Annals of internal medicineSep 27, 2021

Heart Risk with Sodium-Glucose Transporter-2 Inhibitors Compared to Glucagon-like Peptide-1 Receptor Agonists in Diabetes Patients with Different Heart Disease Levels

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

The initiation of SGLT2 inhibitor therapy is associated with a 4.97 per 1000 person-years reduction in heart failure hospitalization risk for patients with cardiovascular disease.

SGLT2 inhibitors were linked to a lower risk of myocardial infarction or stroke in patients with cardiovascular disease compared to GLP-1 receptor agonists.
There was no significant difference in the risk of myocardial infarction or stroke for patients without cardiovascular disease when comparing the two treatments.
Both SGLT2 inhibitors and GLP-1 receptor agonists reduced the risk of hospitalization for heart failure in patients with cardiovascular disease.
SGLT2 inhibitors also reduced heart failure hospitalization risk in patients without cardiovascular disease, but the absolute benefit was smaller.
Findings indicate that while SGLT2 inhibitors may offer cardiovascular benefits, the extent of these benefits differs based on the presence of cardiovascular disease.

Simplified

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.

Heart Risk with Sodium-Glucose Transporter-2 Inhibitors Compared to Glucagon-like Peptide-1 Receptor Agonists in Diabetes Patients with Different Heart Disease Levels

Abstract

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief