School of Medicine, Wuhan University, No. 115 Donghu Road, Wuhan, 430071, Hubei, China.
Clin Drug Investig. 2019 Jun;39(6):521-531. doi: 10.1007/s40261-019-00781-w.
When metformin is insufficient for patients with type 2 diabetes mellitus (T2DM), the optimal adjunctive therapy is unclear. This meta-analysis was to compare the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors with sulfonylureas (SUs) as second-line therapy in patients with T2DM inadequately controlled on metformin.
We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for randomized controlled trials comparing SGLT2 inhibitors with SUs as add-on to metformin. Our primary endpoints were glycemic control, hypoglycemia, and change in weight. We assessed pooled data using a random-effects model.
Five trials involving 4300 participants were included in our meta-analysis. Compared with SUs, SGLT2 inhibitors led to no significant reduction in changes in HbA1c (mean difference [MD] - 0.06; 95% confidence interval [CI] [- 0.12, 0.08]), but less hypoglycemia as add-on to metformin (odds ratio [OR] 0.12; 95% CI [0.07, 0.21]). SGLT2 inhibitors led to a reduction in weight by about 3.5 kg; however, SUs caused a gain in weight by about 1 kg (MD - 4.39; 95% CI [- 4.64, - 4.14]). SGLT2 inhibitors also showed a reduction in blood pressure, but increased the incidence of genital tract infections compared with SUs. Interestingly, subgroup analysis by duration of interventions showed that reduction of HbA1c from baseline was similar between the two groups at 12-52 weeks, but SGLT2 inhibitors led to a greater reduction in HbA1c at 104-208 weeks.
Despite similar glycemic efficacy in a relatively short term, SGLT2 inhibitors are more effective in the longer term than SUs as add-on to metformin. In addition, SGLT2 inhibitors produce less hypoglycemic events and lead to greater reductions in weight and blood pressure compared with SUs.
当二甲双胍对 2 型糖尿病（T2DM）患者效果不佳时，最佳的辅助治疗方法尚不清楚。本荟萃分析旨在比较钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂与磺酰脲类（SUs）作为二甲双胍控制不佳的 T2DM 患者二线治疗的疗效和安全性。
我们系统地检索了 PubMed、Embase、Cochrane 对照试验中心注册库和 ClinicalTrials.gov，以查找比较 SGLT2 抑制剂与 SUs 作为二甲双胍辅助治疗的随机对照试验。我们的主要终点是血糖控制、低血糖和体重变化。我们使用随机效应模型评估汇总数据。
共有 5 项涉及 4300 名参与者的试验纳入本荟萃分析。与 SUs 相比，SGLT2 抑制剂作为二甲双胍的辅助治疗并未显著降低 HbA1c 变化（平均差值 [MD] -0.06；95%置信区间 [CI] [-0.12, 0.08]），但低血糖发生率较低（比值比 [OR] 0.12；95% CI [0.07, 0.21]）。SGLT2 抑制剂可使体重减轻约 3.5kg；然而，SUs 会使体重增加约 1kg（MD -4.39；95% CI [-4.64, -4.14]）。SGLT2 抑制剂还可降低血压，但与 SUs 相比，增加生殖道感染的发生率。有趣的是，按干预持续时间的亚组分析显示，两组在 12-52 周时从基线的 HbA1c 降低幅度相似，但 SGLT2 抑制剂在 104-208 周时 HbA1c 降低幅度更大。
尽管在相对较短的时间内具有相似的降糖疗效，但 SGLT2 抑制剂作为二甲双胍的辅助治疗在长期效果上优于 SUs。此外，与 SUs 相比，SGLT2 抑制剂发生低血糖事件较少，体重和血压降低幅度更大。
