Objective:To evaluate the efficacy and safety of olorigliflozin monotherapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.Methods:The study was a multicenter, randomized, double-blind and placebo-controlled phase Ⅲ clinical trial. A total of 396 T2DM patients with inadequate glycemic control despite diet and exercise were enrolled across 73 research centers nationwide between July 2021 and June 2022. Using a block randomization method stratified by baseline glycated hemoglobin A 1c (HbA 1c) results (≤8.5% and >8.5%) and prior diabetes treatment status, the patients were randomly allocated in a 1∶1∶1 ratio via an interactive response system to the olorigliflozin 20 mg group, 50 mg group, and placebo group. After 24 weeks, the patients in the placebo group were re-randomized in a 1∶1 ratio to the placebo-to-olorigliflozin 20 mg or placebo-to-olorigliflozin 50 mg for an additional 28 weeks using the same randomization method, while the patients in the olorigliflozin groups continued the original treatment. The primary efficacy endpoint was the change in HbA 1c from baseline at week 24, with statistical analysis performed based on the full analysis set (FAS). Secondary efficacy endpoints included: change in HbA 1c from baseline at weeks 52; HbA 1c target achievement rates. The secondary endpoints included the change of from baseline at 52 weeks of treatment, and the HbA 1c compliance rates at 24 weeks and 52 weeks of treatment were analyzed by FAS and FAS-completers(FASc), respectively. Safety set (SS) was used to evaluate the safety of subjects during the whole study period. A mixed-effects model for repeated measures was adopted to assess quantitative efficacy indicators, and descriptive statistics was used for safety evaluation. Results:In FAS, there were 130, 129 and 131 patients in the ololegliflozin 20 mg, 50 mg and placebo groups, respectively; In SS, the corresponding number of patients was 130, 133 and 132, respectively; In FASc, the patient numbers were 123 and 119 in the ololegliflozin 20 mg and 50 mg groups, and 59 and 57 in the placebo-to-ololegliflozin 20 mg and placebo-to-ololegliflozin 50 mg groups, respectively. At week 24, the least squares mean differences (95% CI) in placebo-adjusted changes in HbA 1c from baseline between groups for the olorigliflozin 20 mg group and 50 mg group were -0.94% (-1.14% to -0.74%; P<0.001) and -1.01% (-1.21% to -0.81%; P<0.001), respectively. The proportions of patients with HbA 1c<7% in the placebo group, olorigliflozin 20 mg group and 50 mg group were 20.6% (27/131), 55.4% (72/130) and 56.6% (73/129), respectively; the proportions of patients with HbA 1c≤6.5% were 7.6% (10/131), 31.5% (41/130) and 31.8% (41/129), respectively. At week 52, HbA 1c continued to show decreasing trends. The mean changes from baseline in HbA 1c were -1.33%±0.77%, -1.38%±0.81%, -1.30%±0.69% and -0.90%±0.83%, in the olorigliflozin 20 mg group, olorigliflozin 50 mg group, placebo-to-olorigliflozin 20 mg group, and placebo-to-olorigliflozin 50 mg group, respectively; The proportions of patients with HbA 1c<7% were 59.3% (73/123), 61.3% (73/119), 49.2% (29/59) and 42.1% (24/57) in the four groups, respectively, and the proportions of patients with HbA 1c≤6.5% were 36.6% (45/123), 42.0% (50/119), 33.9% (20/59) and 26.3% (15/57), respectively. Throughout the study period, olorigliflozin demonstrated good safety profile without any episodes of severe hypoglycemia or ketoacidosis. Conclusion:For Chinese patients with T2DM inadequately controlled by diet and exercise, monotherapy with olorigliflozin (20 mg and 50 mg) can effectively control blood glucose, and demonstrate good safety.
(8.0+极速模式)