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Effect of switching to teneligliptin from other dipeptidyl peptidase-4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease.

ABSTRACT: AIMS/INTRODUCTION:The objective of the present study was to elucidate the effect of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors on glucose control and renoprotection in type 2 diabetes mellitus patients with diabetic kidney disease. MATERIALS AND METHODS:The present study was a single-arm, open-label, observational study. A total of 23 patients, who had urinary albumin/creatinine ratios (UACR) ?30 mg/gCr in their first urine in the early morning, and received other DPP-4 inhibitors and renin-angiotensin system inhibitors, switched to teneligliptin 20 mg/day. After switching to teneligliptin for 24 weeks, we evaluated changes in glycated hemoglobin (HbA1c), fasting plasma glucose levels, plasma DPP-4 activity and UACR. RESULTS:HbA1c, fasting plasma glucose and UACR values showed no significant change after 24 weeks compared with baseline. However, plasma DPP-4 activity was significantly reduced after 24 weeks (0.57 ± 0.26 nmol/min/mL, P = 0.012, vs baseline), compared with baseline (1.49 ± 1.73 nmol/min/mL), and there was a positive relationship between the change rate of plasma DPP-4 activity (?%DPP-4) for 24 weeks and the levels of plasma DPP-4 activity (r = -0.5997, P = 0.0025) and fasting plasma glucose (r = -0.4235, P = 0.0440) at baseline. Additionally, the ?%DPP-4 for 24 weeks was significantly correlated to the change rate of UACR (r = 0.556, P = 0.0059). However, there was no relationship between ?%DPP-4 and ?HbA1c (amount of HbA1c change). CONCLUSIONS:Switching to teneligliptin from other DPP-4 inhibitors for 24 weeks reduces plasma DPP-4 activity, which is associated with a reduction in albuminuria, independent of the change in glucose levels, in type 2 diabetes mellitus patients with diabetic kidney disease.

SUBMITTER: Kitada M

PROVIDER: S-EPMC6497591 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Effect of switching to teneligliptin from other dipeptidyl peptidase-4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease.

Kitada Munehiro M Ogura Yoshio Y Nitta Kyoko K Fujii Mizue M Kanasaki Keizo K Konishi Kazunori K Iida Yasuo Y Nakagawa Atsushi A Koya Daisuke D

Journal of diabetes investigation 20181001 3

<h4>Aims/introduction</h4>The objective of the present study was to elucidate the effect of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors on glucose control and renoprotection in type 2 diabetes mellitus patients with diabetic kidney disease.<h4>Materials and methods</h4>The present study was a single-arm, open-label, observational study. A total of 23 patients, who had urinary albumin/creatinine ratios (UACR) ≥30 mg/gCr in their first urine in the early morning ...[more]

PMID: 30136384

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Project description:Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

Dataset Information

Effect of switching to teneligliptin from other dipeptidyl peptidase-4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease.

Publications

Effect of switching to teneligliptin from other dipeptidyl peptidase-4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease.

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