Emerging GLP-1 receptor agonists

Expert Opinion on Emerging Drugs

Volumn 16, Issue 4, 2011, Pages 607-618

  Lund, Asger ^a   Knop, Filip K ^a   Vilsbøll, Tina ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Albiglutide; CJC 1134 PC; Dulaglutide; Exenatide; Exenatide once weekly; Glucagon like peptide 1 receptor agonists; Liraglutide; Lixisenatide; Semaglutide; Type 2 diabetes

Indexed keywords

ALBIGLUTIDE; ANTIDIABETIC AGENT; CJC 1134PC; DIPEPTIDYL PEPTIDASE IV INHIBITOR; DULAGLUTIDE; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; HEMOGLOBIN A1C; INCRETIN; INSULIN; INSULIN GLARGINE; LIRAGLUTIDE; LIXISENATIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METFORMIN; PLACEBO; SEMAGLUTIDE; SITAGLIPTIN; SULFONYLUREA; UNCLASSIFIED DRUG;

ACUTE PANCREATITIS; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MARKETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; GASTROINTESTINAL SYMPTOM; GLYCEMIC CONTROL; HEART INFARCTION; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERSENSITIVITY; HYPOGLYCEMIA; IN VIVO STUDY; INJECTION SITE ERYTHEMA; INJECTION SITE INDURATION; INJECTION SITE PAIN; INJECTION SITE PRURITUS; KIDNEY DISEASE; LIFE EXPECTANCY; META ANALYSIS (TOPIC); NAUSEA; NAUSEA AND VOMITING; NEUROPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PHASE 3 CLINICAL TRIAL (TOPIC); QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RETINOPATHY; REVIEW; SEDENTARY LIFESTYLE; SIDE EFFECT; STROKE; SYSTOLIC BLOOD PRESSURE; WEIGHT GAIN; WEIGHT REDUCTION;

CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; DRUGS, INVESTIGATIONAL; GLUCAGON-LIKE PEPTIDE 1; HUMANS; HYPOGLYCEMIC AGENTS; PEPTIDES; RECEPTORS, GLUCAGON; TREATMENT OUTCOME; VENOMS;

EID: 84555191763     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2011.616493     Document Type: Review

References (93)

1. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87:1409-39 (Pubitemid 350041474)
2. Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 2007;113:546-93 (Pubitemid 46365961)
3. Kjems LL, Holst JJ, Vølund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003;52:380-6 (Pubitemid 36173193)
4. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 7-36 amide but ot of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301-7 (Pubitemid 23037285)
5. Vilsboll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia 2002;45:1111-19 (Pubitemid 34985287)
6. Holz GG. Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes 2004;53:5-13 (Pubitemid 38044691)
7. Renstrom E, Eliasson L, Rorsman P. Protein kinase A-dependent and-independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol (Lond) 1997;502(Pt 1):105-18 (Pubitemid 27322979)
8. Shibasaki T, Takahashi H, Miki T, et al. Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc Natl Acad Sci USA 2007;104:19333-8
9. Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999;48:2270-6 (Pubitemid 30395416)
10. Stoffers DA, Kieffer TJ, Hussain MA, et al. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 2000;49:741-8 (Pubitemid 30339989)
11. Zhou J, Wang X, Pineyro MA, Egan JM. Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon-and insulin-producing cells. Diabetes 1999;48:2358-66 (Pubitemid 30395427)
12. Buteau J, El-Assaad W, Rhodes CJ, et al. Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia 2004;47:806-15 (Pubitemid 38756992)
13. Larsson H, Holst JJ, Ahren B. Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol Scand 1997;160:413-22 (Pubitemid 27342031)
14. Willms B, Werner J, Holst JJ, et al. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 1996;81:327-32
15. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998;101:515-20 (Pubitemid 28084232)
16. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulp://www.ema. europa.eu/ema/index.jspin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-30
17. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995;80:952-7
18. Vilsboll T, Agerso H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003;88:220-4 (Pubitemid 36115169)
19. Zhang P, Zhang X, Brown J, et al. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87:293-301
20. Farag YMK, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant 2011;26:28-35
21. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-53
22. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89
23. Gakidou E, Mallinger L, Abbott-Klafter J, et al. Management of diabetes and associated cardiovascular risk factors in seven countries: a comparison of data from national health examination surveys. Bull World Health Organ 2011;89:172-83
24. Carver C. Insulin treatment and the problem of weight gain in type 2 diabetes. Diabetes Educ 2006;32:910-17 (Pubitemid 44706818)
25. Korytkowski M. When oral agents fail: practical barriers to starting insulin. Int J Obes Relat Metab Disord 2002;26(SUPPL. 3):S18-24 (Pubitemid 35034478)
26. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med 2010;123:S12-18
27. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65
28. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006;29:1963-72 (Pubitemid 44156663)
29. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203
30. Riddle MC. Therapy: what evidence should guide the use of thiazolidinediones? Nat Rev Endocrinol 2010;6:600-2
31. Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol 2009;5:262-9
32. Eng J, Kleinman WA, Singh L, et al. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992;267:7402-5
33. Linnebjerg H, Kothare PA, Park S, et al. Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol 2007;64:317-27 (Pubitemid 47283860)
34. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39-47
35. Buse JB, Henry RR, Han J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628-35 (Pubitemid 39441462)
36. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083-91 (Pubitemid 40616617)
37. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092-100 (Pubitemid 40616618)
38. Madsbad S, Krarup T, Deacon CF, Holst JJ. Glucagon-like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials. Curr Opin Clin Nutr Metab Care 2008;11:491-9
39. Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens 2010;23:334-9
40. Best JH, Hoogwerf BJ, Herman WH, et al. Risk of cardiovascular disease events in patients with type 2 diabetes rescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care 2011;34:90-5
41. Neumiller JJ, Sonnett TE, Wood LD, et al. Pharmacology, efficacy and safety of liraglutide in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2010;3:215-26
42. Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)-preclinical and clinical results. Best Pract Res Clin Endocrinol Metab 2009;23:463-77
43. Joffe D. Liraglutide: a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes mellitus. Am J Health Syst Pharm 2010;67:1326-36
44. Marre M, Shaw J, Brandle M, et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med 2009;26:268-78
45. Russell-Jones D, Vaag A, Schmitz O, et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met +SU): a randomised controlled trial. Diabetologia 2009;52:2046-55
46. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009;373:473-81
47. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39-47
48. Zinman B, Gerich J, Buse JB, et al. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care 2009;32:1224-30
49. Nauck M, Frid A, Hermansen K, et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009;32:84-90
50. Buse JB, Sesti G, Schmidt WE, et al. Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 diabetes using oral agents. Diabetes Care 2010;33:1300-3
51. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 2007;298:194-206 (Pubitemid 47057766)
52. Ahren B. GLP-1 for type 2 diabetes. Exp Cell Res 2011;317:1239-45 Blonde L, Russell-Jones D.
53. The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. Diabetes Obes Metab 2009;11(SUPPL. 3):26-34
54. Byetta: scientific discussion. European Medicines Agency-EPARs for authorised medicinal products for human use. Available from: http://www.ema. europa.eu/ema/index.jsp?curl=search.jsp&q=byetta%3A+scientific+discussion +&btnG=Search&murl=menus% 2Fmedicines%2Fmedicines. jsp&mid= WC0b01ac058001d125 Last accessed 13 April 2011
55. Anderson SL, Trujillo JM. Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother 2010;44:904-9
56. Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care 2009;32:834-8
57. Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like Peptide-1-based therapies. Gastroenterology 2011;141:150-6
58. Aus der UAW-Datenbank. Pankreaskarzinome im Zusammenhang mit Exenatid (Byetta®) (Aus der UAW-Datenbank). 2011. Available from: http://www.akdae.de/Arzneimittelsicherheit/Bekanntgaben/20110513.html Last accessed 1 August 2011
59. European Medicine Agency. Anti diabetic drugs: Cardio/cerebrovascular adverse effect and pancreatitis/pancreatic cancer. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=search.jsp&site= pfoi-collection&entsp=0&sort=date:D:L:d1&client=pfoi- frontend&curl=search.jsp&curl=search.jsp&btnG=Search&entqr= 0&access=p&ip=172.16.100.1&oe=UTF-8&proxyreload=1&q= GLP-1+pancreatic+cancer&ie=UTF-8&ud=1&mid=&murl=menus/ special-topics/special-topics.jsp&output=xml-no-dtd&proxystylesheet= pfoi-frontend&filter=0&filter=0&start=0 Last accessed 1 August 2011
60. FDA. Briefing materials: liraglutide. Available from: http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4422b2-01-FDA.pdf Last accessed 12 April 2011
61. Bjerre Knudsen L, Madsen LW, Andersen S, et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010;151:1473-86
62. Rosenstock J, Reusch J, Bush M, et al. Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care 2009;32:1880-6
63. Verspohl EJ. Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther 2009;124:113-38
64. Bergenstal RM, Wysham C, Macconell L, et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 2010;376:431-9
65. Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 2010;375:2234-43
66. Amylin Pharmaceuticals, Inc. PressRelease: duration-4 study results: Bydureon Efficacy and Tolerability Extended to Monotherapy Treatment. Available from: http://phx.corporate-ir. net/phoenix.zhtml?c=101911&p=irol- newsArticle&ID=1438147&highlight= Last accessed 8 April 2011
67. Blevins T, Pullman J, Malloy J, et al. DURATION-5: exenatide once weekly resulted in greater improvements in Glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab 2011;Available from: http://www.ncbi. nlm.nih.gov/pubmed/21307137 Last accessed 28 March 2011
68. Amylin Pharmaceuticals, Inc. PressRelease: Duration-6 Top-Line Study Results Announced. Available from: http://phx.corporate-ir.net/phoenix.zhtml?c= 101911&p=irol-newsArticle&ID=1535419&highlight=Last accessed 8 April 2011
69. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008;372:1240-50
70. Buse JB, Drucker DJ, Taylor KL, et al. DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care 2010;33:1255-61
71. Bruce S, Han J, Brown C, et al. Safety and tolerability of exenatide once weekly pooled summary of 1095 patients from DURATION-1, 2, and 3. Diabetes 2010;59:A16-17
72. Linnebjerg H, Seger M, Kothare P, et al. The effect of exonatide on QTc interval in healthy subjects. Diabetes 2009;58:A161-1
73. Idris I. FDA Request further studies on the once weekly exenatide, bydureon. Diabetes Obes Metab 2011;13:94-4
74. Christensen M, Knop FK, Vilsboll T, Holst JJ. Lixisenatide for type 2 diabetes mellitus. Expert Opin Investig Drugs 2011;20:549-57
75. Thorkildsen C, Neve S, Larsen BD, et al. Glucagon-like peptide 1 receptor agonist ZP10A increases insulin mRNA expression and prevents diabetic progression in db/db mice. J Pharmacol Exp Ther 2003;307:490-6 (Pubitemid 37310661)
76. Distiller L, Ruus P. Pharmacokinetics and pharmacodynamics of GLP-1 agonist AVE0010 in type 2 diabetes patients. Diabetes 2008;57:A154-5
77. Liu Y, Ruus P. Pharmacokinetics and Safety of the GLP-1 Agonist AVE0010 in patients with renal impairment. Diabetes 2009;58:A149-50
78. Gerich J, Fonseca V, Alvarado-Ruiz R, et al. Monotherapy with GLP-1 receptor agonist, Lixisenatide, significantly improves glycaemic control in type 2 diabetic patients. Diabetologia 2010;53:830
79. Ratner RE, Rosenstock J, Boka G. Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial. Diabetes Med 2010;27:1024-32
80. Christensen M, Knop FK, Holst JJ, Vilsboll T. Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. IDrugs 2009;12:503-13
81. Sanofi-Aventis. Press-Release: Sanofi-Aventis Announces positive top-line lixisenatide phase III results. Available from: http://en.sanofi-aventis.com/ press/press-releases/2011/news-list-2011.asp Last accessed 8 April 2011
82. Baggio LL, Huang Q, Cao X, Drucker DJ. An albumin-exendin-4 conjugate engages central and peripheral circuits regulating murine energy and glucose homeostasis. Gastroenterology 2008;134:1137-47 (Pubitemid 351451971)
83. Wang M, Kipnes M, Matheson S, et al. Safety and pharmacodynamics of CJC-1134-PC, a novel GLP-1 receptor agonist, in patients with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blind, dose-escalation study. Diabetes 2007;56:A133-3
84. Wang M, Matheson S, Picard J, et al. PC-DAC (TM): Exendin-4 (CJC-1134-PC) significantly reduces hba1c and body weight as an adjunct therapy to metformin: Two randomized, double-blind, placebo-controlled, 12 week, phase ii studies in patients with type 2 diabetes mellitus. Diabetes 2009;58:A148-8
85. St Onge EL, Miller SA. Albiglutide: a new GLP-1 analog for the treatment of type 2 diabetes. Expert Opin Biol Ther 2010;10:801-6
86. Bush MA, Matthews JE, De Boever EH, et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in healthy subjects. Diabetes Obes Metab 2009;11:498-505
87. Matthews JE, Stewart MW, De Boever EH, et al. Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in patients with type 2 diabetes. J Clin Endocrinol Metab 2008;93:4810-17
88. Seino Y, Nakajima H, Miyahara H, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of albiglutide, a long-acting GLP-1-receptor agonist, in Japanese subjects with type 2 diabetes mellitus. Curr Med Res Opin 2009;25:3049-57
89. Glaesner W, Vick AM, Millican R, et al. Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev 2010;26:287-96
90. Barrington P, Chien JY, Showalter HDH, et al. A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analog, in patients with type 2 diabetes. Diabetes Obes Metab 2011;Available from: http://www.ncbi.nlm.nih.gov/pubmed/21251178 Last accessed 1 Februar 2011
91. Barrington P, Chien JY, Tibaldi F, et al. LY2189265, a long-acting glucagon like-peptide-1 analog, demonstrated dose-dependent insulin secretion in healthy subjects. Diabetes Obes Metab 2011;13:343-438
92. Umpierrez GE, Blevins T, Rosenstock J, et al. The effects of LY2189265, a long-acting glucagon-like peptide-1 analog, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: the EGO study. Diabetes Obes Metab 2011;Available from: http://www.ncbi. nlm.nih.gov/pubmed/21251180 Last accessed 1 February 2011
93. Schernthaner G, Barnett AH, Betteridge DJ, et al. Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. Diabetologia 2010;53:1258-69