Ado Moumouni Abdel Nasser, Robin Perrine, Hillaire-Buys Dominique, Faillie Jean-Luc
Department of Medical Pharmacology and Toxicology, CHU Montpellier University Hospital, Montpellier, 34295, France.
INSERM U1058, Faculty of Medicine, University of Montpellier, Montpellier, 34394, France.
Fundam Clin Pharmacol. 2018 Apr;32(2):216-226. doi: 10.1111/fcp.12334. Epub 2017 Nov 29.
SGLT-2 inhibitors, also called gliflozins, are a new class of drugs used in type 2 diabetes. Since their marketing, several cases of ketoacidosis, including life-threatening conditions, were reported with their use. The objective of this study was to investigate the disproportionality of pharmacovigilance reports of ketoacidosis between gliflozins and other drugs used for type 2 diabetes. We performed a case-noncase study within the World Health Organization's pharmacovigilance database, VigiBase. We selected all reports of serious adverse drug reaction associated with a glucose-lowering drug in patients aged 40 years and older, from January 2013 to March 2016. Cases were the reports of ketoacidosis and noncases were all other serious adverse drug reactions reported. We studied the disproportionality of reports of ketoacidosis for gliflozins by calculating reporting odds ratios (ROR) with their 95% confidence interval (95% CI). We also measured the disproportionality before the warnings issued by the US and European medicines agencies. A total of 68 555 notifications were selected. We identified 487 cases of ketoacidosis exposed to gliflozins. Ketoacidosis was significantly more frequently reported with gliflozins than with other glucose-lowering drugs (adjusted ROR 15.5; 95% CI: 12.8-18.7). The disproportionality of gliflozin reports was also found before the alerts of the medicines agencies. Our study shows a significant and early pharmacovigilance signal which suggests an increased risk of ketoacidosis associated with the use of gliflozins in patients with diabetes. Further studies are needed to confirm this potential risk.
钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂，也称为格列净类药物，是用于2型糖尿病治疗的一类新型药物。自其上市以来，有报道称使用该类药物出现了几例酮症酸中毒病例，包括危及生命的情况。本研究的目的是调查格列净类药物与其他用于2型糖尿病的药物相比，酮症酸中毒药物警戒报告的不成比例性。我们在世界卫生组织的药物警戒数据库VigiBase中进行了一项病例-非病例研究。我们选取了2013年1月至2016年3月期间40岁及以上患者中与降糖药物相关的所有严重药品不良反应报告。病例为酮症酸中毒报告，非病例为报告的所有其他严重药品不良反应。我们通过计算报告比值比（ROR）及其95%置信区间（95%CI）来研究格列净类药物酮症酸中毒报告的不成比例性。我们还在美欧药品监管机构发布警告之前测量了不成比例性。总共选取了68555份通知。我们确定了487例暴露于格列净类药物的酮症酸中毒病例。与其他降糖药物相比，格列净类药物报告的酮症酸中毒明显更频繁（校正ROR为15.5；95%CI：12.8 - 18.7）。在药品监管机构发出警示之前，也发现了格列净类药物报告的不成比例性。我们的研究显示了一个显著且早期的药物警戒信号，提示糖尿病患者使用格列净类药物会增加酮症酸中毒风险。需要进一步研究来证实这一潜在风险。
