Efsubaglutide alfa added to metformin improves glycaemia with β-cell functional responses in type 2 diabetes: a randomised, double-blind, placebo-controlled, two-stage adaptive phase 2b/3 trial (SUPER 2)

Efsubaglutide alfa, a long-acting humanised GLP-1 receptor agonist, was evaluated as add-on therapy to metformin in adults with type 2 diabetes. In an operationally seamless adaptive phase 2b/3, randomised, double-blind, placebo-controlled trial, phase 2b randomised participants 1:1:1 to Efsubaglutide 1 mg, 3 mg, or placebo for 12 weeks; based on phase 2b efficacy and safety, an independent committee selected 3 mg as the recommended phase 3 dose. Phase 3 randomised new participants 1:1 to Efsubaglutide 3 mg or placebo for 24-week double-blind treatment, followed by a 28-week open-label extension. At week 12 in phase 2b, HbA1c decreased by 1.10% with 1 mg and 1.43% with 3 mg (both p < 0.0001). At week 24 in phase 3, HbA1c decreased by 1.80% with Efsubaglutide 3 mg versus 0.74% with placebo (estimated treatment difference, -1.06%; p < 0.001). Adverse events were predominantly mild to moderate gastrointestinal events. Trial registration: ClinicalTrials.gov NCT04998032.