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Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for
Elisabetta Patorno1, Phyo T Htoo1, Robert J Glynn1
1Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (E.P., P.T.H., R.J.G., S.S., A.P., L.G.B., K.C., B.M.E., S.C.K.).
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.
Insights
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show similar risks for heart attack or stroke in type 2 diabetes patients. SGLT2 inhibitors consistently reduce heart failure hospitalization risk for all patients.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacoepidemiology
Background:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer cardiovascular benefits in type 2 diabetes (T2D) patients with established cardiovascular disease (CVD).
- Comparative effectiveness of these drug classes in T2D patients with and without pre-existing CVD requires further investigation.
Purpose of the Study:
- To compare the cardiovascular benefits of SGLT2 inhibitors versus GLP-1 RAs in T2D patients.
- To assess differential benefits based on the presence or absence of established cardiovascular disease (CVD).
Main Methods:
- A population-based cohort study utilizing Medicare and two U.S. commercial claims data sets (April 2013 to December 2017).
- 1:1 propensity score-matched adult T2D patients initiating SGLT2 inhibitor or GLP-1 RA therapy.
- Primary outcomes included hospitalization for myocardial infarction (MI), stroke, and heart failure (HHF); analyses controlled for 138 covariates.
Main Results:
- SGLT2 inhibitors showed a slightly lower risk for MI or stroke in patients with CVD, but similar risk in those without CVD.
- SGLT2 inhibitors significantly reduced HHF risk in both T2D patients with and without CVD, with a greater absolute benefit observed in those with CVD.
- No substantial differences in MI or stroke risk were observed between SGLT2 inhibitors and GLP-1 RAs across patient groups.
Conclusions:
- SGLT2 inhibitors demonstrate consistent reductions in heart failure hospitalization risk for T2D patients, irrespective of baseline CVD status.
- The risk of myocardial infarction or stroke appears comparable between SGLT2 inhibitors and GLP-1 RAs in T2D patients, regardless of CVD.
- Treatment selection for T2D patients should consider the specific benefits of SGLT2 inhibitors for heart failure prevention.
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