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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/01/23 01:54:12」(JST)

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Vildagliptin (previously LAF237, trade names Galvus, Zomelis,) is an oral anti-hyperglycemic agent (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1^[2]^[3] and GIP^[3] by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas.

Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus.^[2]

Combination with metformin

The EMEA has also approved a new oral treatment released by Novartis, called Eucreas, a combination of vildagliptin and metformin.^[4]

Adverse Effects

Adverse effects observed in clinical trials include nausea, hypoglycemia, tremor, headache and dizziness. Rare cases of hepatoxicity have been reported.^[5]

There have been case reports of pancreatitis associated with DPP-IV inhibitors. A group at UCLA reported increased pre-cancerous pancreatic changes in rats and in human organ donors who had been treated with DPP-IV inhibitors.^[6]^[7] In response to these reports, the United States FDA and the European Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-IV inhibitors with pancreatic cancer. In a joint letter to the New England Journal of Medicines, the agencies stated that "Both agencies agree that assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and in the media, are inconsistent with the current data. The FDA and the EMA have not reached a final conclusion at this time regarding such a causal relationship. Although the totality of the data that have been reviewed provides reassurance, pancreatitis will continue to be considered a risk associated with these drugs until more data are available; both agencies continue to investigate this safety signal."^[8]

References

^ WHO International Working Group for Drug Statistics Methodology (August 27, 2008). "ATC/DDD Classification (FINAL): New ATC 5th level codes". WHO Collaborating Centre for Drug Statistics Methodology. Retrieved 2008-09-05.
^ ^a ^b Ahrén, B; Landin-Olsson, M; Jansson, PA; Svensson, M; Holmes, D; Schweizer, A (2004). "Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes". The Journal of Clinical Endocrinology and Metabolism. 89 (5): 2078–84. doi:10.1210/jc.2003-031907. PMID 15126524.
^ ^a ^b Mentlein, R; Gallwitz, B; Schmidt, WE (1993). "Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum". European Journal of Biochemistry / FEBS. 214 (3): 829–35. doi:10.1111/j.1432-1033.1993.tb17986.x. PMID 8100523.
^ EU approves Novartis's Eucreas diabetes drug. Reuters, February 25, 2008.
^ "www.ema.europa.eu" (PDF).
^ Matveyenko AV, Dry S, Cox HI, et al. (July 2009). "Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin". Diabetes. 58 (7): 1604–15. doi:10.2337/db09-0058. PMC 2699878. PMID 19403868.
^ Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC (July 2013). "Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors". Diabetes. 62 (7): 2595–604. doi:10.2337/db12-1686. PMC 3712065. PMID 23524641.
^ Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; De Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis (2014). "Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment — NEJM". New England Journal of Medicine. 370 (9): 794–7. doi:10.1056/NEJMp1314078. PMID 24571751.

External links

Banting and Best Diabetes Centre at UT vildagliptin – Vildagliptin
Banting and Best Diabetes Centre at UT dpp4 – About DPP-4
The race to get DPP-4 inhibitors to market – Forbes.com
Merck's March Madness – Forbes.com

UpToDate Contents

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1. 2型糖尿病の治療のためのジペプチジルペプチダーゼ4（DPP-4）阻害剤 dipeptidyl peptidase 4 dpp 4 inhibitors for the treatment of type 2 diabetes mellitus
2. 透析前慢性腎臓病または末期腎不全を伴う2型糖尿病患者における高血糖のマネージメント management of hyperglycemia in patients with type 2 diabetes and pre dialysis chronic kidney disease or end stage renal disease
3. 2型糖尿病治療のためのGlucagon-like peptide-1受容体拮抗剤 glucagon like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus
4. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus
5. 胃不全麻痺の治療 treatment of gastroparesis

English Journal

Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial.

Lukashevich V, Schweizer A, Shao Q, Groop PH, Kothny W.SourceNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA Novartis Pharma AG, Basel, Switzerland Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland Folkhalsan Institute of Genetics, Folkhalsan Research Center, Biomedicum Helsinki of Helsinki, Finland.
Diabetes, obesity & metabolism.Diabetes Obes Metab.2011 Oct;13(10):947-54. doi: 10.1111/j.1463-1326.2011.01467.x.
Aim: Assess safety/tolerability and efficacy of the DPP-4 inhibitor vildagliptin in 515 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI). Methods: Double-blind, randomized, parallel-group, placebo-controlled, 24-week clinical trial assessing safety and effic
PMID 21733061

Linagliptin: A Novel Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor for Treatment of Type II Diabetes Mellitus.

Ghatak SB, Patel DS, Shanker N, Srivastava A, Deshpande SS, Panchal SJ.SourceDepartment of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad-382 481, Gujarat, India. ghataksom16@gmail.com.
Current diabetes reviews.Curr Diabetes Rev.2011 Sep 15. [Epub ahead of print]
Type 2 diabetes mellitus causes significant morbidity and mortality on account of its progressive nature and results in considerable burden on healthcare resources. Current treatment strategies have only limited long-term efficacy and tolerability given the progressive nature of the disease leading
PMID 21916836

Japanese Journal

最新の論文紹介持続血糖モニター(CGM)によるDPP-4阻害薬ビルダグリプチンとシタグリプチン投与時における血糖変動の比較 : クロスオーバー試験による検討

坂本昌也
Life style medicine : journal of life style medicine 7(2), 125-128, 2013-02
NAID 40019560692

Pancreatitis with Pancreatic Tail Swelling Associated with Incretin-based Therapies Detected Radiologically in Two Cases of Diabetic Patients with End-Stage Renal Disease

Nakata Hirosuke,Sugitani Seita,Yamaji Shuhei,Otsu Satoko,Higashi Yoshihito,Ohtomo Yumiko,Inoue Gen
Internal Medicine 51(21), 3045-3049, 2012
… A 75-year-old woman with a history of liraglutide use and a 68-year-old man with a history of vildagliptin use both presented with nausea. …
NAID 130002061953

Related Pictures

Description Vildagliptin synthesis.png : Galvus 50mg, Content: Vildagliptin File:Vildagliptin Structural Formulae.png vildagliptin tablets vildagliptin tablets what is vildagliptin vildagliptin is an of vildagliptin chemical name vildagliptin Medication: VILDAGLIPTIN–METFORMIN Description Vildagliptin-3D-balls.png

★リンクテーブル★

リンク元	「ビルダグリプチン」

「ビルダグリプチン」

Vildagliptin
Clinical data
Trade names	Galvus
AHFS/Drugs.com	International Drug Names
License data	EU EMA: Galvus;
Pregnancy; category	Not recommended;
Routes of; administration	Oral
ATC code	A10BH02 (WHO); A10BD08 (WHO) (with metformin)
Legal status
Legal status	UK: POM (Prescription only);
Pharmacokinetic data
Bioavailability	85%
Protein binding	9.3%
Metabolism	Mainly hydrolysis to inactive metabolite; CYP450 not appreciably involved
Biological half-life	2 to 3 hours
Excretion	Renal
Identifiers
	IUPAC name (S)-1-[N-(3-hydroxy-1-adamantyl)glycyl]pyrrolidine-2-carbonitrile;
Synonyms	(2S)-1-{2-[(3-hydroxy-1-adamantyl)amino]acetyl}pyrrolidine-2-carbonitrile
CAS Number	274901-16-5
PubChem (CID)	6918537
IUPHAR/BPS	6310
DrugBank	DB04876
ChemSpider	5293734
UNII	I6B4B2U96P
KEGG	D07080
ChEMBL	CHEMBL142703
ECHA InfoCard	100.158.712
Chemical and physical data
Formula	C17H25N3O2
Molar mass	303.399 g/mol
3D model (Jmol)	Interactive image
	SMILES N#C[C@H]4N(C(=O)CNC13CC2CC(C1)CC(O)(C2)C3)CCC4 ;
	InChI InChI=1S/C17H25N3O2/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16/h12-14,19,22H,1-8,10-11H2/t12?,13?,14-,16?,17?/m0/s1 ; Key:SYOKIDBDQMKNDQ-XWTIBIIYSA-N ;
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　　[★]

英: vildagliptin
商: エクア(ノバルティスファーマ)
関: 経口血糖降下薬、DPP-4阻害薬

用量

通常は、ビルダグリプチンとして50mgを1日2回朝、夕
中等度以上の腎機能障害・透析中の末期腎不全の例では50mgを1日1回朝

処方例

エクア

(健常人)ビルダグリプチン50mg 1回1錠 1日2回　朝夕
(減量例)ビルダグリプチン50mg 1回1錠 1日1回　朝

[1] WHO International Working Group for Drug Statistics Methodology (August 27, 2008). "ATC/DDD Classification (FINAL): New ATC 5th level codes". WHO Collaborating Centre for Drug Statistics Methodology. Retrieved 2008-09-05.

[ahren-2] Ahrén, B; Landin-Olsson, M; Jansson, PA; Svensson, M; Holmes, D; Schweizer, A (2004). "Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes". The Journal of Clinical Endocrinology and Metabolism. 89 (5): 2078–84. doi:10.1210/jc.2003-031907. PMID 15126524.

[mentlein-3] Mentlein, R; Gallwitz, B; Schmidt, WE (1993). "Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum". European Journal of Biochemistry / FEBS. 214 (3): 829–35. doi:10.1111/j.1432-1033.1993.tb17986.x. PMID 8100523.

[reuters_eucreas-4] EU approves Novartis's Eucreas diabetes drug. Reuters, February 25, 2008.

[5] "www.ema.europa.eu" (PDF).

[6] Matveyenko AV, Dry S, Cox HI, et al. (July 2009). "Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin". Diabetes. 58 (7): 1604–15. doi:10.2337/db09-0058. PMC 2699878. PMID 19403868.

[7] Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC (July 2013). "Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors". Diabetes. 62 (7): 2595–604. doi:10.2337/db12-1686. PMC 3712065. PMID 23524641.

[8] Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; De Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis (2014). "Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment — NEJM". New England Journal of Medicine. 370 (9): 794–7. doi:10.1056/NEJMp1314078. PMID 24571751.

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vildagliptin