Effect of treatment with GLP-1R agonists on the urinary peptidome of T2DM patients

Type II diabetes mellitus (T2DM) accounts for approximately 90% of all diabetes mellitus cases in the world. Glucagon-like peptide-1 receptor (GLP-1R) agonists have established an increased capability to target directly or indirectly six core defects associated with T2DM, while, the underlying molecular mechanisms of these pharmacological effects are not fully known. This exploratory study was conducted to analyze the effect of treatment with GLP-1R agonists on urinary peptidome of T2DM patients. Urine samples of thirty-two T2DM patients from the PROVALID study (A Prospective Cohort Study in Patients with T2DM for Validation of Biomarkers) collected at pre- and post-treatment with GLP-1R agonist drugs were analyzed by CE-MS. In total, 70 urinary peptides were significantly affected by GLP-1R agonist treatment; generating from 26 different proteins. The downregulation of MMP proteases, based on the concordant downregulation of urinary collagen peptides was highlighted. Treatment also resulted in downregulation of peptides from SERPINA1, APOC3, CD99, CPSF6, CRNN, SERPINA6, HBA2, MB, VGF, PIGR and TTR, many of which were previously found to be associated with increased insulin resistance and inflammation. The findings indicate potential molecular mechanisms of GLP-1R agonists in the context of management of T2DM and prevention or delaying the progression of its associated diseases.