Comprehensive review of how metformin, SGLT2i, and GLP-1 drugs modulate cytokines and chemokines beyond glucose control | Research

The takeaway

Systematic review (2013-2025) characterizes the immunomodulatory profiles of metformin, SGLT2i, and GLP-1RAs, showing each class modulates distinct cytokine/chemokine networks that contribute to multi-organ protection beyond glycemic control.

Diabetes drugs are immune modulators
Each diabetes drug class (metformin, SGLT2i, GLP-1RA) modulates distinct cytokine/chemokine networks—their multi-organ benefits may come from immunomodulation, not just glucose control

What the researchers found

Three drug classes: distinct immunomodulatory profiles. Metformin: specific cytokine/chemokine modulation. SGLT2i: distinct immune effects. GLP-1RAs: specific immunomodulation. All: contribute to multi-organ protection beyond glucose. DM: metabolic + inflammatory disease.

Why it matters

Understanding each drug class's specific immune-modulating profile enables precision prescribing based on both metabolic and inflammatory needs—personalizing diabetes therapy.

How the study worked

Comprehensive review of cytokine and chemokine modulation by metformin, SGLT2i, and GLP-1RAs (2013-2025 literature).

What this study cannot tell us

Review format. Cytokine effects may differ in vitro vs in vivo. Individual patient responses vary. Cannot determine which cytokine effects are most clinically important.

How to read the evidence

Comprehensive review of 12 years of immunology data.

When this study was published

Published in 2025; covers 2013-2025.

The bigger picture

This reframes diabetes drugs as immune modulators. Their cardiovascular, renal, neurological, and liver benefits may all stem from specific cytokine/chemokine modulation rather than just glucose lowering.

Questions still open

Could cytokine profiling guide diabetes drug selection?
Which drug's immune profile best matches which complication?
Would combination therapy provide broader immunomodulation?

Common questions

Do diabetes drugs affect the immune system?

Yes—significantly. This review shows all three major diabetes drug classes (metformin, SGLT2 inhibitors, GLP-1 drugs) modulate different parts of the immune system through specific cytokine and chemokine effects. This immune modulation likely explains their benefits for the heart, kidneys, brain, and liver.

Is diabetes an inflammatory disease?

Increasingly, yes. Chronic inflammation contributes to diabetes complications affecting virtually every organ. This review shows modern diabetes drugs address both the metabolic (glucose) and inflammatory (immune) aspects of the disease, which may be equally important for preventing complications.

Read the original research

Immunomodulatory effects of anti-diabetic therapies: Cytokine and chemokine modulation by metformin, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists (2013-2025).

European journal of medicinal chemistry, 299, 118065

View on PubMed ↗Publisher’s paper ↗

Citation

Ullah, Amin; Shen, Bairong. (2025). Immunomodulatory effects of anti-diabetic therapies: Cytokine and chemokine modulation by metformin, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists (2013-2025).. European journal of medicinal chemistry, 299, 118065. https://doi.org/10.1016/j.ejmech.2025.118065