Renoprotective effects of dulaglutide, a GLP-1 agonist, involving regulation of epithelial-mesenchymal transition in patients with type 2 diabetes and diabetic kidney disease

To assess the renoprotective effects of dulaglutide and identify mechanisms of action in patients with type 2 diabetes and diabetic kidney disease (DKD). Outpatients/ambulant patients at the Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University between October 2021 and July 2023, with type 2 diabetes and DKD, a urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol and who were receiving hypoglycemic agents were prescribed dulaglutide at a dose rate of 0.75 - 1.5 mg once weekly (intervention group; n = 70). Patients receiving hypoglycemic agents other than glucagon-like peptide-1 (GLP-1) receptor agonists and who were not prescribed dulaglutide constituted the control group (n = 65). Observations/outcomes: The primary outcome was a change in the UACR and biomarkers of epithelial-mesenchymal transition (EMT) determined after 12 months of intervention treatment. Adverse events (estimates of tolerability and safety) were recorded during treatment and a follow-up period of 12 months. UACR changes in the intervention group compared to the control group were significantly lower (p < 0.01 at 6 months and p < 0.05 at 12 months). The frequency of gastrointestinal adverse events in the two groups were not significantly different, and there were no significant increases in the number of hypoglycemic events. Dulaglutide significantly increased the epithelial marker E-cadherin and inhibited the mesenchymal marker periostin. It is concluded that dulaglutide causes significant reductions in urinary albumin and modulates EMT-related proteins thereby ameliorating the decline in kidney function in patients with type 2 diabetes and DKD.