Bidirectional modulation of the citric acid (TCA) cycle metabolites and anaplerosis by metformin and its combination with SGLT2i
Authors' conclusion
This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.
Study context
- Population
- db/db diabetic mice; human T2D patients in two cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve T2D patients
- Comparison
- Metformin monotherapy vs vehicle in db/db mice; SGLT2i + metformin vs metformin; metformin-treated vs untreated T2D patients
- Outcome
- Metabolites of the TCA cycle and anaplerotic pathways in plasma, liver and kidney
- Follow-up
- Post-treatment
Methodological detailsmouse and human cohorts, metabolic profiling of 716 metabolites, Bonferroni correction
- Mouse and human cohorts
- Metabolic profiling of 716 metabolites
- Bonferroni correction
Main finding
As reported in the abstract
- Metformin monotherapy significantly upregulated plasma malate, fumarate and α-KG, hepatic glutamate and renal 2-HG in diabetic mice
- Downregulated hepatic taurine with metformin
- Addition of SGLT2i reversed these effects: downregulated circulating malate and α-KG, hepatic glutamate and renal 2-HG; upregulated hepatic taurine
- In human T2D patients on metformin, increased malate but decreased citrulline
Original publication
Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i. Cardiovasc Diabetol. Published 12 June 2024. doi:10.
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