Osmania General Hospital, Hyderabad, India.
G.S.V.M. Medical College, Kanpur, India.
Adv Ther. 2023 Jul;40(7):3227-3246. doi: 10.1007/s12325-023-02523-z. Epub 2023 May 31.
This study compared efficacy and safety of triple drug fixed-dose combination (FDC) of dapagliflozin (DAPA) + sitagliptin (SITA) + metformin (MET) extended release (ER) with SITA + MET sustained release (SR) and DAPA + MET ER in patients with type 2 diabetes poorly controlled with metformin.
This phase 3, randomized, open-label, active-controlled study included adult patients with glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and ≤ 11% (97 mmol/mol), randomized in 1:1:1 ratio to receive either FDC of DAPA + SITA + MET ER (10 mg + 100 mg + 1000 mg) tablets once daily (n = 137) or co-administration of SITA + MET SR (100 mg + 1000 mg) tablets once daily (n = 139) or FDC of DAPA + MET ER (10 mg + 1000 mg) tablets once daily (n = 139). Primary endpoint was mean change in HbA1c from baseline to week 16.
Mean baseline HbA1c was approximately 9% (75 mmol/mol) in each treatment group. At week 16, adjusted mean reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER (- 1.73% [- 19.0 mmol/mol]) compared to SITA + MET SR (- 1.28% [- 14.1 mmol/mol]; difference of - 0.46% [- 5.1 mmol/mol], p < 0.001) and DAPA + MET ER (- 1.33% [- 14.6 mmol/mol]; difference - 0.4% [4.4 mmol/mol], p < 0.001). Similarly, at week 12, reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0006) and DAPA + MET ER (p = 0.0276). At week 16, DAPA + SITA + MET ER showed significant reduction in postprandial blood glucose compared to DAPA + MET ER (p = 0.0394) and significant reduction in fasting blood glucose with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0226). The proportion of patients achieving HbA1c < 7.0% (53 mmol/mol) at week 16 was significantly higher with DAPA + SITA + MET ER (38.5%) versus SITA + MET SR (12.8%) (p < 0.001) and DAPA + MET ER (21.3%) (p = 0.0023). All study medications were well tolerated.
Triple FDC of DAPA + SITA + MET ER tablets once daily was significantly better in achieving glycemic control versus dual combination once daily in patients with type 2 diabetes poorly controlled with metformin without any significant safety concerns.
CTRI/2021/11/038176, registered on 22 November 2021.
本研究比较了每日一次服用达格列净（DAPA）+西他列汀（SITA）+二甲双胍（MET）缓释固定剂量复方（FDC）与每日一次服用 SITA+MET 缓释（SR）和 DAPA+MET 缓释（ER）在二甲双胍控制不佳的 2 型糖尿病患者中的疗效和安全性。
这是一项 3 期、随机、开放标签、阳性对照研究，纳入了糖化血红蛋白（HbA1c）≥8%（64mmol/mol）且≤11%（97mmol/mol）的成年患者，按照 1:1:1 的比例随机分为三组，分别接受 DAPA+SITA+MET ER（10mg+100mg+1000mg）片剂每日一次（n=137）、SITA+MET SR（100mg+1000mg）片剂每日一次（n=139）或 DAPA+MET ER（10mg+1000mg）片剂每日一次（n=139）治疗。主要终点是从基线到第 16 周时 HbA1c 的平均变化。
每组患者的基线 HbA1c 约为 9%（75mmol/mol）。在第 16 周时，与 SITA+MET SR 相比（-1.28%[-14.1mmol/mol]；差值为-0.46%[-5.1mmol/mol]，p<0.001）和 DAPA+MET ER 相比（-1.33%[-14.6mmol/mol]；差值-0.4%[4.4mmol/mol]，p<0.001），DAPA+SITA+MET ER 治疗组的 HbA1c 从基线的平均降低更显著。同样，在第 12 周时，与 SITA+MET SR 相比（p=0.0006）和 DAPA+MET ER 相比（p=0.0276），DAPA+SITA+MET ER 治疗组的 HbA1c 从基线的降低也更显著。在第 16 周时，与 DAPA+MET ER 相比（p=0.0394），DAPA+SITA+MET ER 可显著降低餐后血糖，与 SITA+MET SR 相比（p=0.0226），DAPA+SITA+MET ER 可显著降低空腹血糖。在第 16 周时，与 SITA+MET SR 相比（12.8%）（p<0.001）和 DAPA+MET ER 相比（21.3%）（p=0.0023），DAPA+SITA+MET ER 治疗组达到 HbA1c<7.0%（53mmol/mol）的患者比例显著更高。
所有研究药物均具有良好的耐受性。
与每日一次服用 SITA+MET 联合治疗相比，每日一次服用 DAPA+SITA+MET ER 固定剂量复方在二甲双胍控制不佳的 2 型糖尿病患者中更能有效控制血糖，且无明显安全性问题。
CTRI/2021/11/038176，于 2021 年 11 月 22 日注册。
