Journal of the American Heart AssociationFeb 8, 2022

Heart and blood vessel benefits of diabetes drugs in older patients with or without heart disease or heart failure

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 29, 2026

Abstract

SGLT2 inhibitors are associated with a 65% reduction in hospitalized heart failure risk compared to GLP-1 receptor agonists in patients without cardiovascular disease or heart failure.

In patients with heart failure but no cardiovascular disease, SGLT2 inhibitors reduced the risk of hospitalization due to heart failure by 52%.
The combined risk of myocardial infarction, stroke, and mortality was higher for SGLT2 inhibitors compared to GLP-1 receptor agonists in patients without cardiovascular disease or heart failure.
SGLT2 inhibitors showed a favorable cardiovascular risk profile in individuals with a history of heart failure.
Atherosclerotic cardiovascular disease events were less common with GLP-1 receptor agonists in patients without a prior history of cardiovascular disease or heart failure.

Simplified

Background Randomized trials demonstrate the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). We evaluated their relative cardiovascular effectiveness in routine care populations with a broad spectrum of atherosclerotic cardiovascular diseases (CVDs) or heart failure (HF). Methods and Results We identified Medicare beneficiaries from 2013 to 2017, aged >65 years, initiating SGLT2i (n=24 747) or GLP-1RA (n=22 596) after a 1-year baseline. On the basis of diagnoses during baseline, we classified patients into: (1) no HF or CVD, (2) HF but no CVD, (3) no HF but CVD, and (4) both HF and CVD. We identified hospitalized HF and atherosclerotic CVD outcomes from drug initiation until treatment changes, death, or disenrollment. We estimated propensity score-weighted 2-year risk ratios (RRs) and risk differences, accounting for measured confounding, informative censoring, and competing risk. In patients with no CVD or HF, SGLT2i reduced the hospitalized HF risk compared with GLP-1RA (propensity score-weighted RR, 0.65; 95% CI, 0.43-0.96). The association was strongest in those who had HF but no CVD (RR, 0.48; 95% CI, 0.25-0.85). The combined myocardial infarction, stroke, and mortality outcome risk was slightly higher for SGLT2i compared with GLP-1RA in those without CVD or HF (RR, 1.31; 95% CI, 1.09-1.56). The association was favorable toward SGLT2i in subgroups with a history of HF. Conclusions SGLT2i reduced the cardiovascular risk versus GLP-1RA in patients with a history of HF but no CVD. Atherosclerotic CVD events were less frequent with GLP-1RA in those without prior CVD or HF.

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Heart and blood vessel benefits of diabetes drugs in older patients with or without heart disease or heart failure

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