Monami Matteo, Nreu Besmir, Zannoni Stefania, Lualdi Carlotta, Mannucci Edoardo
Diabetology, University of Florence and Careggi Teaching Hospital, Florence, Italy.
Geriatric Medicine, University of Florence and Careggi Teaching Hospital, Florence, Italy.
Diabetes Res Clin Pract. 2017 Aug;130:53-60. doi: 10.1016/j.diabres.2017.04.017. Epub 2017 May 18.
Diabetic ketoacidosis (DKA) associated with SGLT-2 inhibitors (SGLT-2i) is a possible adverse event. In fact, SGLT-2i are capable of stimulating the release of glucagon and ketone re-absorption in the renal tubuli, thus increasing the concentration of ketone bodies.
A Medline search for SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials with a duration of treatment≥12weeks, enrolling patients with type 2 diabetes, and comparing a SGLT2i with placebo or other comparators. The principal outcome was the effect of SGLT2i on ketoacidosis as serious adverse event.
Out of 72 trials reporting information on DKA, 9 reported at least one event of ketoacidosis; those eight trials enrolled 10,157 and 5396 in SGLT-2 inhibitors and comparator groups, respectively. No signal of increased risk for ketoacidosis was observed for SGLT2 inhibitors as a class (MH-OR [95% CI] 1.14 [0.45-2.88], p=0.78) or as individual molecule. The sensitivity analysis with continuity correction (inputing one event each in drug and comparator arms of each trial with zero events) suggested a reduced incidence of ketoacidosis in patients treated with SGLT-2 inhibitors (MH-OR 0.65 [0.47-0.90]; p=0.01).
The results of clinical trials summarized in the present meta-analysis reassure us that, when the drug is properly prescribed, the risk of DKA is negligible.
与钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）相关的糖尿病酮症酸中毒（DKA）是一种可能的不良事件。事实上，SGLT-2i能够刺激胰高血糖素的释放以及肾小管中酮体的重吸收，从而增加酮体浓度。
对SGLT2i（达格列净、恩格列净、卡格列净、依帕列净、艾托格列净、鲁格列净）进行了医学文献检索，收集了所有治疗持续时间≥12周、纳入2型糖尿病患者且将SGLT2i与安慰剂或其他对照药物进行比较的随机试验。主要结局是SGLT2i对作为严重不良事件的酮症酸中毒的影响。
在72项报告DKA信息的试验中，9项报告了至少1例酮症酸中毒事件；这8项试验中，SGLT-2抑制剂组和对照组分别纳入了10157例和5396例患者。未观察到SGLT2抑制剂作为一个类别（Mantel-Haenszel比值比[95%置信区间]1.14[0.45-2.88]，p=0.78）或作为单个分子有酮症酸中毒风险增加的信号。采用连续性校正的敏感性分析（在每个事件数为零的试验的药物组和对照组各输入1个事件）表明，接受SGLT-2抑制剂治疗的患者酮症酸中毒发生率降低（Mantel-Haenszel比值比0.65[0.47-0.90]；p=0.01）。
本荟萃分析总结的临床试验结果让我们放心，当药物合理处方时，DKA的风险可以忽略不计。
