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      KCI등재 SCOPUS SCIE

      Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus

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      https://www.riss.kr/link?id=A103551214

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      다국어 초록 (Multilingual Abstract)

      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 gl...

      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.

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      참고문헌 (Reference)

      1 Bosi E, "Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus" 11 : 506-515, 2009

      2 Dejager S, "Vildagliptin in drugnaïve patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study" 39 : 218-223, 2007

      3 Filippatos TD, "The pharmacokinetic considerations and adverse effects of DPP-4 inhibitors [corrected]" 10 : 787-812, 2014

      4 DeFronzo RA, "The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone" 32 : 1649-1655, 2009

      5 Moon JY, "The dose-dependent organ-specific effects of a dipeptidyl peptidase-4 inhibitor on cardiovascular complications in a model of type 2 diabetes" 11 : e0150745-, 2016

      6 Hwang HJ, "The dipeptidyl peptidase-IV inhibitor inhibits the expression of vascular adhesion molecules and inflammatory cytokines in HUVECs via Akt- and AMPK-dependent mechanisms." 405 : 25-34, 2015

      7 Morishita R, "Teneligliptin: expectations for its pleiotropic action" 16 : 417-426, 2015

      8 American Diabetes Association., "Standards of medical care in diabetes: 2014" 37 (37): S14-S80, 2014

      9 Jadzinsky M, "Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy:a randomized controlled trial" 11 : 611-622, 2009

      10 Taskinen MR, "Safety and efficacy of linagliptin as addon therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study" 13 : 65-74, 2011

      1 Bosi E, "Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus" 11 : 506-515, 2009

      2 Dejager S, "Vildagliptin in drugnaïve patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study" 39 : 218-223, 2007

      3 Filippatos TD, "The pharmacokinetic considerations and adverse effects of DPP-4 inhibitors [corrected]" 10 : 787-812, 2014

      4 DeFronzo RA, "The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone" 32 : 1649-1655, 2009

      5 Moon JY, "The dose-dependent organ-specific effects of a dipeptidyl peptidase-4 inhibitor on cardiovascular complications in a model of type 2 diabetes" 11 : e0150745-, 2016

      6 Hwang HJ, "The dipeptidyl peptidase-IV inhibitor inhibits the expression of vascular adhesion molecules and inflammatory cytokines in HUVECs via Akt- and AMPK-dependent mechanisms." 405 : 25-34, 2015

      7 Morishita R, "Teneligliptin: expectations for its pleiotropic action" 16 : 417-426, 2015

      8 American Diabetes Association., "Standards of medical care in diabetes: 2014" 37 (37): S14-S80, 2014

      9 Jadzinsky M, "Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy:a randomized controlled trial" 11 : 611-622, 2009

      10 Taskinen MR, "Safety and efficacy of linagliptin as addon therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study" 13 : 65-74, 2011

      11 정권수, "Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice" 대한당뇨병학회 40 (40): 211-221, 2016

      12 Rizzo MR, "Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition" 35 : 2076-2082, 2012

      13 Omar B, "Pleiotropic mechanisms for the glucoselowering action of DPP-4 inhibitors" 63 : 2196-2202, 2014

      14 Aroor AR, "Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system" 307 : H477-H492, 2014

      15 Baetta R, "Pharmacology of dipeptidyl peptidase-4inhibitors: similarities and differences" 71 : 1441-1467, 2011

      16 Kim SH, "Pharmacological profiles of gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivo" 788 : 54-64, 2016

      17 Lim KS, "Pharmacokinetics, pharmacodynamics, and tolerability of the dipeptidyl peptidase IV inhibitor LC15-0444 in healthy Korean men: a dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, phase I study" 30 : 1817-1830, 2008

      18 Lim KS, "Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers" 68 : 883-890, 2009

      19 Shin D, "Pharmacokinetic and pharmacodynamic interaction between gemigliptin and metformin in healthy subjects" 34 : 383-393, 2014

      20 Yoon S, "No. 804: Efficacy and safety of gemigliptin in type 2 diabetes patients with moderate to severe renal impairment" 2015

      21 Lee BW, "No. 803: Effects of gemigliptin versus sitagliptin or glimepiride on glycaemic variability as initial combination therapy with metformin in drugnaïve patients with type 2 diabetes" 2015

      22 Yoon S, "No. 1199:Efficacy and safety of gemigliptin in type 2 diabetes patients with moderate to severe renal impairment" 2016

      23 Kim SH, "No. 1169: Efficacy and safety of gemigliptin as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin and glimepiride" 2016

      24 Rhee EJ, "No. 1128: Efficacy and safety of gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone" 2012

      25 Rhee EJ, "No. 111: Gemigliptin added to ongoing metformin therapy provides sustained glycemic control over 52 weeks and was well tolerated in patients with type 2 diabetes" 2013

      26 Lim S, "No. 109: Efficacy and safety of gemigliptin/metformin initial combination therapy versus either as monotherapy in drug-naïve patients with type 2 diabetes" 2015

      27 Cho YM, "New clinical experience of gemigliptin, the new DPPIV inhibitor" 2012

      28 Zemiglo, "Ministry of Food and Drug Safety (MFDS) Package insert"

      29 Inzucchi SE, "Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)" 35 : 1364-1379, 2012

      30 Barnett AH, "Linagliptin monotherapy in type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III trial with a 34-week active-controlled extension" 14 : 1145-1154, 2012

      31 Haak T, "Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, doubleblind, placebo-controlled study" 14 : 565-574, 2012

      32 Rosenstock J, "Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes" 10 : 376-386, 2008

      33 Jung E, "Gemigliptin, a novel dipeptidyl peptidase-4 inhibitor, exhibits potent anti-glycation properties in vitro and in vivo" 744 : 98-102, 2014

      34 Sung-Ho Kim, "Gemigliptin, a novel dipeptidyl peptidase 4 inhibitor: first new anti-diabetic drug in the history of Korean pharmaceutical industry" 대한약학회 36 (36): 1185-1188, 2013

      35 Jung E, "Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy" 1852 : 2618-2629, 2015

      36 Jung E, "Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy" 761 : 116-124, 2015

      37 Kothny W, "Gallwitz B, Lukashevich V. Improved glycaemic control with vildagliptin added to insulin, with or without metformin, in patients with type 2 diabetes mellitus" 15 : 252-257, 2013

      38 Choi HY, "Evaluation of the pharmacokinetics of the DPP-4 inhibitor gemigliptin when coadministered with rosuvastatin or irbesartan to healthy subjects" 31 : 229-241, 2015

      39 Kim SE, "Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase IV inhibitor LC15-0444 and pioglitazone in healthy volunteers" 50 : 17-23, 2012

      40 Choi HY, "Evaluation of pharmacokinetic drug interactions between gemigliptin (dipeptidylpeptidase-4 inhibitor) and glimepiride (sulfonylurea) in healthy volunteers" 14 : 165-176, 2014

      41 Kadowaki T, "Efficacy, safety and dose-response relationship of teneligliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus" 15 : 810-818, 2013

      42 Pi-Sunyer FX, "Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes" 76 : 132-138, 2007

      43 Lukashevich V, "Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea" 16 : 403-409, 2014

      44 Hermansen K, "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin" 9 : 733-745, 2007

      45 Raz I, "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus" 49 : 2564-2571, 2006

      46 Charbonnel B, "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone" 29 : 2638-2643, 2006

      47 Rhee EJ, "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone" 15 : 523-530, 2013

      48 DeFronzo RA, "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study" 31 : 2315-2317, 2008

      49 Hong S, "Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus:a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial" 18 : 528-532, 2016

      50 Kim MK, "Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trial" 17 : 309-312, 2015

      51 Vilsboll T, "Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes" 12 : 167-177, 2010

      52 Owens DR, "Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea:a 24-week randomized study" 28 : 1352-1361, 2011

      53 Duran-Garcia S, "Efficacy and safety of linagliptin as add-on therapy to basal insulin and metformin in people with Type 2 diabetes" 33 : 926-933, 2016

      54 Pratley RE, "Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes:a randomized, double-blind, 6-month study" 16 : 613-621, 2014

      55 Nauck MA, "Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, doubleblind, placebo-controlled study" 63 : 46-55, 2009

      56 Marfella R, "Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations" 24 : 79-83, 2010

      57 Bosi E, "Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin" 30 : 890-895, 2007

      58 Noh YH, "Effects of ketoconazole and rifampicin on the pharmacokinetics of gemigliptin, a dipeptidyl peptidase-IV inhibitor:a crossover drug-drug interaction study in healthy male Korean volunteers" 34 : 1182-1194, 2012

      59 Choi HY, "Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500mg x 2 tablets) fixeddose combination tablet in healthy male volunteers" 52 : 381-391, 2014

      60 Aschner P, "Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes" 29 : 2632-2637, 2006

      61 Rosenstock J, "Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes" 25 : 2401-2411, 2009

      62 Barnett AH, "Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin" 28 : 513-523, 2012

      63 Shon JH, "Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15-0444)." 16 : 1028-1031, 2014

      64 Del Prato S, "Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial" 13 : 258-267, 2011

      65 Goldstein BJ, "Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes" 30 : 1979-1987, 2007

      66 Hwang HJ, "Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes" 392 : 1-7, 2014

      67 Deacon CF, "Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review" 13 : 7-18, 2011

      68 Choi SH, "Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation." 73 : 11-19, 2015

      69 Min HS, "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction" 94 : 598-607, 2014

      70 Garber AJ, "Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm: 2016 executive summary" 22 : 84-113, 2016

      71 Deacon CF, "Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas" 18 : 333-347, 2016

      72 Rosenstock J, "Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia" 11 : 1145-1152, 2009

      73 Kim N, "Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans" 44 : 522-530, 2014

      74 Kim Y, "Absorption, distribution, metabolism and excretion of gemigliptin, a novel dipeptidyl peptidase IV inhibitor, in rats" 44 : 627-634, 2014

      75 Moses RG, "A randomized controlled trial ofthe efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea" 16 : 443-450, 2014

      76 Yang SJ, "A multicentre, multinational, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in patients with type 2 diabetes" 15 : 410-416, 2013

      77 Rhee EJ, "A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes" 12 : 1113-1119, 2010

      78 Nabeno M, "A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site" 434 : 191-196, 2013

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