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Metformin, Empagliflozin, and Their Combination Modulate Ex-Vivo Macrophage Inflammatory Gene Expression
Adittya Arefin1, Matthew C Gage2
1Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK.
International Journal of Molecular Sciences
|March 11, 2023
Summary
Metformin and empagliflozin, used for Type-2 Diabetes Mellitus, can directly impact macrophage inflammation. These drugs, alone or combined, modulate inflammatory gene expression and upregulate receptor expression in macrophages.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- Type-2 Diabetes Mellitus is a chronic condition requiring management of hyperglycemia.
- Metformin and empagliflozin are common anti-diabetic drugs, but their direct effects on macrophage inflammation are unknown.
Purpose of the Study:
- To investigate the direct effects of metformin and empagliflozin on macrophage inflammatory responses.
- To determine if these drugs modulate inflammatory gene expression and receptor signaling in macrophages.
Main Methods:
- Primary mouse bone-marrow-derived macrophages were treated with metformin and empagliflozin.
- In silico docking was used to predict receptor interactions.
- Gene expression of inflammatory markers and receptors was analyzed.
Main Results:
- Metformin and empagliflozin induced proinflammatory responses in macrophages as single agents.
- These responses were modulated when the drugs were used in combination.
- In silico analysis suggested empagliflozin interacts with TLR2 and DECTIN1 receptors.
- Both drugs increased the expression of Tlr2 and Clec7a (DECTIN1).
Conclusions:
- Metformin and empagliflozin directly modulate inflammatory gene expression in macrophages.
- The combination of these drugs alters macrophage inflammatory responses.
- These anti-diabetic drugs upregulate the expression of their potential target receptors, TLR2 and DECTIN1.

