Cardiovascular outcomes associated with prescription of sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with diabetes and chronic kidney disease

Diabetes Obes Metab. 2022 May;24(5):928-937. doi: 10.1111/dom.14657. Epub 2022 Feb 16.

Abstract

Aim: To determine the association with cardiovascular (CV) outcomes of sodium-glucose co-transporter-2 (SGLT-2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).

Materials and methods: We conducted a population-based cohort study of new users of SGLT-2 inhibitors and DPP-4 inhibitors with T2D and CKD using data from Optum Clinformatics DataMart. We assembled three cohorts: T2D/no CKD, T2D/CKD 1-2, and T2D/CKD 3a. The study outcomes were (a) time to first heart failure (HF) hospitalization and (b) time to a composite CV endpoint comprised of non-fatal myocardial infarction (MI) or stroke. After inverse probability of treatment weighting, we used proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI).

Results: New users of SGLT-2 inhibitors versus DPP-4 inhibitors had lower risks of HF hospitalization in the T2D/no CKD (HR, 0.76; 95% CI, 0.70, 0.82) and T2D/CKD 1-2 (HR, 0.63; 95% CI, 0.48, 0.84) cohorts, but no significant association was present in the T2D/CKD 3a cohort. Compared with prescription of DPP-4 inhibitors, SGLT-2 inhibitors were associated with lower risks of non-fatal MI or stroke of 23% (HR, 0.77; 95% CI, 0.70, 0.85) in the T2D/no CKD cohort, but no significant associations were present in the T2D/CKD 1-2 and T2D/CKD 3a cohorts.

Conclusions: Incident prescription of SGLT-2 inhibitors was associated with lower risks of HF hospitalization but not with non-fatal MI or stroke despite suggesting benefit, relative to prescription of DPP-4 inhibitor across different stages of CKD.

Keywords: DPP-4 inhibitor; SGLT-2 inhibitor; antidiabetic drug; cardiovascular disease; chronic kidney disease; pharmaco-epidemiology; population study.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose
  • Humans
  • Hypoglycemic Agents
  • Prescriptions
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / epidemiology
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Symporters*

Substances

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