Since the introduction of DPP-4 inhibitors, vildagliptin has accumulated extensive efficacy/effectiveness and safety data from various meta-analyses of clinical trials, large randomized controlled trials, non-interventional studies, and post-authorization safety studies. In this non-interventional post-authorization study, we explored if vildagliptin is associated with an increased risk of hepatic events vs. other non-insulin antidiabetic drugs (NIADs) in a real-world setting. A cohort study was performed in adult T2DM patients with a vildagliptin or NIAD prescription between January 20and June 2014 with data from five European electronic healthcare databases from the UK (CPRD), Germany and France (IMS), Denmark (OPED) and Sweden (National Registers). Patients with cancer, HIV/AIDS or insulin prior to the index date (date of first vildagliptin or NIAD prescription in the study period) were excluded. Age- and sex-adjusted incidence rate ratios (aIRRs) were estimated in current vildagliptin vs. current other NIAD users using negative binomial regression. We included 738,054 patients, of which 20,973 received vildagliptin (mean follow-up 1.4 years, 28,330 cumulative vildagliptin patient-years). The database-specific aIRR estimates for serious hepatic events were not suggestive of an increased risk with vildagliptin (range of individual aIRR: 0.29-0.55), with two data sources having an upper limit of the 95% confidence interval (CI) <1 (IMS Germany: 0.65; IMS France: 0.63). The aIRR for ALT/AST >3-times upper limit of normal (ULN) together with bilirubin >2-times ULN (only assessed in CPRD) was 0.72 (95% CI: 0.42-1.25). In this real-world setting there was no evidence of an increased risk of hepatic toxicity with vildagliptin exposure compared to other NIADs across five European databases.
R. Williams: Employee; Self; Clinical Practice Research Datalink, London, UK. W. Kothny: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. C. Serban: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. P.M. Paldánius: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. R. Schlienger: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG.