• MariTide is a novel peptide-antibody conjugate designed to treat obesity and T2Ds by activating GLP-1 receptors and blocking GIP receptors. Its dual mechanism and long half-life may enhance durability and help prevent weight regain. 
• Preclinical studies show greater weight loss with this combined approach than with GLP-1 or GIP targeting alone.

Summary

Amgen’s Phase II trial (NCT05669599) of MariTide (maridebart cafraglutide), a monthly peptide‑antibody conjugate targeting GLP‑1 activation and GIP inhibition, demonstrated strong and ongoing weight loss—including up to ~20% in people with obesity without diabetes and ~17% in those with T2D—alongside cardiometabolic improvements. A lower-dose initiation approach significantly improved tolerability without affecting efficacy. These findings are now guiding a 72-week Phase III program and several outcomes studies.

Trial Design

• Participants: 592 adults; Cohort A: obesity without T2D (n = 465), Cohort B: obesity with T2D (n = 127).
• Dosing arms: three fixed monthly doses (140 mg, 280 mg, 420 mg), a high-dose direct arm, and two dose-escalation arms starting lower (70–420 mg) over four or twelve weeks.
• Evaluation period: 52 weeks plus optional continuation into Part 2 assessing durability and less-frequent dosing.
• Endpoints: Weight change measured via treatment-policy (ITT) and efficacy estimands; additional measures included HbA1c, waist circumference, blood pressure, hs-CRP, and lipids.

Results

• Weight loss: In Cohort A, ITT analyses showed 12.3–16.2% average weight reduction; efficacy estimand reached 16.3–19.9%. In Cohort B, 8.4–12.3% (ITT) and 12.1–17.0% (efficacy). Notably, weight loss remained ongoing at 52 weeks, with no plateau observed.
• Glycemic control: T2D participants had reductions in HbA1c of up to 2.2% points.
• Cardiometabolic benefits: Significant improvements were seen in waist circumference, blood pressure, hs-CRP, and select lipid levels.
• Safety and tolerability: No new safety signals; GI side effects common but mainly mild/moderate. Dose-escalation arms reduced discontinuation due to GI issues: up to 7.8% vs. higher in fixed-dose groups. A companion Phase I PK-LDI study showed vomiting rates of ~22–24% with no GI-driven discontinuations.

KOL Views

“It is encouraging that substantial weight reduction continues through week 52 without signs of plateau. This suggests that sustained, monthly dosing of MariTide could provide long‑term metabolic management in people with and without T2D.” – Expert Opinion

“The Phase II efficacy and safety outcomes, coupled with dose‑escalation tolerability data, directly informed the Phase III MARITIME protocol. Monthly or less frequent administration represents a meaningful advance in real‑world obesity treatment adherence.” – Expert Opinion

Conclusion

MariTide shows promise as a monthly (or less frequent) obesity and T2D treatment—with robust, ongoing weight loss, meaningful cardiometabolic improvements, and enhanced tolerability through dose titration. The data support the design of Amgen’s Phase II MARITIME studies (72-week duration, structured dose escalation) and upcoming trials in cardiovascular disease, heart failure, and sleep apnea.