Abstract
Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients with diabetic kidney disease (DKD). Methods This study employed a multicenter, prospective, randomized, placebo-controlled design. A total of 201 participants were enrolled and randomly assigned to one of two groups, one received treatment with 50 mg gemigliptin daily along with standard care for diabetes mellitus for 6 months. The changes in the coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (eGFR), vascular calcification level, and tubular renal injury marker expression were evaluated at baseline and 6 months. Results In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in the CAC score, CAVI, eGFR, and level of proteinuria over the 6 months of the study did not significantly differ between the gemigliptin and control groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the gemigliptin treatment group compared with the control group. No serious adverse events were observed during the study. Conclusion Our study showed that gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; however, gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. A larger study with a longer follow-up is essential to verify these beneficial effects. Clinical Trials. This trial is registered with ClinicalTrials.Gov Identifier NCT04705506.
Highlights
Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models
Treatment groups were balanced with respect to hypertensive medications used except for ACEi/ARB, which was more commonly used by patients in the gemigliptin group (63.3 vs. 46.0%, P = 0:02 in the gemigliptin and control groups, respectively)
We examined the effects of gemigliptin on the levels of urinary renal injury biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1)
Summary
Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. Our study showed that gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. Gemigliptin is a potent DPP-4 inhibitor that has been approved for use among patients with type 2 diabetes and provides pleiotropic effects in addition to its glucose-lowering effects. It inhibits lipopolysaccharide- (LPS-) induced proinflammatory effects in vascular endothelial cells by attenuating. A recent study revealed that gemigliptin attenuates calcification of the abdominal aorta, RUNX2- and Journal of Diabetes Research
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