# Complementary Yet Distinct Roles of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Cardiovascular Risk Reduction

## TL;DR

This paper compares how two diabetes drugs, GLP-1 receptor agonists and SGLT2 inhibitors, reduce cardiovascular risks through different mechanisms and helps guide their use in patients.

## Contribution

The paper provides a comparative summary of GLP-1 receptor agonists and SGLT2 inhibitors, focusing on their cardiovascular benefits and clinical decision factors.

## Key findings

- GLP-1 receptor agonists reduce cardiovascular risk via anti-atherosclerotic effects like improving endothelial function and reducing inflammation.
- SGLT2 inhibitors lower cardiovascular risk by increasing sodium excretion and reducing oxidative stress and uric acid levels.
- Combining GLP-1 receptor agonists and SGLT2 inhibitors may offer additional cardiovascular benefits but requires careful consideration of adverse effects.

## Abstract

Novel antidiabetic drugs introduced in the last decade have not only revolutionized the treatment of type 2 diabetes mellitus but have also changed our cardiovascular risk reduction strategy. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce the risk of atherosclerotic diseases primarily through their complex anti-atherosclerotic effect due to their endothelial function-improving, anti-inflammatory, anti-thrombotic, and plaque-stabilizing effects. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, on the other hand, have a favorable cardiovascular effect, mainly by increasing sodium excretion, reducing plasma volume, enhancing the use of ketone bodies as metabolic substrates in heart and kidney tissues, and reducing oxidative stress and uric acid serum levels. However, when using these two groups of drugs, important questions arise. What criteria should be used to decide on the administration of one or the other class of drugs? Which group of agents can be used more effectively to reduce our patients’ cardiovascular risk? What are the possible adverse effects? What can be gained by combining the two drugs? Our objective was to provide a current literature-based and comparative summary on the mechanisms of action, cardiovascular-risk-reducing efficacy, and safety profiles of these two drug classes, with an emphasis on identifying key factors influencing everyday clinical decision-making.