maridebart cafraglutide (AMG 133) / Amgen - LARVOL DELTA

Once-Monthly Maridebart Cafraglutide Shows Up to 16% Weight Loss (AJMC) - "The trial (NCT05669599) included 592 adults and tested 11 dosing strategies across 2 cohorts, with a primary end point of percent change in body weight between baseline and week 52...Based on the treatment policy estimand—or the intention-to-treat—participants with obesity lost a mean of 12.3% to 16.2% of body weight at 52 weeks across the maridebart cafraglutide subgroups, compared with 2.5% weight loss with placebo. Patients with both obesity and T2D lost a mean 8.4% to 12.3% of their weight with treatment compared with 1.7% with placebo....Participants receiving the once-monthly injection lost substantially more fat mass than those receiving placebo, with reductions of about 26% to 37% in adults with obesity and about 17% to 34% in adults with obesity and T2D, compared with 9% and 4% in the placebo groups, respectively."

P2 data • Obesity • Type 2 Diabetes Mellitus

Once-Monthly Maridebart Cafraglutide in Obesity - A Phase 2 Trial. (PubMed, N Engl J Med) - No abstract available

Journal • P2 data • Genetic Disorders • Obesity

Effect of Maridebart Cafraglutide on the Heart's Electrical Activity (clinicaltrials.gov) - P1 | N=82 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice. (PubMed, Diabetes Obes Metab) - "Our data highlights the distinct metabolic effects of GIPR agonism and antagonism, offering insights for their future application in personalised metabolic disease treatments. Further human studies are needed to understand the long-term metabolic impacts of these therapies."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MARITIME-OSA-2: Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea Not on Positive Airway Pressure (PAP) Therapy (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

A Small Molecule Glucose Dependent Insulinotropic Peptide Receptor Antagonist for Treating Obesity (OBESITY WEEK 2025) - "It's noted that Tirzepatide, a dual GLP-1R and GIP receptor (GIPR) agonist, and Maridebart cafraglutide (as known as MariTide or AMG133), a GIPR antibody fused with peptide GLP-1RA, both demonstrated greater reduction of body weight in humans... Small molecule GIPR antagonists discovered by Eccogene provide potential therapeutic options for treating obesity and other cardiometabolic diseases."

Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Effect of Maridebart Cafraglutide on the Heart's Electrical Activity (clinicaltrials.gov) - P1 | N=82 | Not yet recruiting | Sponsor: Amgen

New P1 trial • Genetic Disorders • Obesity

Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea Not on Positive Airway Pressure (PAP) Therapy (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Comparing the Extent to Which Maridebart Cafraglutide (AMG 133) is Made Available in the Body When Administered Using Two Subcutaneous (SC) Presentations (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: Amgen

New P1 trial • Genetic Disorders • Obesity

MARITIME-OSA-1: Maridebart Cafraglutide Versus Placebo in Adult Participants With Obstructive Sleep Apnea on Positive Airway Pressure Therapy (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Evaluation of GLP1R/GIPR Dual-Target Drugs AMG133 and Tirzepatide in DIO Using Humanized GIPR Mice (OBESITY WEEK 2025) - "Background: Tirzepatide and AMG133 are dual-target drugs targeting GLP1R/GIPR that have shown significant results in treating obesity. Tirzepatide and AMG133 demonstrated superior weight loss efficacy in GIPR-humanized mice, indicating that this model offers a more effective framework for evaluating dual-target GLP1R/GIPR drugs. The humanized model enhances translational potential by addressing limitations in assessing drug efficacy due to low GIPR conservation in wild-type mice."

Preclinical • Genetic Disorders • Obesity

A Study of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus (T2DM) (clinicaltrials.gov) - P2 | N=409 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Jun 2026 ➔ Nov 2026

Trial completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide. (PubMed, Vascul Pharmacol) - "Preclinical and clinical evidence endorses the utilization of glucagon-like peptide-1 receptor (GLP-1R) agonists and novel multi-receptor drugs such as AMG 133, which integrate GLP-1R activation with glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism...Notwithstanding favorable results, peptide therapy encounters obstacles such as administration methods, sustained effectiveness, and expense. Overcoming these obstacles is crucial for the effective implementation of peptide-based treatments in sustained clinical obesity control."

Journal • Review • Addiction (Opioid and Alcohol) • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity. (PubMed, Endocr Rev) - "Maridebart cafraglutide, combining GLP-1R agonism with GIPR antagonism, exemplifies this innovative approach. Glucagon co-agonists like survodutide and mazdutide have demonstrated significant weight loss and improved glycemic control. Amylin-based agents, including CagriSema (cagrilintide + semaglutide) and amycretin, enhance satiety and glycemic outcomes through complementary actions. Further innovation is seen in triple agonists such as retatrutide, which targets GIP, GLP-1, and glucagon receptors to amplify metabolic effects. Meanwhile, the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron and orforglipron, which are resistant to enzymatic degradation, marks a major advance in patient-friendly drug delivery. This review explores the mechanisms, clinical development, and therapeutic potential of these novel agents, excluding already approved drugs like liraglutide, semaglutide, and tirzepatide. We highlight how multi-receptor agonists..."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MARITIME-2: Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (clinicaltrials.gov) - P3 | N=1105 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MARITIME-1: Evaluation of Maridebart Cafraglutide in Adult Participants Without Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (clinicaltrials.gov) - P3 | N=3853 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study to Evaluate the Effect of Maridebart Cafraglutide on Insulin Sensitivity and β-cell Function in Participants With Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Amgen

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

MARITIME-CV: Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (clinicaltrials.gov) - P3 | N=12800 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Atherosclerosis • Cardiovascular • Genetic Disorders • Obesity

MARITIME-HF: Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (clinicaltrials.gov) - P3 | N=5056 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity

A comparison of the metabolic effects of a long-acting GIPR agonist versus a GIPR antagonist (ENDO 2025) - "IntroductionThere is significant interest in targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) for the treatment of type 2 diabetes and obesity...Moreover, both tirzepatide (a GLP-1R/GIPR dual agonist) and AMG133 (a GLP-1R agonist/ GIPR antagonist) appear to outperform GLP-1R mono-agonists with regards to weight loss in clinical trials...Moreover, the observation that GIP108 was unable to prevent GLP-1RA induced emesis, an effect induced by other GIPR agonists, highlights the heterogeneity in CNS responses induced by different GIPR agonists. A comparison of the metabolic effectiveness of both approaches in humans is an important area of future study."

Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MARITIME-HF: Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (clinicaltrials.gov) - P3 | N=5056 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity

Symposium - Once-Monthly MariTide for the Treatment of Obesity in People with or without Type 2 Diabetes—A 52-Week Phase 2 Study (ADA 2025) - No abstract available

P2 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

MariTide & Mother Nature—Rationale for the Long-acting Peptide-antibody Conjugate Molecule, Combining GLP-1 Agonism and GIP Receptor Antagonism (ADA 2025) - No abstract available

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

RESULTS FROM AMGEN'S PHASE 2 OBESITY STUDY OF MONTHLY MARITIDE PRESENTED AT THE AMERICAN DIABETES ASSOCIATION 85TH SCIENTIFIC SESSIONS (PRNewswire) - P2 | N=592 | MariTide (NCT05669599) | Sponsor: Amgen | "In the Phase 2 study, MariTide demonstrated up to ~20% average weight loss in people living with obesity without Type 2 diabetes (T2D) compared with 2.6% in the placebo arm, and up to ~17% average weight loss in people living with obesity with T2D, compared with 1.4% in the placebo arm, per the efficacy estimand. Weight loss had not plateaued by 52 weeks, indicating the potential for further weight reduction. In addition to meaningful weight loss, MariTide demonstrated a robust and sustained reduction in hemoglobin A1c (HbA1c) of up to 2.2% in people living with obesity and T2D. Weight loss with MariTide was also accompanied by improvements across pre-specified cardiometabolic measures, including waist circumference, blood pressure, high-sensitivity C-reactive protein (hs-CRP) and select lipid parameters....No new safety signals were identified in the Phase 2 study and tolerability was consistent with the GLP-1 class."

P2 data • Obesity • Type 2 Diabetes Mellitus

AMGEN’S PHASE 2 MARITIDE DATA TO BE PRESENTED AT THE AMERICAN DIABETES ASSOCIATION 85TH SCIENTIFIC SESSIONS (PRNewswire) - "Amgen...today announced full results from Part 1 of the Phase 2 study for MariTide (maridebart cafraglutide, formerly AMG 133) in patients living with obesity, with and without Type 2 diabetes, will be presented along with new data from the Phase 3 FOURIER study of Repatha (evolocumab) in cardiovascular disease and the VESALIUS-REAL study of real-world lipid management patterns at the 85th American Diabetes Association (ADA) Scientific Sessions taking place from June 20–23, 2025, in Chicago....The Symposium will highlight 52-week efficacy, safety and tolerability data from Part 1 of the Phase 2 study, complete data from the primary analysis of the Phase 1 pharmacokinetics low dose initiation (PK-LDI) study, and additional information on the Phase 3 MARITIME Chronic Weight Management studies."

P1 data • P2 data • P3 data • Cardiovascular • Dyslipidemia • Obesity