Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors and the risk of heart failure: A nationwide cohort study of older adults with diabetes mellitus

Diabetes Obes Metab. 2021 Apr;23(4):950-960. doi: 10.1111/dom.14300. Epub 2021 Jan 13.

Abstract

Aims: To analyse the rate of heart failure hospitalization for older adults prescribed a sodium-glucose co-transporter-2 (SGLT2) inhibitor.

Materials and methods: The study cohort included adults aged 66 years and older diagnosed with diabetes mellitus in Ontario, Canada, between July 2015 and March 2019, who received either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor. The primary outcome was a composite of heart failure hospitalization and all-cause mortality. Secondary outcomes included diabetic ketoacidosis and hypoglycaemia.

Results: A total of 29 916 adults prescribed an SGLT2 inhibitor were compared with 29 916 adults prescribed a DPP-4 inhibitor. The mean age was 72 years, 60% were men, the baseline glycated haemoglobin concentration was 8.2% and the baseline creatinine was 89 μmol/L. The incidence rate of the primary outcome was 19/1000 person-years for adults prescribed an SGLT2 inhibitor compared to 38/1000 person-years in those prescribed a DPP-4 inhibitor. This resulted in a hazard ratio (HR) of 0.49 (95% confidence interval [CI] 0.45, 0.54) and a rate difference (RD) of 19 fewer events per 1000 person-years (RD -19 [95% CI -22, -17]). Patients prescribed an SGLT2 inhibitor also had a lower rate of hypoglycaemia (HR 0.61 [95% CI 0.46, 0.81); RD -1.6 [95% CI -2.4, -0.8]), but a higher rate of diabetic ketoacidosis (HR 1.84 [95% CI 1.26, 2.70]; RD 1.0 [95% CI 0.4, 1.6]).

Conclusions: Older adults prescribed an SGLT2 inhibitor had a lower rate of heart failure hospitalization or death, and a lower rate of hypoglycaemia, but an increased rate of diabetic ketoacidosis compared to older adults prescribed a DPP-4 inhibitor.

Keywords: DPP-4 inhibitor; SGLT2 inhibitor; antidiabetic drug; cardiovascular disease; cohort study; heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose
  • Heart Failure* / epidemiology
  • Humans
  • Male
  • Ontario / epidemiology
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Symporters*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors
  • Symporters
  • Sodium
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose