Metformin Significantly Affects Metabolic Pathways in Type 2 Diabetes

In addition to previous findings stating that metformin lowers the levels of LDL cholesterol, this oral type 2 diabetes (T2D) drug also influences the body’s nitrogen and urea metabolism, a recent study found.

In a collaborative effort, researchers examined the metabolite profiles (353 small molecules) of KORA participants. Researchers compared 74 T2D patients treated with metformin with 115 patients not treated with metformin, and looked for differences in the distribution of metabolites in the blood. The findings were published in Diabetes.

Changes in the amino acid citrulline concentration caused by metformin intake were also found to be significant. Citrulline showed significantly lower levels in the T2D patient samples treated with metformin than in the untreated samples.

The authors noted that this may be an additional consequence of metformin’s AMPK activation.

“Our analysis indicated that the activation of the AMPK pathway by metformin affects nitrogen and urea metabolism through a further enzyme, which thus lowers the citrulline levels,” said researcher Rui Wang-Sattler.

Researchers hypothesize that the additional intake of citrulline could have a positive effect on the cardiovascular system in patients treated with metformin, and plan to conduct a follow-up study to analyze the metformin-associated effects on other metabolic pathways, such as the citric acid cycle.