Diabetes Dialogue: BELIEVE, GLP-1/GIP Agonists, and CATALYST-2 Results at ADA 2025

Welcome back to Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives!

In this episode of Diabetes Dialogue, cohosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, continue their recap of ADA’s 2025 Scientific Sessions, spotlighting 3 more of the top clinical trials focused on obesity and type 2 diabetes.

They begin with the BELIEVE study, which evaluated bimagrumab, a monoclonal antibody targeting activin type II receptors, in combination with semaglutide. The trial demonstrated that the combination significantly enhanced fat mass reduction while preserving lean mass, compared to either agent alone. Over 48 to 72 weeks, participants receiving combination therapy lost up to 53 pounds, with over 90% of that loss from fat mass. Safety signals were comparable across arms, with muscle spasms, GI symptoms, and acne among the most reported. The hosts underscore the potential of this dual therapy to mitigate the clinically relevant issue of lean mass loss during weight reduction.

Next, Isaacs and Bellini discuss full 52-week results from a phase 2 trial of maritide, a once-monthly GLP-1/GIP receptor agonist. The trial showed up to 20% weight loss despite no clear dose-response relationship, and a weight loss curve that had not yet plateaued. However, GI-related adverse events—particularly nausea and vomiting—were reported in over 75% of participants, with discontinuation rates as high as 29% in non–dose-escalation arms. The speakers suggest slower titration and tailored patient selection could improve tolerability, and they note the upcoming phase 3 trials and ongoing part 2 of the study will further define maritide’s clinical utility.

Isaacs and Bellini also revisit CATALYST-2, a follow-up to the initial study identifying a high prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes. CATALYST-2 evaluated mifepristone, a glucocorticoid receptor antagonist, in patients with confirmed hypercortisolism. At 24 weeks, participants on mifepristone saw a mean A1c reduction of 1.5%, substantial decreases in insulin and sulfonylurea use, and modest weight and waist circumference reductions. Adverse effects were more frequent and included hypokalemia and euglycemic ketoacidosis. The hosts highlight the importance of screening for hypercortisolism in patients with refractory diabetes and hypertension, noting that although the therapy presents tolerability challenges, it represents a paradigm shift in personalized diabetes care.

The episode concludes with a reflection on how emerging therapies—and better phenotyping—are reshaping the approach to obesity, glycemic control, and underlying endocrine drivers of metabolic disease.

Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.