Thiazolidinediones and Risk of Atrial Fibrillation Among Patients with Diabetes and Coronary Disease

Am J Med. 2018 Jul;131(7):805-812. doi: 10.1016/j.amjmed.2018.02.026. Epub 2018 Mar 23.


Background: We sought to determine whether insulin-sensitizing therapy (thiazolidinediones or metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a meglitinide). Thiazolidinediones are insulin sensitizers that also decrease the inflammatory response. Because inflammation is a risk factor for atrial fibrillation, we hypothesized that treating diabetes with thiazolidinediones might decrease the risk of developing atrial fibrillation.

Methods: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease. All patients were randomized to insulin-sensitizing therapy or insulin-providing therapy.

Results: A total of 2319 patients entered the study, with 1160 assigned to the insulin-sensitization strategy and 1159 assigned to the insulin-provision strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new-onset atrial fibrillation. In the intention-to-treat analysis, the incidence of atrial fibrillation was 8.7 per 1000 person-years in patients assigned to insulin sensitization compared with 9.5 in patients assigned to insulin provision with a hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38, P = .66). In a time-varying exposure analysis, the incidence rate per 1000 person-years was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a subset of patients matched on propensity to receive a thiazolidinediones, the HR was 0.75 (95% CI, 0.43-1.30, P = .30).

Conclusions: We did not find a significant reduction of atrial fibrillation incidence with use of thiazolidinediones.

Keywords: Atrial fibrillation; Diabetes mellitus; Insulin providers; Insulin sensitizers; Thiazolidinediones.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrial Fibrillation / chemically induced*
  • Coronary Disease / complications
  • Coronary Disease / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Intention to Treat Analysis
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Propensity Score
  • Risk Factors
  • Thiazolidinediones / adverse effects*
  • Treatment Outcome


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Metformin