Korol Sandra, Mottet Fannie, Perreault Sylvie, Baker William L, White Michel, de Denus Simon
Faculty of Pharmacy, Université de Montréal Montreal Heart Institute Faculty of Medicine, Université de Montréal Sanofi Aventis endowment Research Chair in Optimal Drug Use, Université de Montréal, Montreal, Canada School of Pharmacy, University of Connecticut, Storrs, CT, USA.
Medicine (Baltimore). 2017 Dec;96(48):e8719. doi: 10.1097/MD.0000000000008719.
Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs' influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes.
A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, without any restrictions regarding the participants' characteristics.Study design, patient population, dose and duration of intervention, and the quantitative results on glycemic markers were extracted, interpreted for result synthesis, and evaluated for sources of bias. From the articles included in the qualitative analysis, a select number were used in a meta-analysis on studies having measured glycated hemoglobin (HbA1c) or risk of diabetes.
Seventy-two articles were selected from the Medline database and references of articles. Results on spironolactone were heterogeneous, but seemed to be disease-specific. A potential negative effect on glucose regulation was mainly observed in heart failure and diabetes trials, while a neutral or positive effect was detected in diseases characterized by hyperandrogenism, and inconclusive for hypertension. Interpretation of data from heart failure trials was limited by the small number of studies. From a meta-analysis of 12 randomized controlled studies evaluating spironolactone's impact on HbA1c in diabetic patients, spironolactone had a nonsignificant effect in parallel-group studies (mean difference 0.03 [-0.20;0.26]), but significantly increased HbA1c in crossover studies (mean difference 0.24 [0.18;0.31]). Finally, eplerenone did not seem to influence glycemia, while limited data indicated that canrenone may exert a neutral or beneficial effect.The studies had important limitations regarding study design, sample size, duration of follow-up, and choice of glycemic markers.
Spironolactone may induce disease-specific and modest alterations on glycemia. It is uncertain whether these effects are transient or not. Data from the most extensively studied population, individuals with diabetes, do not support a long-term glycemic impact in these patients. Further prospective studies are necessary to establish spironolactone's true biological effects and their clinical implications.
螺内酯，一种非选择性盐皮质激素受体拮抗剂（MRA），可能对血糖产生有害影响。本综述的目的是评估当前关于MRA（螺内酯、依普利酮和坎利酮）对葡萄糖稳态及糖尿病风险影响的知识。
使用Medline数据库对1946年至2017年1月发表的研究MRA对任何与葡萄糖相关终点影响的文章进行系统综述，对参与者特征无任何限制。提取研究设计、患者人群、干预剂量和持续时间以及血糖标志物的定量结果，进行结果综合解释并评估偏倚来源。从定性分析纳入的文章中，选取一部分用于对测量糖化血红蛋白（HbA1c）或糖尿病风险的研究进行荟萃分析。
从Medline数据库及文章参考文献中选取了72篇文章。螺内酯的结果存在异质性，但似乎具有疾病特异性。主要在心力衰竭和糖尿病试验中观察到对葡萄糖调节有潜在负面影响，而在以高雄激素血症为特征的疾病中检测到中性或正面影响，对高血压的影响尚无定论。心力衰竭试验的数据解释因研究数量少而受限。对12项评估螺内酯对糖尿病患者HbA1c影响的随机对照研究进行荟萃分析，螺内酯在平行组研究中无显著影响（平均差异0.03[-0.20;0.26]），但在交叉研究中显著升高HbA1c（平均差异0.24[0.18;0.31]）。最后，依普利酮似乎不影响血糖，而有限的数据表明坎利酮可能产生中性或有益影响。这些研究在研究设计、样本量、随访持续时间和血糖标志物选择方面存在重要局限性。
螺内酯可能对血糖产生疾病特异性且适度的改变。尚不确定这些影响是否短暂。来自研究最广泛的人群（糖尿病患者）的数据不支持对这些患者有长期血糖影响。需要进一步的前瞻性研究来确定螺内酯的真正生物学效应及其临床意义。
