Advances in incretin-based drug discovery in 2025

The efficacy of anti-obesity drugs that use glucagon-like peptide 1 receptor agonism and glucose-dependent insulinotropic polypeptide agonism raises critical questions about how next-generation drugs might offer increased metabolic benefits. In 2025, new research into incretin-based treatments has brought us closer to answering these questions.

Key advances

• In a head-to-head comparison, 10–15 mg tirzepatide produces greater weight loss than 2.4 mg semaglutide in individuals with obesity who do not have type 2 diabetes mellitus⁵.

• In a head-to-head comparison, 7.2 mg semaglutide achieves 3.1% greater weight loss relative to 2.4 mg semaglutide in people with obesity without type 2 diabetes mellitus, albeit at the cost of slightly higher incidences of gastrointestinal adverse effects¹.

• CagriSema yields body weight reduction similar to that previously observed with tirzepatide, albeit with somewhat higher rates of gastric discomfort².

• MariTide induces double-digit weight loss in individuals with obesity who do not have diabetes mellitus, but the high frequency of gastrointestinal adverse effects warrants further investigation in larger trials³.

• Orforglipron seems to induce less weight loss than injectable, peptide-based anti-obesity medications but, given its small-molecule oral formulation and the observation that a substantial number of patients achieve >10% weight loss⁴, represents a cost-efficient alternative to injectable anti-obesity medications.