AIMS: To provide a clinically oriented narrative review of recently reported human trial data on emerging pharmacotherapies for obesity and type 2 diabetes beyond glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy.
MATERIALS AND METHODS: This narrative review summarizes recent clinical evidence on incretin-based and related therapeutic strategies, including dual and triple incretin- or glucagon-based agonists, long-acting amylin analogues, oral agents, and combination approaches targeting complementary satiety and metabolic pathways. The review focuses on human trial data and evaluates key outcomes including body weight reduction, glycemic control, body-composition effects, tolerability, and broader cardiometabolic changes.
RESULTS: Incretin-based therapies have transformed the management of obesity and type 2 diabetes, with GLP-1RAs achieving levels of weight loss that begin to narrow the gap with metabolic surgery in selected populations. Recent developments have substantially expanded the field beyond GLP-1RA monotherapy. Emerging agents now include multi-agonists, amylin-based therapies, novel oral compounds, and combination strategies designed to improve not only the magnitude of weight loss, but also its quality, durability, and metabolic consequences. Across trials, these approaches have shown promising effects on body weight, glycemic control, and selected cardiometabolic parameters, although differences in tolerability, evidence maturity, and practical feasibility remain important.
CONCLUSIONS: Current data indicate a rapid shift from single-pathway interventions toward multimodal therapeutic strategies in obesity and type 2 diabetes. Future positioning of these agents within treatment algorithms will depend not only on efficacy, but also on long-term safety, durability of effect, tolerability, adherence, access, and their impact on clinically meaningful outcomes beyond body weight alone.
