OBJECTIVES: In 2009, the US Food and Drug Administration (FDA) initiated a routine prospective surveillance study using the Mini-Sentinel (M-S) program to assess potential signals of acute myocardial infarction (AMI) with use of saxagliptin, an antihyperglycemic drug of the dipeptydal-peptidase 4 (DPP-4) inhibitor class, designated for the treatment of type 2 diabetes, compared with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin.

METHODS: We utilized the TriNetX federated network of de-identified health data to identify saxagliptin users from August 2009-August 2014. TriNetX identified 28,387 potential saxagliptin patients using RxNorm terminology occurring on or after August 1, 2009. We also identified 4 separate comparator cohorts of sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin patients. Users of saxagliptin and comparators were analyzed per the widely available M-S protocol and were 1:1 propensity score-matched to adjust for potential confounders. Hazard ratios (HR) were evaluated for significance using 95% confidence intervals (CI).

RESULTS: 28,387 saxagliptin patients, 372,998 sitagliptin patients, 161,233 pioglitazone patients, 953,970 second-generation sulfonylureas patients, and 1,264,555 long-acting insulin patients were identified. The adjusted HR with 95% CI was 0.98 (0.895,1.077) in the comparison with sitagliptin, 1.07 (0.971,1.174) in the comparison with pioglitazone, 0.88 (0.809,0.97) in the comparison with second-generation sulfonylureas, and 0.74 (0.683,0.817) in the comparison with long-acting insulin. None of the pairwise comparisons suggested an increased risk of AMI for saxagliptin users.

CONCLUSIONS: Using the M-S protocol and analysis with an electronic medical record network data source, there was no statistically significant increased risk of AMI found among saxagliptin users compared with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin. These findings were consistent with those of the FDA M-S saxagliptin study.