Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study

PLoS One. 2019 Feb 11;14(2):e0211959. doi: 10.1371/journal.pone.0211959. eCollection 2019.

Abstract

Aim: To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database.

Methods: We identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in patients with type-2 diabetes. The main outcome was the hospitalization for HHF. Hazard ratios for HHF by type of second-line glucose-lowering medication were estimated by Cox-proportional hazard models. Sex, age, duration of MET monotherapy, Charlson Comorbidity Index and additional comorbidities, and calendar year were controlled as potential confounders.

Results: The observed numbers (rate per 100,000 person-years) of HHF events were 1,129 (658) for MET+SU users, 710 (455) for MET+DPP-4i users, and 110 (570) for MET+TZD users. Compared to that for MET+SU users (reference group), the adjusted hazard ratios for HHF events were 0.76 (95% confidence interval 0.69-0.84) for MET+DPP-4i users and 0.96 (95% confidence interval 0.79-1.17) for MET+TZD users.

Conclusion: DPP-4i as an add-on therapy to MET may lower the risks of HHF compared with SU.

Publication types

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

MeSH terms

  • Aged
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Heart Failure / epidemiology*
  • Heart Failure / prevention & control
  • Hospitalization / statistics & numerical data*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / administration & dosage*
  • Metformin / therapeutic use
  • Middle Aged
  • Republic of Korea
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Metformin
  • 2,4-thiazolidinedione

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI13C0715). KHIDI(https://www.khidi.or.kr/eps) the Ministry of Health and Welfare, Republic of Korea (http://www.mohw.go.kr/) The funder provided support in the form of salaries for authors DJ Kim, HC Kim. NO - The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.