Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial.

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.

• Authors: Thananda Trakarnvanich, Bancha Satirapoj, Swangjit Suraamornkul, Thanit Chirananthavat, Anoma Sanpatchayapong, Torpong Claimon
• Journal: Journal of diabetes research (J Diabetes Res) Vol. 2021 Pg. 7382620 ( 2021) ISSN: 2314-6753 [Electronic] England
• PMID: 34697593 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2021 Thananda Trakarnvanich et al.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• FABP1 protein, human
• Fatty Acid-Binding Proteins
• HAVCR1 protein, human
• Hepatitis A Virus Cellular Receptor 1
• LC15-0444
• LCN2 protein, human
• Lipocalin-2
• Piperidones
• Pyrimidines
• Reactive Oxygen Species
• SPP1 protein, human
• Osteopontin
• Alkaline Phosphatase

Topics

• Aged
• Alkaline Phosphatase (metabolism)
• Ankle Brachial Index
• Coronary Artery Disease (diagnostic imaging, physiopathology)
• Diabetes Mellitus, Type 2 (complications, drug therapy, metabolism, physiopathology)
• Diabetic Nephropathies (drug therapy, etiology, metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
• Fatty Acid-Binding Proteins (metabolism)
• Female
• Glomerular Filtration Rate
• Hepatitis A Virus Cellular Receptor 1 (metabolism)
• Humans
• Lipocalin-2 (metabolism)
• Male
• Middle Aged
• Osteopontin (metabolism)
• Piperidones (therapeutic use)
• Pulse Wave Analysis
• Pyrimidines (therapeutic use)
• Reactive Oxygen Species (metabolism)
• Vascular Calcification (diagnostic imaging, physiopathology)