Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease

Abstract

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD).

Objective: To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD.

Design: Population-based cohort study.

Setting: Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017).

Participants: 1:1 propensity score-matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy.

Measurements: Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates.

Results: The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, -2.47 [CI, -4.45 to -0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, -0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, -4.97 [CI, -6.55 to -3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, -0.58 [CI, -0.91 to -0.25]).

Limitation: Treatment selection was not randomized.

Conclusion: Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD.

Primary funding source: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.

Figure 1.. Cumulative incidence function plots for primary outcomes comparing PS-matched SGLT2i vs. GLP-1RA initiators by history of cardiovascular disease* and overall

PS: propensity-score; SGLT2i: sodium-glucose cotransporter-2 inhibitors; GLP-1RA: glucagon-like peptide-1 receptor agonists. * History of cardiovascular disease is defined as history of myocardial infarction, angina, coronary atherosclerosis and other forms of chronic ischemic heart disease, coronary procedure, heart failure, ischemic stroke, peripheral arterial disease or surgery, lower extremity amputation † Hospitalization for myocardial infarction, or ischemic or hemorrhagic stroke

Figure 2.. Primary and secondary outcomes in 1:1 PS-matched initiators of SGLT2i vs GLP-1RA by history of cardiovascular disease* and overall

PS: propensity score; SGLT2i: sodium-glucose cotransporter-2 inhibitors; GLP-1RA: glucagon-like peptide-1 receptor agonists; IR: Incidence rate; PY: person-years; HR: hazard ratio; CI: confidence intervals; RD: rate difference; CVD: cardiovascular disease. * History of cardiovascular disease is defined as history of myocardial infarction, angina, coronary atherosclerosis and other forms of chronic ischemic heart disease, coronary procedure, heart failure, ischemic stroke, peripheral arterial disease or surgery, lower extremity amputation † Hospitalization for myocardial infarction, or ischemic or hemorrhagic stroke ‡ Hospitalization for myocardial infarction, ischemic or hemorrhagic stroke, or all-cause mortality