Ania Jastreboff, MD, PhD

Photo courtesy of Yale School of Medicine

Once-monthly maridebart cafraglutide (MariTide, Amgen) demonstrated clinically significant reductions in body weight and glycated hemoglobin (HbA_1c) in adults with obesity, regardless of type 2 diabetes (T2D) status, according to data from a phase 2 clinical trial.¹

The final data from the phase 2 randomized, double-blind, placebo-controlled study were presented as a late-breaking symposium at the American Diabetes Association’s 85th Scientific Sessions and simultaneously published in The New England Journal of Medicine.

"In this Phase 2 study, participants living with obesity treated with MariTide had substantial weight reduction at 52 weeks without reaching a weight plateau," first author Ania Jastreboff, MD, PhD, professor at Yale School of Medicine and director of the Y-Weight Yale Obesity Research Center, said in a press release. "Additionally, robust improvements in HbA1c were observed in participants who had Type 2 diabetes and obesity. These data demonstrate the potential for once monthly or less frequent dosing and are particularly encouraging as we seek sustainable, long-term treatments for people living with obesity, with and without Type 2 diabetes."²

Maridebart cafraglutide is a bispecific glucagon-like peptide-1 (GLP-1) receptor agonism and glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist being developed as a once-monthly therapy for chronic weight management. Its dual mechanism of action and longer half-life support monthly or less frequent administration, according to the researchers.¹

Jastreboff and colleagues enrolled 592 adults with obesity or overweight plus one obesity-related complication. They assessed 2 groups: adults with obesity with T2D (obesity cohort, n=465) and without T2D (obesity-diabetes cohort, n=127). Participants with obesity and without T2D were randomly assigned to receive 140 mg, 280 mg, or 420 mg of maridebart cafraglutide every 4 weeks without dose escalation; 420 mg every 8 weeks without dose escalation; 420 mg every 4 weeks with a 4-week dose escalation; 420 mg every 4 weeks with a 12-week dose escalation; or placebo. Participants with obesity and T2D were randomly assigned to 140 mg, 280 mg, or 420 mg of maridebart cafraglutide every 4 weeks or placebo. Change in body weight from baseline to 1 year was the primary endpoint, according to the study abstract.¹

Findings

In the obesity cohort (mean age, 47.9 years; 63% women; mean BMI, 37.9 kg/m²), the mean percent body weight change at week 52 ranged from –12.3% to –16.2% with maridebart cafraglutide, compared to –2.5% with placebo in the treatment policy estimand (intention-to-treat approach). Under the efficacy estimand, weight loss ranged from –16.3% to –19.9% with maridebart cafraglutide compared to –2.6% with placebo, according to Jastreboff and colleagues.¹

In the obesity–diabetes cohort (mean age, 55.1 years; 42% women; mean BMI, 36.5 kg/m²), maridebart cafraglutide conferred greater weight loss at 1 year than placebo. The mean percent change in body weight according to the treatment policy estimand ranged from –8.4% to –12.3%, compared with –1.7% in the placebo group, investigators found. In the efficacy estimand, weight loss with maridebart cafraglutide ranged from –12.1% to –17%, compared with –1.4% in the placebo group. Additionally, participants in this cohort achieved reductions in HbA_1c of –1.2 to –1.6 percentage points, compared with an increase of 0.1 percentage point in the placebo group, researchers observed.¹

Gastrointestinal (GI) adverse events (AEs)—including nausea, vomiting, and diarrhea—were common in participants receiving maridebart cafraglutide but were less frequent with dose escalation and lower starting doses. No unexpected safety concerns emerged across the treatment arms.

Investigators also reported results from a companion phase 1 pharmacokinetic low-dose initiation study, evaluated 121 participants with obesity or overweight who received escalating doses of maridebart cafraglutide. Participants were randomized to one of three regimens: 21 mg/70 mg/350 mg, 35 mg/70 mg/350 mg, or 70 mg/70 mg/350 mg.

The primary endpoints were pharmacokinetic parameters, including maximum observed concentration (C_max) and area under the concentration-time curve. The incidence of vomiting was 24.4% in the 21/70/350 mg group and 22.5% in the 35/70/350 mg group. No participants discontinued due to GI AEs.

Data from both studies have informed the phase 3 MARITIME program, which includes ongoing 72-week studies to evaluate the efficacy, safety, and tolerability of maridebart cafraglutide in people with obesity or overweight, with and without T2D. All participants are assigned to 1 of 3 target doses, each beginning with a 21 mg dose, followed by 35 mg and then 70 mg, using an 8-week dose-escalation schedule.²

Amgen plans to initiate additional phase 3 trials in 2025 to investigate maridebart cafraglutide in patients with atherosclerotic cardiovascular disease, heart failure, and obstructive sleep apnea.²

“MariTide's monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, Type 2 diabetes and related conditions,” Jay Bradner, MD, executive vice president of Research and Development at Amgen, said in a press release.²

References:

1. Jastreboff AM, Ryan DH, Bays HE, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial. New Engl J Med. Published online June 23, 2025. doi:10.1056/NEJMoa2504214
2. Results from Amgen's phase 2 obesity study of monthly Maritide presented at the American Diabetes Association 85th Scientific Sessions. News release. Amgen. June 23, 2025. Accessed June 26, 2025. https://investors.amgen.com/news-releases/news-release-details/results-amgens-phase-2-obesity-study-monthly-maritide-presented