Hospitalisation for heart failure and mortality associated with dipeptidyl peptidase 4 (DPP-4) inhibitor use in an unselected population of subjects with type 2 diabetes: a nested case-control study

BMJ Open. 2015 Jun 5;5(6):e007959. doi: 10.1136/bmjopen-2015-007959.

Abstract

Objective: The SAVOR TIMI-53 study reported a significant increase in the risk of hospitalisation for heart failure (HF) in patients treated with a DPP-4 inhibitor (DPP-4i) in comparison with placebo. A recent case-control study in part confirmed this risk signal. Our aim was to compare the occurrence of HF in relation to DPP-4i use versus any antidiabetic treatment.

Design: Population-based matched case-control study conducted using administrative data.

Setting: The Italian Region of Piedmont (4.4 million inhabitants).

Participants: From a database of 282,000 patients treated with antidiabetic drugs, we identified 14,613 hospitalisations for HF, 7212 incident cases, and 1727 hospital re-admissions between 2008 and 2012; each case was matched for gender, age and antidiabetic therapy with 10 controls; cases and controls were compared for exposure to DPP-4i.

Outcome measures: ORs and 95% CIs were calculated by fitting a conditional logistic model. All analyses were adjusted for available risk factors for HF.

Results: We found no increased risk of hospitalisation for HF associated with the use of DPP-4i (OR for admission for HF 1.00 (0.94 to 1.07), incident HF1.01 (0.92 to 1.11), recurrent HF 1.02 (0.84 to 1.22)). All-cause mortality was 6% lower in DPP-4i users (p<0.001), whereas insulin users showed an excess of risk for any type of hospital admission (19%) and death (20%) (p<0.001).

Conclusions: Our findings suggest that, in an unselected population of diabetic patients, the use of DPP-4i is not associated with an increased risk of HF. The favourable impact on all-cause mortality should be viewed with caution and also other explanations investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / mortality
  • Diabetic Angiopathies / prevention & control
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / prevention & control
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Male
  • Risk Factors
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents