Exploring New Horizons in Incretin Therapy for Diabetes and Weight Loss

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In this episode, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector 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, explore recent advancements in incretin-based therapies, highlighting their transformative potential for diabetes management and weight loss.

The episode opens with a detailed discussion on Amgen’s maridebart cafraglutide (MariTide; AMG-133), an investigational antibody peptide conjugate offering remarkable efficacy for obesity and overweight in Phase 2 trial data. At 52 weeks, participants without type 2 diabetes (T2D) experienced an average weight loss of ~20% with MariTide treatment without a weight loss plateau, while those with T2D achieved up to a ~17% average reduction without a plateau. The hosts underscored the potential impact of this type of therapy, particularly in addressing adherence challenges posed by the more frequent dosing schedules of current options. Hosts cited the potential safety concerns, but noted that AMG-133 could represent a significant step forward in managing obesity and related metabolic disorders.

The conversation then shifted to a head-to-head comparison of two leading incretin therapies for obesity: tirzepatide (Zepbound) and semaglutide (Wegovy). Tirzepatide emerged as a frontrunner in the SURMOUNT-5 trial, contributing to a mean body weight reduction of 20.2% versus 13.7% achieved with semaglutide. Isaacs and Bellini discuss how these findings might influence clinical decision-making, emphasizing the importance of tailoring treatment plans to individual patient needs. They also touch on the practical implications of these therapies in both obesity and diabetes care, given the growing prevalence of these conditions.

In the final segment, Isaacs and Bellini addressed a critical safety issue: the proliferation of non-FDA-approved compounded glucgaon-like peptide-1 (GLP-1) receptor agonists. The American Diabetes Association (ADA) released a statement warning against these unregulated formulations due to concerns over safety, quality control, and potential adverse effects. Despite the growing popularity of compounded versions as a lower-cost alternative, the hosts stressed the importance of prioritizing patient safety. They advised clinicians to steer patients toward evidence-based, FDA-approved therapies that have undergone rigorous testing and demonstrated consistent efficacy and safety profiles.

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.