Risk of heart failure hospitalization among users of dipeptidyl peptidase-4 inhibitors compared to glucagon-like peptide-1 receptor agonists

Cardiovasc Diabetol. 2018 Jul 17;17(1):102. doi: 10.1186/s12933-018-0746-4.


Background: Incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon like peptide-1 (GLP-1) receptor agonists are novel medications for type 2 diabetes management. Several studies have found cardioprotective effects of incretin-based therapies; however, it remains unclear whether there is any difference in heart failure (HF) risk between the two incretin-based therapies (DPP-4 inhibitors and GLP-1 receptor agonists). We aimed to assess the risk of hospitalization due to HF with the use of DPP-4 inhibitors compared to GLP-1 receptor agonists.

Methods: Using Truven Health Marketscan data, we conducted a retrospective cohort study of patients with type 2 diabetes, who were newly initiated on DPP-4 inhibitors or GLP-1 agonists. Follow-up continued from drug initiation until the first occurrence of: HF hospitalization (primary outcome), discontinuation of therapy (i.e. no fill for 7 days), switch to the comparator, end of enrollment, or end of study (December 2013). Cox proportional hazards models with propensity-score-matching were used to compare the risk of HF hospitalization between DPP-4 inhibitors and GLP-1 agonists.

Results: A total of 321,606 propensity score-matched patients were included in the analysis (n = 160,803 for DPP-4 inhibitors; n = 160,803 for GLP-1 agonists). After adjusting for baseline characteristics and disease risk factors, the use of DPP-4 inhibitors was associated with a 14% decreased risk of HF hospitalization compared to GLP-1 agonists use [hazard ratio (HR), 0.86; 95% confidence interval (CI) 0.83, 0.90]. The results were consistent in patients without baseline HF (HR, 0.85; 95% CI 0.82, 0.89), but the association was not statistically significant for patients with baseline HF (HR, 0.90; 95% CI 0.74, 1.07).

Conclusion: In this retrospective matched cohort of patients with type 2 diabetes, the use of DPP-4 inhibitors was associated with a reduced risk of HF hospitalization compared to GLP-1 agonists. However, the association was not statistically significant in patients who had HF prior to the use of DPP-4 inhibitors.

Keywords: DPP-4 inhibitors; GLP-1 agonists; Heart failure; Safety; Type 2 diabetes.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Heart Failure / diagnosis
  • Heart Failure / etiology*
  • Heart Failure / prevention & control
  • Humans
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Male
  • Middle Aged
  • Patient Admission*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4