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Redefining SGLT2 inhibitors through cytoprotective mechanisms
Sanja Stankovic1, Zoran Miloradovic2, Vladimir Petrovic3
1Department of Pharmacology, University of Nis School of Medicine, Nis, Serbia.
European Journal of Pharmacology
|February 6, 2026
Summary
Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer benefits beyond diabetes management. These drugs promote cellular health and may protect against cardiovascular and renal diseases through mechanisms independent of glucose lowering.
Area of Science:
- Pharmacology
- Cellular Metabolism
- Endocrinology
Background:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are established type 2 diabetes treatments.
- Evidence suggests SGLT2 inhibitors have pleiotropic effects beyond glycemic control.
Purpose of the Study:
- To review the molecular mechanisms of SGLT2 inhibitors' extraglycemic actions.
- To link these mechanisms to clinical trial data and explore therapeutic repurposing.
Main Methods:
- Literature review of experimental and clinical studies.
- Analysis of cellular pathways influenced by SGLT2 inhibitors.
- Correlation of mechanistic insights with ongoing clinical trials.
Main Results:
- SGLT2 inhibitors promote ketogenesis and upregulate sirtuin 1.
- They attenuate inflammation and oxidative stress via AMPK-mTORC1 signaling.
- These actions suggest cytoprotective properties.
Conclusions:
- SGLT2 inhibitors possess extraglycemic benefits.
- These benefits may underlie their efficacy in cardiovascular and renal diseases.
- Expanded therapeutic potential beyond diabetes is indicated.
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