Division of diabetes, nutrition and metabolic disorders, department of medicine, CHU Liège, Liège University, Liège, Belgium; Clinical pharmacology unit, Centre for interdisciplinary research on medicines (CIRM), CHU Liège, Liège University, Liège, Belgium.
Diabetes Metab. 2020 Jun;46(3):186-196. doi: 10.1016/j.diabet.2020.01.002. Epub 2020 Jan 30.
This study compared the reduction of glycated haemoglobin (HbA1c) with sodium-glucose cotransporter type-2 inhibitors (SGLT2is) vs. dipeptidyl peptidase-4 inhibitors (DPP-4is) as add-ons to metformin in patients with type 2 diabetes mellitus (T2DM), with a specific focus on HbA1c changes according to baseline HbA1c.
Electronic databases were scrutinized for randomized controlled trials (RCTs) evaluating the reduction of HbA1c from baseline (Δ HbA1c) with an SGLT2i or DPP-4i in patients with T2DM not well controlled by metformin monotherapy. The endpoint was Δ HbA1c using both indirect and direct comparisons.
Overall, Δ HbA1c was slightly greater with SGLT2is (-0.80±0.20% from 8.03±0.35%; 44 analyses, 29 RCTs, 15 with two doses, n=9321) than with DPP-4is (-0.71±0.23% from 8.05±0.43%; 61 analyses, 59 RCTs, n=17,914; P=0.0354). When the mean baseline HbA1c was<8% ([64mmol/mol] 7.79±0.15% vs. 7.71±0.23%), Δ HbA1c averaged -0.735±0.17% vs. -0.62±0.16% (P=0.0117) with SGLT2is vs. DPP-4is, respectively. However, this difference vanished when the mean baseline HbA1c was≥8% (-0.87±0.22% from 8.27±0.32% with SGLT2is vs. -0.80±0.24% from 8.35±0.33% with DPP-4is; P=0.2756). The relationship between Δ HbA1c and baseline HbA1c was only slightly stronger with SGLT2is (slope: -0.39, r=-0.43; P<0.0001) than with DPP-4is (slope: -0.26, r=-0.25; P<0.0001).
Because of the small difference in Δ HbA1c whatever the baseline HbA1c level with SGLT2is vs. DPP-4is as add-ons to metformin, choosing between these glucose-lowering agents in clinical practice should be based on other efficacy criteria (such as weight and blood pressure changes, cardiovascular and renal protection) or on safety profiles rather than on HbA1c levels.
本研究比较了钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）与二肽基肽酶-4 抑制剂（DPP-4i）作为附加药物联合二甲双胍治疗 2 型糖尿病（T2DM）患者糖化血红蛋白（HbA1c）降低的效果，特别关注根据基线 HbA1c 水平观察 HbA1c 的变化。
检索电子数据库，评估 SGLT2i 或 DPP-4i 与二甲双胍单药治疗效果不佳的 T2DM 患者基线 HbA1c 降低的随机对照试验（RCT）。终点为间接和直接比较的 HbA1c 差值。
总体而言，SGLT2i 降低 HbA1c 的幅度略高于 DPP-4i（从 8.03±0.35%降至 7.30±0.20%，44 项分析，29 项 RCT，15 项使用两种剂量，n=9321）（-0.71±0.23%，从 8.05±0.43%降至 7.32±0.23%，61 项分析，59 项 RCT，n=17914；P=0.0354）。当平均基线 HbA1c<8%（[64mmol/mol]7.79±0.15% vs. 7.71±0.23%）时，SGLT2i 组和 DPP-4i 组的 HbA1c 差值平均为-0.735±0.17% vs. -0.62±0.16%（P=0.0117）。然而，当平均基线 HbA1c≥8%时，这种差异消失（SGLT2i 组从 8.27±0.32%降至 8.07±0.22%，DPP-4i 组从 8.35±0.33%降至 8.00±0.24%；P=0.2756）。SGLT2i 组与 DPP-4i 组的 HbA1c 差值与基线 HbA1c 之间的关系仅略强于 SGLT2i 组（斜率：-0.39，r=-0.43；P<0.0001）。
由于 SGLT2i 与 DPP-4i 联合二甲双胍治疗患者的 HbA1c 差值无论基线 HbA1c 水平如何都很小，因此在临床实践中选择这些降糖药物应基于其他疗效标准（如体重和血压变化、心血管和肾脏保护）或安全性特征，而不是 HbA1c 水平。
