Department of Pharmacy, Aerospace Center Hospital, Beijing, China.
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
Front Endocrinol (Lausanne). 2023 Aug 28;14:1238399. doi: 10.3389/fendo.2023.1238399. eCollection 2023.
The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.
This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.
Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.
In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety.
https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
由于缺乏头对头比较，不同的钠-葡萄糖共转运蛋白 2（SGLT-2）抑制剂的安全性仍不确定。
本网络荟萃分析（NMA）旨在比较 9 种 SGLT-2 抑制剂在 2 型糖尿病（T2DM）患者中的安全性。检索了 2022 年 8 月 30 日前发表在英文期刊上的 PubMed、Embase、Cochrane 对照试验中心注册库和 ClinicalTrials.gov 中的研究。纳入了比较 T2DM 患者中单独使用 SGLT-2 抑制剂安全性的已发表和未发表的随机对照试验（RCT）。采用随机效应模型的贝叶斯 NMA。进行了亚组和敏感性分析。使用网络荟萃分析置信度框架评估证据质量。
在 113 项 RCT（12 项注册研究）中评估了 9 种 SGLT-2 抑制剂，共纳入了 105293 名成年患者。SGLT-2 抑制剂组和安慰剂组分别有 1967（4.51%）和 276（1.01%）例患者发生生殖道感染（RTI）。此外，分别有 233（2.66%）和 45（0.84%）例患者出现尿频。与安慰剂相比，卡格列净、埃格列净、恩格列净、瑞格列净、达格列净和索格列净可显著增加 RTI 的风险，但鲁格列净和伊格列净则不会，且无论性别如何。达格列净（OR 10.40，95%CI 1.60-157.94）和恩格列净（OR 5.81，95%CI 1.79-32.97）可增加尿频的风险。瑞格列净（OR 6.45，95%CI 2.18-27.79）和达格列净（OR 1.33，95%CI 1.10-1.62）与尿路感染（UTI）风险增加相关。相反，纳入的 SGLT-2 抑制剂对急性肾损伤（AKI）具有保护作用。SGLT-2 抑制剂组与安慰剂组在血容量减少、肾功能不全或衰竭、骨折、糖尿病酮症酸中毒（DKA）、截肢和严重低血糖症方面无显著差异。
在 T2DM 患者中，达格列净与 RTI、尿频和 UTI 的风险增加相关。恩格列净增加了 RTI 和尿频的风险。瑞格列净增加了 UTI 的风险。与安慰剂相比，没有一种 SGLT-2 抑制剂在血容量减少、肾功能不全或衰竭、骨折、DKA、截肢和严重低血糖症方面有显著差异。这些发现指导了根据患者特征选择 SGLT-2 抑制剂用于 T2DM 患者，以最大限度地提高安全性。
https://www.crd.york.ac.uk/prospero，标识符 CRD42022334644。
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