Prospective Postmarketing Surveillance of Acute Myocardial Infarction in New Users of Saxagliptin: A Population-Based Study

Diabetes Care. 2018 Jan;41(1):39-48. doi: 10.2337/dc17-0476. Epub 2017 Nov 9.

Abstract

Objective: The cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI).

Research design and methods: We identified patients aged ≥18 years, starting from the approval date of saxagliptin in 2009 and continuing through August 2014, using data from 18 Mini-Sentinel data partners. We conducted seven sequential assessments comparing saxagliptin separately with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin, using disease risk score (DRS) stratification and propensity score (PS) matching to adjust for potential confounders. Sequential testing kept the overall chance of a false-positive signal below 0.05 (one-sided) for each pairwise comparison.

Results: We identified 82,264 saxagliptin users and more than 1.5 times as many users of each comparator. At the end of surveillance, the DRS-stratified hazard ratios (HRs) (95% CI) were 1.08 (0.90-1.28) in the comparison with sitagliptin, 1.11 (0.87-1.42) with pioglitazone, 0.79 (0.64-0.98) with sulfonylureas, and 0.57 (0.46-0.70) with long-acting insulin. The corresponding PS-matched HRs were similar. Only one interim analysis of 168 analyses met criteria for a safety signal: the PS-matched saxagliptin-pioglitazone comparison from the fifth sequential analysis, which yielded an HR of 1.63 (1.12-2.37). This association diminished in subsequent analyses.

Conclusions: We did not find a higher AMI risk in saxagliptin users compared with users of other selected antihyperglycemic agents during the first 5 years after U.S. Food and Drug Administration approval of the drug.

MeSH terms

  • Acute Disease
  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Dipeptides / therapeutic use*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Insulin, Long-Acting / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / epidemiology*
  • Pioglitazone
  • Product Surveillance, Postmarketing*
  • Propensity Score
  • Proportional Hazards Models
  • Prospective Studies
  • Sitagliptin Phosphate / therapeutic use
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • United States

Substances

  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • saxagliptin
  • Adamantane
  • Sitagliptin Phosphate
  • Pioglitazone