SGLT2 inhibitors and GLP-1 receptor agonists: impact on mortality in diabetic patients with cardiovascular disease

🥈 Top 2% JournalAug 31, 2025Cardiovascular diabetology

How SGLT2 inhibitors and GLP-1 receptor agonists relate to death rates in diabetic patients with heart disease

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Abstract

Of the 138,397 patients with type 2 diabetes and atherosclerotic cardiovascular disease, 57% received neither SGLT2 inhibitors nor GLP-1 receptor agonists.

Patients treated with SGLT2 inhibitors only had a lower all-cause mortality rate (HR 0.28) compared to those receiving no treatment.
Those receiving GLP-1 receptor agonists only also demonstrated a significantly lower mortality rate (HR 0.39).
The combination of SGLT2 inhibitors and GLP-1 receptor agonists was associated with the lowest mortality rate (HR 0.17).
Lower treatment rates were linked to factors such as female sex, older age, non-coronary atherosclerotic cardiovascular disease, and lack of follow-up in specialized clinics.

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BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to reduce cardiovascular risk and mortality in patients with type 2 diabetes mellitus (T2D), yet remain underutilized in clinical practice. This study aimed to evaluate real-world treatment patterns and associated mortality outcomes among patients with T2D and established atherosclerotic cardiovascular disease (ASCVD).

METHODS: The CARdiovascular and DIABetes (CARDIAB) cohort included 138,397 patients with T2D and ASCVD. Patients were categorized into four treatment groups: (i) both SGLT2-I and GLP-1RA, (ii) SGLT2-I only, (iii) GLP-1RA only, and (iv) neither medication. The primary outcome was all-cause mortality.

RESULTS: Of the 138,397 patients, 57% received neither SGLT2-I nor GLP-1RA, 17% received both, 20% received SGLT2-I only, and 6% received GLP-1RA only. Female sex, older age, non-coronary ASCVD, and absence of follow-up in specialized cardiology or diabetes clinics were associated with lower treatment rates. Compared to those receiving neither medication, all-cause mortality was significantly lower among patients treated with SGLT2-I only (HR 0.28, 95% CI 0.27-0.29), GLP-1RA only (HR 0.39, 95% CI 0.37-0.40) and both agents (HR 0.17, 95% CI 0.16-0.18). This association remained significant following a multivariate analysis.

CONCLUSION: In patients with T2D and ASCVD, treatment with SGLT2-I and GLP-1RA, especially in combination, is associated with a substantial reduction in mortality. These findings highlight significant gaps in implementation and the urgent need to optimize use of evidence-based therapies in this high-risk population.

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