Incretin-based drugs and the risk of heart failure


Incretin-based drugs are medications prescribed to lower blood sugar levels in patients with type 2 diabetes. There has been concern, however, that these medications may increase the risk of heart failure. This CNODES study examined whether the use of incretin-based drugs increases the risk of heart failure in patients with type 2 diabetes.

This study included administrative data from four Canadian provinces (Alberta, Manitoba, Ontario, and Saskatchewan) and two international databases (United Kingdom Clinical Practice Research Datalink and United States MarketScan). Using a common protocol, site-specific cohorts were created of patients who received a new prescription for an antidiabetic drug after the date that incretin-based drugs became available within their jurisdiction. Separate cohorts were created of patients with and without a history of heart failure. The outcome of interest was a hospitalization for heart failure. Patients prescribed incretin-based drugs were compared to patients prescribed combinations of other oral antidiabetic drugs.

Within each cohort, a nested case-control analysis with risk-set sampling was used to match cases to controls. Hazard ratios (HRs) were estimated using conditional logistic regression models, with adjustment for potential confounders. Site-specific results were meta-analyzed using random-effects models with inverse variance weighting.


The health records of 1,499,650 patients were included in this study; 29,741 of which were hospitalized for heart failure during the follow-up period (resulting in an incidence rate of 9.2 per 1,000 patients per year). Compared to those prescribed combinations of other oral antidiabetic drugs, the risk of heart failure was not increased in those taking incretin-based drugs. This held true for patients with (adjusted HR = 0.86; 95% CI = 0.62, 1.19) and without a history of heart failure (adjusted HR = 0.82; 95% CI = 0.67, 1.00). Similarly, there was no association with duration of use or class of incretin-based drug.

The results of this large international study indicate that the use of incretin-based drugs is not associated with an increased risk of heart failure relative to combinations of oral antidiabetic drugs. These findings should provide some reassurance regarding the heart failure risk of these drugs.

Project Team

Project Co-Lead

Pierre Ernst

Project Co-Lead

Kristian Filion

Methods Lead

Robert Platt

Content Expert

Kristin Clemens

Lead Analyst

Matt Dahl


  • Tanvir Chowdhury TurinAlberta
  • Laurent AzoulayCPRD
  • Laura TargownikManitoba
  • Colin DormuthMarketScan
  • Jacob UdellOntario
  • Michael PatersonOntario
  • Nianping HuSaskatchewan


  • James ZhangAlberta
  • Zhihai MaAlberta
  • Hui YinCPRD
  • Matt DahlManitoba
  • Greg CarneyMarketScan
  • Simon HollandsOntario
  • Fangyun WuOntario
  • Shan JinSaskatchewan

Additional Collaborators

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