Diabetology, Careggi Hospital and University of Florence, Italy.
Cardiothoracovascular Department, Careggi Hospital and University of Florence, Italy.
Diabetes Res Clin Pract. 2019 Jul;153:138-144. doi: 10.1016/j.diabres.2019.05.028. Epub 2019 May 28.
Concerns have been raised on the risk of lower limb amputations with SGLT-2 inhibitors. Aim of the present metanalysis is the assessment of the effect of SGLT-2inhibitors on peripheral artery disease and lower limb amputations in randomized controlled trials performed in patients with type 2 diabetes.
A Medline and Embase search for "Canaglifozin" OR "Dapaglifozin" OR "Empaglifozin" OR "Ertuglifozin" OR "Ipraglifozin" OR Tofoglifozin" OR "Luseoglifozin" was performed, collecting randomized clinical trials (duration > 12 weeks) up to December 1st, 2018, comparing SGLT-2i at approved dose with placebo or other active comparators different from SGLT-2 inhibitors. Furthermore, unpublished studies were searched in the www.clinicaltrials.gov register. Separate analyses were performed for individual molecules of the class. In addition, a separate analysis was performed for placebo-controlled trials. Mantel-Haenszel odds ratio with 95% Confidence Interval (MH-OR) was calculated for all outcomes defined above.
A total of 27 trials fulfilling the inclusion criteria was identified. The overall incidence of peripheral artery disease was increased with SGLT-2 inhibitors (MH-OR: 1.26 [1.04, 1.52]). The increase of risk was statistically significant only with canagliflozin. MH-OR for amputation in the three cardiovascular safety trials with SGLT-2 inhibitors was 1.22 [0.59-2.52].
At present, there is no reason to believe that empagliflozin or dapagliflozin increase the risk of either peripheral artery disease of lower limb amputations. Canagliflozin could be associated with a specific risk, which needs to be further investigated.
人们对 SGLT-2 抑制剂导致下肢截肢的风险表示担忧。本荟萃分析的目的是评估 SGLT-2 抑制剂在 2 型糖尿病患者中进行的随机对照试验对周围动脉疾病和下肢截肢的影响。
对 Medline 和 Embase 进行了“Canagliflozin”或“Dapagliflozin”或“Empagliflozin”或“Ertuglifozin”或“Ipraglifozin”或“Tofoglifozin”或“Luseoglifozin”的搜索，收集截至 2018 年 12 月 1 日的、比较 SGLT-2i 与安慰剂或其他与 SGLT-2 抑制剂不同的活性对照药物的持续时间超过 12 周的随机临床试验。此外，还在 www.clinicaltrials.gov 登记处搜索了未发表的研究。对该类别的各个分子进行了单独分析。此外，还对安慰剂对照试验进行了单独分析。对上述所有定义的结局均采用 Mantel-Haenszel 比值比（MH-OR）和 95%置信区间（MH-OR）进行计算。
共确定了 27 项符合纳入标准的试验。SGLT-2 抑制剂可增加外周动脉疾病的总体发生率（MH-OR：1.26 [1.04，1.52]）。这种风险增加仅在坎格列净中具有统计学意义。在有 SGLT-2 抑制剂的 3 项心血管安全性试验中，截肢的 MH-OR 为 1.22 [0.59-2.52]。
目前，没有理由认为恩格列净或达格列净会增加外周动脉疾病或下肢截肢的风险。卡格列净可能与特定风险相关，需要进一步研究。
