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