HSK7653, a Novel Ultralong-Acting DPP-4 Inhibitor, as Monotherapy in Patients With Type 2 Diabetes-A Randomized, Double-Blind, Placebo-Controlled Phase III Trial

Background: HSK7653 is a novel ultralong-acting DPP-4 inhibitor that maintains the average plasma DPP-4 inhibition over 80% for 14 days after 10mg or 25mg dosing. This randomized, double-blind, placebo-controlled phase III trial was conducted to evaluate the efficacy and safety of HSK7653 biweekly as monotherapy for 52 weeks in drug naive type 2 diabetes patients with inadequate glycemic control on diet and exercise. Methods: A total of 475 patients with a mean HbA1c level of 8.1% were randomized to HSK7653 10mg, 25mg or placebo biweekly at a ratio of 1:1:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label extension treatment with HSK7653 25mg for all patients. The primary endpoint was the change in HbA1c from baseline at 24 weeks. Results: At week 24, the least-squares mean change in HbA1c from baseline was -0.96% in HSK7653 10mg, -0.92% in HSK7653 25mg and -0.33% in placebo. HSK7653 10mg and 25mg treatment resulted in significant placebo-subtracted changes in HbA1c of -0.63% (95% CI: -0.81%, -0.46%, p<0.0001) and -0.59% (95% CI: -0.77%, -0.42%, p<0.0001), respectively. The percentage of patients achieving HbA1c<7.0% was 44.2% in HSK7653 10mg group and 44.4% in HSK7653 25mg group versus 20.6% in placebo group (p<0.0001 for HSK7653 groups vs. placebo). No meaningful body weight changes were observed in all treatment groups. In the open-label extension treatment (from week 24 to week 52), the sustaining reduction of HbA1c from baseline were observed in HSK7653 10mg switched to 25mg group and HSK7653 25mg maintenance group. There were no excess hypoglycemia events in HSK7653 vs. placebo, and the incidence of adverse events was similar in all groups during the treatment. Conclusions: In people with type 2 diabetes who had inadequate glycemic control on diet and exercise, HSK7653 monotherapy significantly improved glycemic control with well tolerability and safety. Clinical trial information: NCT04556851. Disclosure L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. F.Bian: None. T.Pan: None. H.Jiang: None. C.Jiang: None. Q.Ren: None.