MariTide (Maridebart Cafraglutide, AMG 133)

Structure: A monoclonal antibody against the GIP receptor with two GLP-1 analogue peptides conjugated to it. That construction is why it behaves like an antibody pharmacokinetically rather than like a peptide, and it is the reason monthly dosing is possible at all.

The mechanism is genuinely contested, and worth understanding before you take a view.

Tirzepatide agonises GIP. MariTide blocks it. Both produce substantial weight loss, which should not be possible if one of them has the direction right and the other has it wrong. The leading explanation is that chronic GIP receptor agonism desensitises the receptor, so tirzepatide may end up functionally closer to antagonism than its label suggests. This is unresolved. Anyone telling you confidently which approach is superior is ahead of the evidence.

Status: investigational (as of August 2026).

• Not approved by the FDA, EMA or TGA.
• Phase 2 published in NEJM, June 2025 (Jastreboff et al.). Phase 3 MARITIME programme ongoing.

Phase 2 dosing arms (n=592, 52 weeks):

• 140mg, 280mg or 420mg every 4 weeks, no dose escalation
• 420mg every 8 weeks, no dose escalation
• 420mg every 4 weeks with 4-week escalation
• 420mg every 4 weeks with 12-week escalation

Results at 52 weeks:

• Obesity cohort (465 participants): -12.3% to -16.2% body weight, against -2.5% for placebo
• Obesity with type 2 diabetes (127 participants): -8.4% to -12.3%, against -1.7% for placebo
• HbA1c in the diabetes cohort: -1.2 to -1.6 percentage points, against +0.1 for placebo
• Weight loss had not plateaued at 52 weeks

Bloodwork implications, which differ from the weekly agonists:

• Timing matters more here. On a weekly drug at steady state, the draw day barely matters. On a monthly one, week 1 and week 4 are different pharmacological states. Standardise your draw to the same point in the cycle every time, or you are measuring the schedule rather than the trend.
• Track HbA1c, fasting glucose and fasting insulin. The glycaemic effect is large enough to show up quickly.
• Track ALT and AST: rapid weight loss shifts hepatic fat and liver enzymes move with it.
• Expect the same lean mass question as every drug in this class. Weigh yourself against creatinine trending down as a crude proxy for muscle loss, and resistance train.

Key notes:

• The once-monthly schedule is the real product differentiator, not the weight loss number, which is broadly comparable to tirzepatide. Adherence is the unsolved problem in this drug class and monthly dosing attacks it directly.
• The first-dose GI burden is the trade-off. You cannot titrate gently inside a month, and the trial data shows the adverse events cluster there.
• Nothing about this is available through legitimate channels yet. Anything sold as MariTide today is not MariTide.

References: When to draw blood on a once-monthly drug, and which markers depend on where in the cycle you test: the MariTide (AMG 133) bloodwork guide.

• Jastreboff, A. M., Ryan, D. H., Bays, H. E., Ebeling, P. R., et al. (2025). Once-monthly maridebart cafraglutide for the treatment of obesity: A phase 2 trial. New England Journal of Medicine, 393(9), 843-857. DOI: 10.1056/NEJMoa2504214