Discontinued in 2013: Diabetic drugs

Expert Opinion on Investigational Drugs

Volumn 23, Issue 12, 2014, Pages 1703-1711

  Hedrington, Maka S ^a   Davis, Stephen N ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Aleglitazar; Diabetes; Diabetic nephropathy; Discontinued drugs; Fasiglifam

Indexed keywords

ALEGLITAZAR; ANTIDIABETIC AGENT; BARDOXOLONE METHYL; FASIGLIFAM; IPRAGLIFLOZIN; LY 2382770; PF 03882845; TAK 428; TZP 102; UNCLASSIFIED DRUG; NEW DRUG;

ARTICLE; DIABETES MELLITUS; DIABETIC GASTROPARESIS; DIABETIC NEPHROPATHY; DIABETIC NEUROPATHY; DRUG INDUSTRY; DRUG RECALL; HUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); ANIMAL; TREATMENT OUTCOME;

ANIMALS; DIABETES MELLITUS; DRUGS, INVESTIGATIONAL; HUMANS; HYPOGLYCEMIC AGENTS; TREATMENT OUTCOME;

EID: 84924345858     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2014.964859     Document Type: Article

References (64)

1. Nissen SE, Wolski K, Topol EJ. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 2005;294(20):2581-6
2. AstraZeneca Discontinues Development of GALIDA TM (tesaglitazar). AstraZeneca. Available from: http://www. astrazeneca.com/Media/Press-releases/Article/20060504-AstraZeneca-Discontinues-Development-of-GALIDA-TM-te [Last accessed 24 July 2014]
3. Rubenstrunk A, Hanf R, Hum DW, et al. Safety issues and prospects for future generations of PPAR modulators. Biochim Biophys Acta 2007;1771(8):1065-81
4. Matschinsky FM. Assessing the potential of glucokinase activators in diabetes therapy. Nat Rev Drug Discov 2009;8(5):399-416
5. Matschinsky FM, Zelent B, Doliba NM, et al. Research and development of glucokinase activators for diabetes therapy: theoretical and practical aspects. Handb Exp Pharmacol 2011(203):357-401; Review
6. Ohyama S, Takano H, Iino T, et al. A small-molecule glucokinase activator lowers blood glucose in the sulfonylurea-desensitized rat. Eur J Pharmacol 2010;640(1-3):250-6
7. Bonadonna RC, Heise T, Arbet-Engels C, et al. Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J Clin Endocrinol Metab 2010;95(11):5028-36
8. Verspohl EJ. Novel pharmacological approaches to the treatment of type 2 diabetes. Pharmacol Rev 2012;64(2):188-237
9. Gude D. Red carpeting the newer antidiabetics. J Pharmacol Pharmacother 2012;3(2):127-31
10. Sarabu R, Bizzarro FT, Corbett WL, et al. Discovery of piragliatin-first glucokinase activator studied in type 2 diabetic patients. J Med Chem 2012;55(16):7021-36
11. Meininger GE, Scott R, Alba M, et al. Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes. Diabetes Care 2011;34(12):2560-6
12. Development activities. Takeda. Available from: http://www.takeda.com/research/files/pipeline-20140205-en.pdf [Last accessed 24 July 2014]
13. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368(9548):1696-705; Review
14. Inagaki N, Onouchi H, Sano H, et al. SYR-472, a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2014;2(2):125-32
15. Takeda information. Takeda. Available from: https://www.takeda.com/investorinformation/files/qr2013-full-d-01-en. pdf [Last accessed 24 July 2014]
16. Veltkamp SA, Kadokura T, Krauwinkel WJ, Smulders RA. Effect of Ipragliflozin (ASP1941), a novel selective sodium-dependent glucose co-transporter 2 inhibitor, on urinary glucose excretion in healthy subjects. Clin Drug Investig 2011;31(12):839-51
17. Schwartz SL, Akinlade B, Klasen S, et al. Safety, pharmacokinetic, and pharmacodynamic profiles of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium-dependent glucose co-transporter 2, in patients with type 2 diabetes mellitus. Diabetes Technol Ther 2011;13(12):1219-27
18. Veltkamp SA, van Dijk J, Collins C, et al. Combination treatment with ipragliflozin and metformin: a randomized, double-blind, placebocontrolled study in patients with type 2 diabetes mellitus. Clin Ther 2012;34(8):1761-71
19. Zhang W, Krauwinkel WJ, Keirns J, et al. The effect of moderate hepatic impairment on the pharmacokinetics of ipragliflozin, a novel sodium glucose cotransporter 2 (SGLT2) inhibitor. Clin Drug Investig 2013;33(7):489-96
20. Annual report 2013. Astellas. Available from: https://www.astellas.com/en/ir/ library/pdf/astellas-ar2013-e-all-web.pdf [Last accessed 24 July 2014]
21. Wang H, Yu M, Ochani M, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003;421(6921):384-8
22. Pavlov VA, Ochani M, Gallowitsch-Puerta M, et al. Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA 2006;103(13):5219-23
23. Bencherif M, Lippiello PM, Lucas R, Marrero MB. Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases. Cell Mol Life Sci 2011;68(6):931-49
24. Marrero MB, Lucas R, Salet C, et al. An alpha7 nicotinic acetylcholine receptorselective agonist reduces weight gain and metabolic changes in a mouse model of diabetes. J Pharmacol Exp Ther 2010;332(1):173-80
25. Targacept discontinues two clinical trials, reports success with a third. Craver R, Available from: http://www.journalnow.com/business/article-6fda73b9-c328-5762-af1d-5d711156beec.html?mode=jqm [Last accessed 6 August 2014]
26. Bénardeau A, Benz J, Binggeli A, et al. Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. Bioorg Med Chem Lett 2009;19(9):2468-73
27. Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005;54(8):2460-70
28. Sanwald-Ducray P, Liogier D'ardhuy X, Jamois C, Banken L. Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: results from a randomized, placebo-controlled clinical study. Clin Pharmacol Ther 2010;88(2):197-203
29. Henry RR, Lincoff AM, Mudaliar S, et al. Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 2009;374(9684):126-35
30. Nicholls SJ, Lincoff AM, Henry RR, et al. Aleglitazar, a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, produces a shift towards less atherogenic LDL profile in patients with type 2 diabetes (Abstract). Eur Heart J 2010;31:1020
31. Lincoff AM, Tardif JC, Schwartz GG, AleCardio Investigators. Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial. JAMA 2014;311(15):1515-25
32. Roche halts investigation of aleglitazar following regular safety review of phase III trial. Roche. Available from: http://www.roche.com/media/media-releases/med-cor-2013-07-10.htm [Last accessed 24 July 2014]
33. Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 2003;422(6928):173-6
34. Negoro N, Sasaki S, Mikami S, et al. Discovery of TAK-875: a potent, selective, and orally bioavailable GPR40 agonist. ACS Med Chem Lett 2010;1(6):290-4
35. Tsujihata Y, Ito R, Suzuki M, et al. TAK-875, an orally available G protein-coupled receptor 40/free fatty acid receptor 1 agonist, enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats. J Pharmacol Exp Ther 2011;339(1):228-37
36. Naik H, Vakilynejad M, Wu J, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of the GPR40 agonist TAK-875: results from a double-blind, placebo-controlled single oral dose rising study in healthy volunteers. J Clin Pharmacol 2012;52(7):1007-16
37. Leifke E, Naik H, Wu J, et al. A multiple-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of a novel GPR40 agonist, TAK-875, in subjects with type 2 diabetes. Clin Pharmacol Ther 2012;92(1):29-39
38. Burant CF, Viswanathan P, Marcinak J, et al. TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 2012;379(9824):1403-11
39. Kaku K, Araki T, Yoshinaka R. Randomized, double-blind, dose-ranging study of TAK-875, a novel GPR40 agonist, in Japanese patients with inadequately controlled type 2 diabetes. Diabetes Care 2013;36(2):245-50
40. Day JW, Ottaway N, Patterson JT, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol 2009;5(10):749-57
41. Pfizer pipeline. Pfizer. Available from: http://www.pfizer.com/sites/default/files/product-pipeline/BT-February%2028,%202014%20Pipeline%20Update-28Feb14.pdf [Last accessed 24 July 2014]
42. Pfizer pipeline. Pfizer. Available from:http://www.pfizer.com/sites/default/files/product-pipeline/pipeline-2013-0509.pdf [Last accessed 24 July 2014]
43. Annual report. Piramal Enterprises Ltd. Available from: http://piramal.com/sites/default/files/PEL-Annual-Report-FY2013. pdf [Last accessed 24 July 2014]
44. Orena S, Maurer TS, She L, et al. PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy. Front Pharmacol 2013;4:115
45. Apfel SC. Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med 1999;107:2B:34S-42S; Review
46. Hellweg R, Hartung HD. Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. J Neurosci Res 1990;26(2):258-67
47. Hellweg R, Raivich G, Hartung HD, et al. Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy. Exp Neurol 1994;130(1):24-30
48. Fujinami A, Ohta K, Obayashi H, et al. Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: relationship to glucose metabolism and biomarkers of insulin resistance. Clin Biochem 2008;41(10-11):812-17
49. Krabbe KS, Nielsen AR, Krogh-Madsen R, et al. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 2007;50(2):431-8
50. Rojas-Rivera J, Ortiz A, Egido J. Antioxidants in kidney diseases: the impact of bardoxolone methyl. Int J Nephrol 2012;2012:321714
51. Ahmad R, Raina D, Meyer C, et al. Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179. J Biol Chem 2006;281(47):35764-9
52. Lisk C, McCord J, Bose S, et al. Nrf2 activation: a potential strategy for the prevention of acute mountain sickness. Free Radic Biol Med 2013;63:264-73
53. Aminzadeh MA, Reisman SA, Vaziri ND, et al. The synthetic triterpenoid RTA dh404 (CDDOdhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease. Xenobiotica 2014;44(6):570-8
54. Pergola PE, Raskin P, Toto RD, BEAM Study Investigators. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011;365(4):327-36
55. de Zeeuw D, Akizawa T, Audhya P, BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med 2013;369(26):2492-503
56. Chin MP, Reisman SA, Bakris GL, et al. Mechanisms contributing to. adverse cardiovascular events in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl. Am J Nephrol 2014;39(6):499-508
57. Kyowa Hakko Kirin announces the development status of bardoxolone methyl (RTA 402) in patients with chronic kidney disease and type 2 diabetes in Japan. Kyowa Hakko Kirin. Available from: http://www.kyowakirin.com/news-releases/2013/e20131111-01.html [Last accessed 24 July 2014]
58. Reeves WB, Andreoli TE. Transforming growth factor beta contributes to progressive diabetic nephropathy. Proc Natl Acad Sci USA 2000;97(14):7667-9
59. Sharma K, Jin Y, Guo J, Ziyadeh FN. Neutralization of TGF-beta by anti-TGF-beta antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice. Diabetes 1996;45(4):522-30
60. Chen S, Iglesias-de la Cruz MC, Jim B, et al. Reversibility of established diabetic glomerulopathy by anti-TGF-beta antibodies in db/db mice. Biochem Biophys Res Commun 2003;300(1):16-22
61. Clinical development pipeline. Eli Lilly. Available from: http://www.lilly.com/SiteCollectionDocuments/Pipeline/Clinical%20Development%20Pipeline/8.html [Last accessed 24 July 2014]
62. Ejskjaer N, Wo JM, Esfandyari T, et al. A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil 2013;25(2):e140-50
63. Morgan S, Grootendorst P, Lexchin J, et al. The cost of drug development: a systematic review. Health Policy 2011;100(1):4-17
64. The cost of diabetes. The American Diabetes Association. Available from: http://www.diabetes.org/advocacy/newsevents/cost-of-diabetes.html [Last accessed 7 September 2014]