733-P: Efficacy and Safety of HS-20094 in Patients with Type 2 Diabetes—A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

Introduction and Objective: HS-20094 is a novel dual GIP and GLP-1 receptor agonist. A 4-week POC study was conducted to assess the preliminary efficacy and safety of HS-20094 in patients with type 2 diabetes (T2DM).

Methods: This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov number, NCT06118008). Patients with T2DM poorly controlled with diet and exercise alone or with stable metformin (HbA_1c ≥7.0 to ≤10.0%) were randomly (4:1:1) assigned within each cohort to receive HS-20094 (5mg, 10mg or 15mg), semaglutide (1.0mg), or placebo subcutaneously once-weekly. The primary outcome was the change in HbA_1c from baseline to week 4. Efficacy results between groups were compared using analysis of covariance (ANCOVA) with baseline value as a covariate and status of metformin use as a fixed effect.

Results: Totally, 54 subjects received at least one dose of HS-20094, semaglutide or placebo. Least square mean (LSM) change in HbA_1c was -0.63%, -0.75%, -0.84%, and -0.59% in HS-20094 of 5mg, 10mg, 15mg and semaglutide, respectively (all p<0.01 vs placebo). LSM change in fasting blood glucose in corresponding cohort was -2.87, -2.25, -2.79, and -1.92mmol/L, respectively (all p<0.01 vs placebo). LSM percent change in body weight was -1.27%, -2.51%, -4.41%, and -1.35%, respectively (p = 0.192, p= 0.016, p<0.001, and p = 0.179 vs placebo). The occurrence of adverse events (AEs) was not dose-dependent in HS-20094. The most common AE included decreased appetite, abdominal distension and vomiting. No severe hypoglycemia was reported.

Conclusion: In patients with T2DM, HS-20094 was generally safe and showed meaningful HbA_1c, fasting blood glucose and body weight reductions.