# Exploring the Effects of Metformin on the Body via the Urine Proteome

## TL;DR

This study explores how metformin affects the body by analyzing changes in the urine proteome of rats.

## Contribution

The study identifies 166 differential proteins in rat urine after metformin treatment, revealing new potential mechanisms of the drug.

## Key findings

- 166 differential proteins were identified in rat urine following metformin administration.
- Some proteins and pathways linked to metformin effects were previously known, while others are newly reported.
- The urine proteome approach provides a systematic way to study drug effects and mechanisms.

## Abstract

Metformin is the first-line medication for treating type 2 diabetes mellitus, with more than 200 million patients taking it daily. Its effects are extensive and play a positive role in multiple areas. Can its effects and potential mechanisms be explored through the urine proteome? In this study, 166 differential proteins were identified following the administration of 150 mg/(kg·d) of metformin to rats for five consecutive days. These included complement component C6, pyruvate kinase, coagulation factor X, growth differentiation factor 15, carboxypeptidase A4, chymotrypsin-like elastase family member 1, and L-lactate dehydrogenase C chain. Several of these proteins have been reported to be directly affected by metformin or associated with its effects. Multiple biological pathways enriched by these differential proteins, or proteins containing differentially modified peptides, have been reported to be associated with metformin, such as the glutathione metabolic process, negative regulation of gluconeogenesis, and the renin–angiotensin system. Additionally, some significantly changed proteins and enriched biological pathways, not yet reported to be associated with metformin’s effects, may provide clues for exploring its potential mechanisms. In conclusion, the application of the urine proteome offers a comprehensive and systematic approach to exploring the effects of drugs, providing a new perspective on the study of metformin’s mechanisms.