September 27, 2021Open Access
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
Key Result
SGLT2 inhibitors versus GLP-1 RAs were associated with lower MI or stroke risk in T2D patients with CVD (HR 0.90; 95% CI 0.82-0.98) and reduced heart failure hospitalization regardless of CVD.
Study Design
Type
Cohort (n=372,080)
Multicenter
Yes
Structured PICO
Does the initiation of SGLT2 inhibitors reduce the risk of MI, stroke, or heart failure hospitalization compared to GLP-1 RAs in adult T2D patients with and without baseline cardiovascular disease?
P
Population
372,080 adult type 2 diabetes patients with and without cardiovascular disease initiating SGLT2 inhibitor versus GLP-1 RA therapy.
E
Exposure
Initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy
C
Comparator
Initiation of glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy
O
Outcome
Myocardial infarction (MI) or stroke hospitalization, and hospitalization for heart failure (HHF)hard clinical
In routine clinical care, SGLT2 inhibitors are associated with a consistent reduction in heart failure hospitalization risk compared to GLP-1 RAs in patients with type 2 diabetes, regardless of baseline cardiovascular disease status.
Main Result
Hazard Ratio: 0.9 (95% CI 0.82–0.98)
Limitations
- Treatment selection was not randomized.
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.