Endocrine Abstracts

JOINT462

Background and Objectives: The first clinically evident feature of renal involvement in diabetic kidney disease (DKD) is albuminuria and higher levels are associated with increased risk of chronic kidney disease (CKD) progression, thus treatments aimed at reducing albuminuria delay CKD progression. The incretin effect, mediated by glucagon-like peptide-1 (GLP-1), reduces kidney inflammation, fibrosis, and albuminuria, and its degradation is prevented by dipeptidyl peptidase-4 inhibitors (DPP4I) that are used in the treatment of type 2 DM. Renal effects of DPP4I include reduction in albuminuria and glomerulosclerosis. Given the potential of DPP4I in delaying the DKD progression, there is a need to summarize and review the current evidence.

Method: Computerized literature search of PubMed, CENTRAL, and ClinicalTrials. gov was done from inception to October 2024. Adults diagnosed with DM and any type of DPP4I evaluated for DKD were included. Primary outcomes included changes in urine albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Secondary outcomes included change in renal biomarkers for CKD progression including neutrophil gelatinase-associated lipocalin (NGAL), renal endpoints (doubling of serum creatinine, progression to ESRD, initiation of RRT, and renal related death). Subgroup analysis was done to examine differences in the effect estimates and heterogeneity by follow-up period and specific DPP4I used.

Results: 870 references were identified from the electronic search. 13 RCTs were included in the meta-analysis. The risk of bias of the studies were low to moderate. Meta-analysis showed significant reduction in UACR after treatment with DPP4I compared to control (7 RCTs, 20, 689 participants, MD -11. 06 mg/g Crea, 95% CI -21. 37 to -0. 75), however with high heterogeneity (I2=77%). Subgroup analysis based on follow-up period showed decrease in the heterogeneity in the subgroup with a follow-up period of 12-24 weeks (Chi2=3. 12, I2=0%) with significant decrease in UACR favoring DPP4I treatment (5 RCTs, 365 participants, MD -13. 36 mg/g Crea, 95% CI -20. 19 to -6. 52). Results showed no significant difference in change in eGFR and NGAL between treatment and control groups. None of the results evaluating the secondary outcomes were eligible for quantitative synthesis and failed to show difference between treatment and control.

Conclusion: This study found significant reduction of albuminuria with DPP4I treatment in patients with DKD, particularly in a short follow-up period of 6-12 months, suggesting DPP4I may be beneficial in delaying DKD progression. Limitations include a short follow-up period of the included RCTs precluding assessment of further effects of DPP4I on the prespecified renal endpoints.