Steno Diabetes Center Copenhagen, University of Copenhagen, Copenhagen, Denmark
AstraZeneca Gothenburg, Mölndal, Sweden.
Diabetes Care. 2019 Aug;42(8):1464-1472. doi: 10.2337/dc18-1988. Epub 2019 Jun 4.
This study evaluated whether an oral combination of a sodium-glucose cotransporter 2 inhibitor and a dipeptidyl peptidase 4 inhibitor achieved glycemic control similar to basal insulin in patients with type 2 diabetes, poorly controlled with metformin, without increasing hypoglycemia or body weight.
In a multinational, open-label, randomized, phase 3 trial (ClinicalTrials.gov reg. no. NCT02551874), adults with type 2 diabetes inadequately controlled on metformin, with or without sulfonylurea, were randomized (1:1) to receive dapagliflozin (DAPA) plus saxagliptin (SAXA) or titrated insulin glargine (INS). The primary end point was change in glycated hemoglobin A (HbA) from baseline to week 24. DAPA + SAXA treatment was tested for noninferiority versus INS.
The efficacy data set included 643 patients (mean ± SD HbA, 9.1 ± 1.0% [75 ± 11 mmol/mol]). At week 24, DAPA + SAXA treatment versus INS resulted in noninferior reductions in HbA (adjusted mean ± SE change, -1.7 ± 0.1% vs. -1.5 ± 0.1% [18.3 ± 0.7 mmol/mol vs. 16.8 ± 0.7 mmol/mol]; = 0.118), significantly different body weight change (between-group difference, -3.64 kg [95% CI -4.20 to -3.09]; < 0.001), fewer patients with confirmed hypoglycemia (21.3% vs. 38.4%, < 0.001), more patients achieving HbA <7.0% (53 mmol/mol) without hypoglycemia (20.9% vs. 13.1%, = 0.008), and a similar proportion of patients achieving HbA <7.0% (33.2% vs. 33.5%, = 0.924). Mean reductions in 24-h glucose measurements from baseline to week 2 were greater with DAPA + SAXA than with INS ( < 0.0001). No patients in the DAPA + SAXA group and three patients (0.9%) in the INS group experienced severe hypoglycemia.
Adding DAPA + SAXA to insulin-naive patients with poorly controlled type 2 diabetes achieved similar glycemic control, a lower risk of hypoglycemia, and a clinically relevant body weight difference compared with basal INS.
本研究旨在评估钠-葡萄糖共转运蛋白 2 抑制剂与二肽基肽酶 4 抑制剂联合口服治疗，是否可在二甲双胍控制不佳的 2 型糖尿病患者中实现与基础胰岛素相似的血糖控制效果，同时不增加低血糖或体重。
在一项多中心、开放性、随机、3 期临床试验（ClinicalTrials.gov 注册号：NCT02551874）中，血糖控制仍不佳的二甲双胍单药治疗、或联合磺酰脲类药物治疗的 2 型糖尿病成人患者，按 1:1 随机分组，分别接受达格列净（DAPA）+沙格列汀（SAXA）或甘精胰岛素滴定治疗。主要终点为自基线至 24 周时糖化血红蛋白 A1c（HbA）的变化。DAPA+SAXA 治疗与胰岛素的非劣效性进行了检验。
纳入 643 例患者（平均±标准差 HbA，9.1±1.0%[75±11mmol/mol]）进入疗效数据集。至 24 周时，与胰岛素相比，DAPA+SAXA 治疗可使 HbA 显著降低（调整后平均±SE 变化值，-1.7±0.1% vs.-1.5±0.1%[18.3±0.7mmol/mol vs.16.8±0.7mmol/mol]； =0.118），体重减轻差异具有统计学意义（两组间差值，-3.64kg[95%CI-4.20 至-3.09]；<0.001），低血糖确认发生率更低（21.3% vs.38.4%，<0.001），更多患者实现 HbA<7.0%（无低血糖，53mmol/mol）而无需低血糖治疗（20.9% vs.13.1%， =0.008），且 HbA<7.0%（33.2% vs.33.5%， =0.924）的患者比例相似。自基线至 24 周时，24 小时葡萄糖测量值的平均降幅 DAPA+SAXA 组大于胰岛素组（<0.0001）。DAPA+SAXA 组无患者发生严重低血糖，胰岛素组有 3 例（0.9%）发生严重低血糖。
与基础胰岛素相比，在新诊断为 2 型糖尿病且血糖控制不佳的患者中，加用 DAPA+SAXA 可实现相似的血糖控制，低血糖风险更低，且体重减轻具有临床意义。
