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Abstract: TH-OR59

Effects of GLP-1 Receptor Agonist Dulaglutide on Profile of Circulating miRNAs Associated with ESKD in Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • McFarlin, Brandon E., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Tye, Sok Cin, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Ricca, Joseph, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

Glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to slow kidney function decline in patients with type 2 diabetes (T2D), but the underlying mechanism remains unclear. Circulating microRNAs (miRNAs) are short non-coding RNA molecules known to regulate proteins. Previously, we identified 17 plasma miRNAs (8 risk and 9 protective) that were predictive of end-stage kidney disease (ESKD) in T2D patients (Satake et al. JASN 2022). In this study, we investigated the treatment effect of the GLP-1 receptor agonist, Dulaglutide on longitudinal changes in plasma concentrations of these miRNAs in patients enrolled in the AWARD-7 trial.

Methods

Plasma samples were obtained from T2D patients with chronic kidney disease (CKD) stages 3-4 who received Dulaglutide 1.5 mg (n=29) or insulin Glargine (n=31) for 52 weeks. Using the HTG edgeSeq platform, we measured 17 ESKD-associated miRNAs at baseline and 52 weeks. Fold change (FC) values were calculated for each patient and each miRNA by dividing the concentration of miRNA at 52 weeks by its concentration at baseline.

Results

Comparing the FC values between Dulaglutide and Glargine groups, we observed that the plasma concentration of protective miRNAs (in blue) increased during Dulaglutide treatment, and 5 of them (miR-378d, -324-3p, -22-3p, -378a-3p and -339-5p) showed statistically significant increases (P<0.05). The plasma concentrations of all risk miRNAs (in red) were reduced with Dulaglutide treatment, but only the reduction of miR-6722-3p reached statistical significance (Figure).

Conclusion

Treatment of T2D patients with stage 3-4 CKD with Dulaglutide altered the profile of circulating miRNAs associated with ESKD, resulting in increased concentrations of protective miRNAs and decreased concentrations of risk miRNA in circulation.

Funding

  • NIDDK Support