Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction

Research output: Contribution to journalArticlepeer-review

Abstract

Background: No study has compared the cardiovascular outcomes for sodium–glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)—which also have cardiovascular benefits—in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Methods: Medicare fee-for-service data (2013–2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting. Results: Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses. Conclusions: Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.

Original languageAmerican English
Article number54
JournalCardiovascular Diabetology
Volume22
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Keywords

  • Cardiovascular outcomes
  • Glucagon-like peptide-1 receptor agonists
  • Heart failure
  • Hospitalization for heart failure
  • Major adverse cardiovascular events
  • Myocardial infarction
  • Sodium–glucose cotransporter-2 inhibitors
  • Stroke

Fingerprint

Dive into the research topics of 'Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction'. Together they form a unique fingerprint.

Cite this