggregate curves; individual variance still large. trial
  • Year 2 (completed Phase 2 Part 2): Amgen reported that the large majority of Part 2 participants—people who had lost at least 15% in Part 1—maintained that loss for another 52 weeks on lower monthly or quarterly regimens; this sponsor summary is not a Phase 3 result. trial
  • After last dose (Phase 1 high-dose signal): Substantial weight reduction persisted for months in the 420 mg MAD follow-up window — community often cites this as “stickier” than short-acting peptides, but Phase 2/3 stop-regain data are the real answer and still maturing. trial
  • Early GI burden: Fixed high-dose starts produced more GI events and discontinuations; the randomized Phase 2 report found lower rates with dose escalation and lower starting doses. trial
  • Weeks 1–4 (escalation path): Low-dose starts + multi-step titration (Phase 2 70→420 mg over 4 or 12 weeks; PK-LDI and Phase 3 21→35→70 mg style) cut early GI burden without clear efficacy compromise in sponsor framing. trial

Cycles people discuss 6

  • Regimen length honesty: Any future real-world use, if approved, would likely be long-horizon chronic therapy plus lifestyle support — not a 4-week cut cycle. forum
  • Not a research-peptide blast/cruise: Phase 2 Part 1 is 52 weeks of chronic scheduled dosing — classic 8-on/4-off peptide cycling is not the clinical pattern. trial
  • Chronic weight-management model: Phase 3 MARITIME framed as multi-month (72-week) chronic weight management with titration then maintenance, analogous to approved anti-obesity meds rather than short stacks. trial
  • Maintenance result (Part 2): Amgen reported that the large majority of Part 2 participants—people who had lost at least 15% in Part 1—maintained that loss for another 52 weeks on lower monthly or quarterly dosing; full arm-level detail still needs a complete publication. trial
  • After discontinuation: Phase 1 showed multi-month persistence after high-dose exposure, but durable off-treatment maintenance remains unresolved; the completed Part 2 sponsor summary emphasized lower or quarterly maintenance. trial
  • Obesity-related outcomes extensions: Sponsor communications describe Phase 3 outcomes work in ASCVD, heart failure, and obstructive sleep apnea planned/initiating around the weight-management program — different endpoints, same molecule class program. trial

Timing 9

  • Practical timing: Monthly clinic/home injection calendar — not pre-workout or bedtime peptide timing culture. forum
  • Human half-life (Phase 1): Intact AMG 133 mean t½ ~14–16 days; total AMG 133 (antibody with or without remaining GLP-1 peptides) mean t½ ~21–24 days; ~21-day figure is the most-cited “monthly dosing enabler.” trial
  • Peak exposure: Maximum plasma concentrations typically reached ~day 4–6 (sometimes described ~4–7) after SC dose. trial
  • Why monthly / less frequent: Longer exposure than weekly peptide GLP-1s supports q4wk designs; Phase 2 also tested q8wk and Part 2 tests q12wk 420 mg. trial
  • Intact vs total assays: Intact (GIPR-Ab with ≥1 GLP-1 peptide still attached) clears faster than total antibody signal — biphasic clearance with gradual assay divergence over weeks is described in PK write-ups. trial
  • Animal PK (obese monkeys, SC): Intact half-life roughly ~189–222 h; total ~231–284 h across studied dose ranges — long but assay/dose-dependent. animal
  • Animal PK (mice, IV example): Intact mean t½ ~118 h vs total ~206 h at illustrative 5 mg/kg IV conditions in the Nature Metabolism package. animal
  • Weight PD lag: Multi-week weight change tracks prolonged exposure; not a same-day stimulant “burn.” trial
  • Washout implication: Multi-week residual exposure after a dose means side effects and weight effects do not flip off in 24–48 hours the way short peptides can. trial

More on what it is 7

  • Format note: Clinical product is a long-acting SC biologic conjugate — not BAC-water lyophilized peptide math people use for BPC/TB/CJC. forum
  • Research lens: Discussion is almost entirely trial/pipeline/investor medical coverage; dense DIY self-experiment logs are rare because the molecule is a proprietary multi-hundred-mg clinical biologic, not a commodity research peptide. forum
  • What it is: Amgen investigational peptide–antibody conjugate (MariTide / formerly AMG 133): a fully human monoclonal GIP-receptor antagonist antibody chemically conjugated to two GLP-1 analogue agonist peptides via amino acid linkers (bispecific antibody–peptide design; average MW cited ~153.5 kDa). trial
  • Why people care: Pipeline “monthly (or less frequent) obesity shot” with large Phase 2 weight-loss headlines (~20% efficacy estimand at 52 weeks in non-diabetes obesity) and a mechanism opposite tirzepatide on GIP — block GIPR, activate GLP-1R. trial
  • Mechanism (plain): GLP-1R agonism (two peptide arms) plus GIPR blockade (antibody arm). Amgen cites genetics/preclinical work that GIPR inhibition + GLP-1 activation can outperform either path alone; the human reason both GIP agonism (tirz) and antagonism (MariTide) work with GLP-1 is still discussed as incompletely understood. trial
  • Evidence level: Published Phase 1 and Phase 2 Part 1 plus a low-dose-initiation study; Amgen reported Phase 2 Part 2 complete in January 2026, while global Phase 3 MARITIME studies remain underway. trial
  • What it is not: Not FDA-approved; not a gray-market “research vial” equivalent of the trial biologic; not weekly semaglutide/tirzepatide/retatrutide; not a dual GIP/GLP-1 agonist. trial

Stacks 6

  • Not a forum stack base: Little “MariTide + BPC + CJC + TB” folklore; molecule is discussed as a standalone clinical obesity candidate, not a research-peptide blender. forum
  • Class comparisons people actually search: Semaglutide (weekly GLP-1), tirzepatide (weekly GIP/GLP-1 dual agonist), retatrutide (triple), CagriSema (cagrilintide + sema), survodutide / mazdutide / pemvidutide (other multi-agonists), orforglipron (oral small-molecule GLP-1). forum
  • Polypharmacy caution (future use): If ever co-prescribed near other glucose-lowering or GI-slowing agents, interaction and hypoglycemia/GI risk would be clinical questions — not mapped in gray-market stack charts. forum
  • Maintenance after other incretins: Hypothetical switch/maintenance narratives exist in media; no established public DIY cross-taper protocol from sema/tirz to MariTide because MariTide is not available outside trials. forum
  • Trial co-interventions: Diet, physical activity counseling, and standard obesity-trial lifestyle support co-run with drug — not stimulant stacks. trial
  • Mechanism debate stack talk: “GIP on (tirz) vs GIP off (MariTide)” is the intellectual stack — not co-injection recipes. Both pair with GLP-1 activity; human reconciliation of agonist vs antagonist GIP still incomplete. trial

Storage notes 2

  • No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
  • Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum

Watch for 16

  • GLP-1-class cautions by analogy: Gallbladder disease, dehydration from vomiting/poor intake, delayed gastric emptying interactions, pancreatitis watch-outs, and lean-mass loss with large deficits are discussed the same way as for other incretins — not unique MariTide black-box data. forum
  • Counterfeit / gray-market risk: Any product sold as “MariTide,” “AMG 133 research peptide,” or “monthly GIP antagonist” outside authorized trials has extreme identity, dose, sterility, and immunogenicity uncertainty — hundred-mg clinical biologic is not a typical UGL peptide. forum
  • GI class effects (dominant): Nausea, vomiting, constipation most frequently reported; mostly mild to moderate and concentrated around initial dosing. trial
  • Vomiting without titration (Phase 2): Very high rates on aggressive fixed / no-escalation arms — public NEJM-linked coverage cited vomiting as high as ~92% in the 420 mg every-8-weeks no-escalation obesity arm vs ~43% in a 4-week dose-escalation arm (lowest among those compared). trial
  • GI discontinuation without escalation: About 12–27% of participants in no-escalation obesity arms stopped for GI events in public summaries. trial
  • GI discontinuation with escalation: Dose-escalation arms lower — up to ~7.8% GI-related discontinuations (any-AE discontinuations in escalation arms also described ~11% in some secondary coverage). trial
  • Obesity + diabetes cohort discontinuations (no escalation): Roughly ~6–16% GI-related discontinuation range cited in medical press for that cohort. trial
  • PK-LDI tolerability: With lower starts (21 or 35 mg paths into 70 then 350 mg), vomiting incidence ~22–24% and zero GI discontinuations reported in the primary analysis window. trial
  • Active GI solicitation: Phase 2 used MINVR (modified index of nausea/vomiting/retching) daily patient reporting in addition to standard AE capture — can surface more GI signal than passive reporting alone. trial
  • Phase 1 labs/ECG: No notable between-group differences highlighted for electrolytes, kidney function, hematology; no severe/serious AEs attributed as a defining pattern in early Phase 1 summaries; GI events often resolved within ~48 hours after first-dose clusters. trial
  • Immunogenicity: Anti-drug antibodies are monitored as expected for an antibody–peptide conjugate; clinical impact details are study-dependent. trial
  • Heart-rate note (Phase 1 context): Early transient heart-rate discussion appears in preclinical/clinical write-ups; additional sustained tachycardia/palpitations were not a standout narrative after repeat doses in Phase 1 summaries — still monitor class-typical CV signals in later trials. trial
  • Investigational status: Not approved; Phase 3 efficacy, safety, and outcomes still the gate for any future clinical use claim. trial
  • Not risk-free: Strong weight-loss headlines and monthly convenience do not erase high early GI burden on untitrated high doses, discontinuation risk, or open Phase 3/long-term questions. trial
  • Estimand literacy caution: Media “~20%” figures are often efficacy (on-treatment style) estimands; ITT/treatment-policy means are several points lower — important when comparing across drugs and headlines. trial
  • No unexpected safety signals (Phase 2 sponsor/NEJM framing): Safety consistent with GLP-1 class in aggregate statements; still incomplete long-term and outcomes data pending Phase 3. trial

Updated: 2026-08-12

Evidence mix More trial/lab tags than forum tags Full: every bullet (trial + community). Use Scan for a faster bro-science read.
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