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

Ziad Arow1,2, Tzipi Hornik-Lurie3, Ranin Hilu1,2

  • 1Cardiology Department, Meir Medical Center, 59 Tchernichovsky St, 44281, Kfar Saba, Israel.

Cardiovascular Diabetology
|August 31, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide-1 receptor agonists (GLP-1RA) significantly reduce mortality in type 2 diabetes patients with cardiovascular disease. Combining SGLT2-I and GLP-1RA offers the greatest survival benefit, yet undertreatment persists.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2D) and atherosclerotic cardiovascular disease (ASCVD) represent a significant global health burden.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for cardiovascular risk reduction in T2D patients.
  • Despite proven benefits, the utilization of SGLT2-I and GLP-1RA in high-risk T2D patients remains suboptimal.

Purpose of the Study:

  • To investigate real-world treatment patterns of SGLT2-I and GLP-1RA in patients with T2D and established ASCVD.
  • To evaluate the association between the use of SGLT2-I and GLP-1RA, individually or in combination, and all-cause mortality.
  • To identify factors associated with the undertreatment of these cardioprotective medications.

Main Methods:

  • A large cohort study (CARdiovascular and DIABetes - CARDIAB) of 138,397 patients with T2D and ASCVD was analyzed.
  • Patients were stratified into four groups based on their medication use: SGLT2-I and GLP-1RA combination, SGLT2-I monotherapy, GLP-1RA monotherapy, or neither agent.
  • All-cause mortality was the primary endpoint, with hazard ratios (HR) and 95% confidence intervals (CI) calculated.

Main Results:

  • The majority of patients (57%) received neither SGLT2-I nor GLP-1RA, while 17% received both, 20% received SGLT2-I only, and 6% received GLP-1RA only.
  • Lower rates of SGLT2-I and GLP-1RA use were observed in females, older individuals, those with non-coronary ASCVD, and patients not followed in specialized clinics.
  • Treatment with SGLT2-I only (HR 0.28), GLP-1RA only (HR 0.39), and the combination therapy (HR 0.17) was associated with significantly lower all-cause mortality compared to no use of these agents.

Conclusions:

  • Combination therapy with SGLT2-I and GLP-1RA demonstrates a substantial mortality benefit in T2D patients with ASCVD.
  • Significant disparities in the implementation of evidence-based SGLT2-I and GLP-1RA therapies exist in clinical practice.
  • Optimizing the use of SGLT2-I and GLP-1RA is crucial for improving outcomes in this high-risk patient population.
Keywords:
Atherosclerotic cardiovascular diseaseGlucagon-like peptide-1 receptor agonists (GLP-1RA)Sodium-glucose cotransporter 2 inhibitors (SGLT2-I)Type 2 diabetes mellitus

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