maridebart cafraglutide (AMG 133) / Amgen - LARVOL DELTA

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

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 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

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

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

MariTide Phase 2 Study—Participants with Obesity (ADA 2025) - No abstract available

P2 data • Metabolic Disorders • Obesity

Potential Impact of MariTide on the Treatment of Obesity and Type 2 Diabetes (ADA 2025) - No abstract available

Diabetes • Metabolic Disorders • Obesity • 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 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Atherosclerosis • Cardiovascular • Genetic Disorders • Obesity

Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. (PubMed, N Engl J Med) - P2 | "In this phase 2 trial, once-monthly maridebart cafraglutide resulted in substantial weight reduction in participants with obesity with or without type 2 diabetes. (Funded by Amgen; ClinicalTrials.gov number, NCT05669599.)."

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

MARITIME-3-J: Efficacy and Safety of Maridebart Cafraglutide in Adult Participants in Japan Who Have Obesity Disease (clinicaltrials.gov) - P3 | N=272 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

MariTide Phase 2 Study—Participants with Obesity and Type 2 Diabetes (ADA 2025) - No abstract available

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

The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs. (PubMed, J Clin Med) - "We focus on the physiologic role of GIP in humans, human genetics evidence, rodent genetic models, and preclinical rodent and non-human primate pharmacology studies. Furthermore, we highlight where early preclinical findings translated into relevant clinical efficacy in the development of tirzepatide and maridebart cafraglutide (MariTide)."

Journal • Review • Genetic Disorders

MARITIME-3-J: Efficacy and Safety of Maridebart Cafraglutide in Adult Participants in Japan Who Have Obesity Disease (clinicaltrials.gov) - P3 | N=272 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Genetic Disorders • Obesity

A Study to Evaluate AMG 133 Administered Subcutaneously in Participants With Overweight or Obesity (clinicaltrials.gov) - P1 | N=120 | Completed | Sponsor: Amgen

New P1 trial • Genetic Disorders • Obesity

A Study of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus (T2DM) (clinicaltrials.gov) - P2 | N=399 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • 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=999 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • 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=3501 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

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

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. (PubMed, Peptides) - "Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)...New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The..."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Nephrology • Obesity • Obstructive Sleep Apnea • Orthopedics • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • 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=3501 | Not yet recruiting | Sponsor: Amgen

New P3 trial • 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=999 | Not yet recruiting | Sponsor: Amgen

New P3 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

AMGEN REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS (PRNewswire) - "MariTide (maridebart cafraglutide, AMG 133): Part 2 of the Phase 2 chronic weight management study is ongoing in adults who are living with overweight or obesity, with or without Type 2 diabetes mellitus. Data readout is anticipated in H2 2025. A Phase 2 study investigating MariTide for the treatment of Type 2 diabetes mellitus is enrolling adults living with and without obesity. Data readout is anticipated in H2 2025. Planning for MARITIME, a broad Phase 3 program across multiple indications remains on track with the first studies expected to begin in H1 2025....AMG 513: A Phase 1 study of AMG 513 in people living with obesity was placed on clinical hold by the U.S. Food and Drug Administration (FDA)."

New P3 trial • P2 data • Trial suspension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice. (PubMed, JCI Insight) - "The clinical development of GIP receptor (GIPR)-GLP-1 receptor (GLP-1R) multi-agonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extra-pancreatic actions of incretin therapies...Here, using gain and loss of function studies, we show that GIP alleviates 5-fluorouracil (5FU)-induced gut inflammation, whereas genetic deletion of Gipr exacerbates the proinflammatory response to 5FU in the murine small bowel (SB)...Within the gut, Gipr was localized to non-immune cells, specifically stromal CD146+ cells. Hence, the extra-pancreatic actions of GIPR signaling extend to the attenuation of gut inflammation, findings with potential translational relevance for clinical strategies modulating GIPR action in people with type 2 diabetes or obesity."

Journal • Preclinical • Diabetes • Endocrine Disorders • Genetic Disorders • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Obesity • Transplantation • Type 2 Diabetes Mellitus • MCAM