Efsubaglutide Alfa Trial Reports Glycaemic Benefit With Metformin

Key Takeaways

• Phase 3 HbA1c reduction was greater with efsubaglutide 3 mg than with placebo when added to metformin.
• Phase 2b efficacy and safety findings supported selection of the 3 mg dose for phase 3.
• Adverse events were reported as mainly mild to moderate gastrointestinal events.

Phase 3 data showed that efsubaglutide alfa added to metformin lowered HbA1c by 1.80% at week 24, compared with 0.74% for placebo in adults with type 2 diabetes. The estimated treatment difference was −1.06%, with a statistically significant between-group difference (p < 0.001). Efsubaglutide alfa was evaluated as a long-acting humanised GLP-1 receptor agonist added to metformin, and phase 3 evaluated the selected 3 mg dose in a larger placebo-controlled cohort within the trial’s two-stage development program.

Investigators evaluated efsubaglutide alfa as add-on therapy to metformin in adults with type 2 diabetes in an operationally seamless adaptive phase 2b/3, randomized, double-blind, placebo-controlled study. The design combined dose finding with a later placebo-controlled comparison while maintaining blinding and placebo control across both stages. In phase 2b, participants were assigned in a 1:1:1 ratio to efsubaglutide 1 mg, efsubaglutide 3 mg, or placebo for 12 weeks. An independent committee then selected 3 mg as the recommended phase 3 dose on the basis of phase 2b efficacy and safety. Phase 3 randomized new participants 1:1 to efsubaglutide 3 mg or placebo for 24 weeks of double-blind treatment, followed by a 28-week open-label extension.

HbA1c reductions were evident in phase 2b after 12 weeks of blinded treatment. HbA1c fell by 1.10% with efsubaglutide 1 mg and by 1.43% with efsubaglutide 3 mg at week 12, with both results reported at p < 0.0001. The larger reduction at 3 mg aligned with the dose selected for phase 3 evaluation. Together with the safety review, those dose-finding results informed the committee’s decision to advance the 3 mg dose into the larger placebo-controlled comparison. Phase 3 findings were consistent with the earlier dose-selection stage, with continued HbA1c lowering observed in the later placebo-controlled analysis. Adverse events were described as predominantly mild to moderate gastrointestinal events.