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Drug/Regimen
A Multicentre, Multinational, Open-Label, 52-Week Extension Study of Gemigliptin (LC15-0444) Monotherapy in Patients with Type 2 Diabetes Mellitus
Sae Jeong Yang, Kyung Wan Min, Sandeep Kumar Gupta, Joong Yeol Park, Vyankatesh K.Shivane, Pankaj Kumar Agarwal, Doo Man Kim, Yong Seung Kim, Sei Hyun Baik
Diabetes Metab J. 2021;45(4):606-612.   Published online September 9, 2020
DOI: https://doi.org/10.4093/dmj.2020.0047
  • 5,054 View
  • 139 Download
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was –0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study
    Kyung-Soo Kim, Kyung Ah Han, Tae Nyun Kim, Cheol-Young Park, Jung Hwan Park, Sang Yong Kim, Yong Hyun Kim, Kee Ho Song, Eun Seok Kang, Chul Sik Kim, Gwanpyo Koh, Jun Goo Kang, Mi Kyung Kim, Ji Min Han, Nan Hee Kim, Ji Oh Mok, Jae Hyuk Lee, Soo Lim, Sang S
    Diabetes & Metabolism.2023; 49(4): 101440.     CrossRef
Original Article
Complications
Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome
Jung Beom Seo, Yeon-Kyung Choi, Hye-In Woo, Yun-A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
Diabetes Metab J. 2019;43(6):830-839.   Published online March 5, 2019
DOI: https://doi.org/10.4093/dmj.2018.0181
  • 5,452 View
  • 128 Download
  • 23 Web of Science
  • 24 Crossref
AbstractAbstract PDFPubReader   
Background

The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.

Methods

We examined the effects of gemigliptin on renal tubulointerstitial fibrosis induced in mice by unilateral ureteral obstruction (UUO). Using immunohistochemical and Western blot analysis, we quantitated components of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment, and in vitro in human kidney tubular epithelial human renal proximal tubule cells (HK-2) cells, we further analyzed the effect of gemigliptin on transforming growth factor-β (TGF-β)-stimulated production of profibrotic proteins.

Results

Immunohistological examination revealed that gemigliptin ameliorated UUO-induced tubular atrophy and renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1β, which had all been markedly increased by UUO. In line with the in vivo results, TGF-β markedly increased NLRP3 inflammasome markers, which were attenuated by gemigliptin treatment. Furthermore, gemigliptin treatment attenuated phosphorylated nuclear factor-κB levels, which had been increased in the UUO kidney as well as in TGF-β-treated cultured renal cells.

Conclusion

The present study shows that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis and the renoprotective effect of gemigliptin is associated with attenuation of NLRP3 inflammasome activation.

Citations

Citations to this article as recorded by  
  • Novel pharmacological interventions for diabetic kidney disease
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    Physiological Reviews.2023; 103(4): 2847.     CrossRef
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    Ageing Research Reviews.2022; 79: 101638.     CrossRef
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    Ying Chen, Hang Zou, Hongwei Lu, Hong Xiang, Shuhua Chen
    Journal of Cellular and Molecular Medicine.2022; 26(12): 3313.     CrossRef
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    Tianwei Meng, Hong Chang, Hongyu Meng
    Molecular Omics.2022; 18(9): 873.     CrossRef
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    Wan Seok Kang, Woo Kwon Jung, Su-Bin Park, Hyung Rae Kim, Junghyun Kim
    Biomedicine & Pharmacotherapy.2021; 137: 111297.     CrossRef
  • Long‐Term Dipeptidyl Peptidase 4 Inhibition Worsens Hypertension and Renal and Cardiac Abnormalities in Obese Spontaneously Hypertensive Heart Failure Rats
    Edwin K. Jackson, Zaichuan Mi, Delbert G. Gillespie, Dongmei Cheng, Stevan P. Tofovic
    Journal of the American Heart Association.2021;[Epub]     CrossRef
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    Yu Zhang, Ruicheng Zhang, Xiaohu Han
    Inflammation Research.2021; 70(5): 543.     CrossRef
  • Inflammasome as an Effective Platform for Fibrosis Therapy
    Ting-Ting Chen, Feng Xiao, Nan Li, Shan Shan, Meng Qi, Zi-Ying Wang, Sheng-Nan Zhang, Wei Wei, Wu-Yi Sun
    Journal of Inflammation Research.2021; Volume 14: 1575.     CrossRef
  • Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?
    Xin Huang, Yimin Khoong, Chengyao Han, Dai Su, Hao Ma, Shuchen Gu, Qingfeng Li, Tao Zan
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    Tsung-Jui Wu, Yi-Jen Hsieh, Chia-Wen Lu, Chung-Jen Lee, Bang-Gee Hsu
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    Guixian Zhang, Liming Tang, Hongbin Liu, Dawei Liu, Manxue Wang, Jun Cai, Weijun Liu, Wei Nie, Yi Zhang, Xiaomeng Yu
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    Hong Zhang, Zhengchao Wang
    Frontiers in Cell and Developmental Biology.2020;[Epub]     CrossRef
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    Honglian Li, Ruirui Lu, Yu Pang, Jicheng Li, Yiwen Cao, Hongxin Fu, Guoxing Fang, Qiuhe Chen, Bihao Liu, Junbiao Wu, Yuan Zhou, Jiuyao Zhou
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Review
Clinical Care/Education
Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus
Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
Diabetes Metab J. 2016;40(5):339-353.   Published online September 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.339
  • 6,451 View
  • 163 Download
  • 42 Web of Science
  • 41 Crossref
AbstractAbstract PDFPubReader   

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo), developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor. Various studies have shown that gemigliptin is an optimized DPP-4 inhibitor in terms of efficacy, safety, and patient compliance for treatment of type 2 diabetes mellitus. In this review, we summarize the characteristics of gemigliptin and discuss its potential benefits in clinical practice.

Citations

Citations to this article as recorded by  
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    Seung Hee Choi, Jaechan Leem, In-Kyu Lee
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    Chang Ho Ahn, Eun Ky Kim, Se Hee Min, Tae Jung Oh, Young Min Cho
    Diabetes, Obesity and Metabolism.2017; 19(3): 457.     CrossRef
  • Efficacy and safety of gemigliptin, a dipeptidyl peptidase‐4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24‐week, multicentre, randomized, double‐blind, placebo‐
    Chang Ho Ahn, Kyung Ah Han, Jae Myung Yu, Joo Young Nam, Kyu Jeung Ahn, Tae Keun Oh, Hyoung Woo Lee, Dae Ho Lee, Jaetaek Kim, Choon Hee Chung, Tae Sun Park, Byung Joon Kim, Seok Won Park, Hyeong Kyu Park, Kwang Jae Lee, Sang‐Wook Kim, Jeong Hyun Park, Kwa
    Diabetes, Obesity and Metabolism.2017; 19(5): 635.     CrossRef

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