Team Pharmacoepidemiology, Bordeaux Population Health Research Center, Inserm U1219, Univ. Bordeaux, 33000, Bordeaux, France.
Centre Régional de Pharmacovigilance et d'Information sur le Médicament de Bordeaux, Service de Pharmacologie Médicale, Pôle de Santé Publique, CHU Bordeaux, 33000, Bordeaux, France.
Drug Saf. 2020 Aug;43(8):767-774. doi: 10.1007/s40264-020-00936-1.
After a safety warning was issued for a risk of muscular injury associated with dipeptidyl peptidase-4 (DPP-4) inhibitor use, especially when co-prescribed with statins, spontaneous reporting analyses provided conflicting results.
The aim of this study was to investigate the association between DPP-4 inhibitor use and the risk of muscular injury in individuals with type 2 diabetes mellitus using statins or fibrates.
We conducted a nested case-control study amongst a cohort of individuals with type 2 diabetes using statins or fibrates, identified from a nationwide French health insurance database (2009-2014). Cases of serious muscular injury were defined as subjects hospitalized for rhabdomyolysis or myopathy, or for whom testing for myoglobin or creatine phosphokinase followed by a change in statin or fibrate prescription (dose decrease, treatment switch, or stop) was identified. Up to ten controls were matched to each case according to sex, age, and type of lipid-lowering agent. Associations between DPP-4 inhibitor use and serious muscular injury were estimated using a multivariate conditional logistic regression model, providing odds ratios (ORs) adjusted for alcoholism, chronic renal failure, hypothyroidism, and number of concomitant drugs.
Within the 35,117 individuals with type 2 diabetes mellitus constituting the source cohort, 437 statin-user cases were identified who were matched to 4358 statin-user controls. Similarly, 54 fibrate-user cases were identified who were matched to 540 fibrate-user controls. The adjusted OR for DPP-4 inhibitor use and serious muscular injury was estimated at 1.0 (95% confidence interval [CI] 0.7-1.2) in statin users and 0.8 (95% CI 0.4-1.9) in fibrate users.
In this study, DPP-4 inhibitor use was not associated with an increased risk of serious muscular injury among patients with type 2 diabetes mellitus using statins or fibrates.
在发出与二肽基肽酶-4（DPP-4）抑制剂使用相关的肌肉损伤风险的安全性警告后，特别是当与他汀类药物联合使用时，自发报告分析得出了相互矛盾的结果。
本研究旨在调查在使用他汀类药物或贝特类药物的 2 型糖尿病患者中，DPP-4 抑制剂的使用与肌肉损伤风险之间的关系。
我们在法国全国性健康保险数据库（2009-2014 年）中进行了一项嵌套病例对照研究，该研究纳入了使用他汀类药物或贝特类药物的 2 型糖尿病患者队列。严重肌肉损伤的病例定义为因横纹肌溶解症或肌病住院治疗的患者，或因肌红蛋白或肌酸磷酸激酶检测后他汀类药物或贝特类药物处方（剂量减少、药物转换或停药）改变而确定的患者。根据性别、年龄和降脂药物类型，每个病例匹配了最多 10 个对照。使用多变量条件逻辑回归模型估计 DPP-4 抑制剂使用与严重肌肉损伤之间的关联，并调整了酒精中毒、慢性肾衰竭、甲状腺功能减退和同时使用药物数量的比值比（OR）。
在构成源队列的 35117 名 2 型糖尿病患者中，确定了 437 名使用他汀类药物的患者作为病例，与 4358 名使用他汀类药物的对照相匹配。同样，确定了 54 名使用贝特类药物的患者作为病例，与 540 名使用贝特类药物的对照相匹配。在他汀类药物使用者中，DPP-4 抑制剂使用与严重肌肉损伤的调整 OR 估计为 1.0（95%置信区间 [CI] 0.7-1.2），在贝特类药物使用者中为 0.8（95% CI 0.4-1.9）。
在这项研究中，在使用他汀类药物或贝特类药物的 2 型糖尿病患者中，DPP-4 抑制剂的使用与严重肌肉损伤风险增加无关。
