Novel GLP-1 receptor agonists for diabetes

Expert Opinion on Investigational Drugs

Volumn 21, Issue 1, 2012, Pages 45-57

  Garber, Alan J ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Albiglutide; Exenatide; GLP 1; GLP 1 receptor agonist; Liraglutide; Lixisenatide; Taspoglutide; Type 2 diabetes mellitus

Indexed keywords

ALBIGLUTIDE; EXENDIN 4; GLIMEPIRIDE; GLIMEPIRIDE PLUS METFORMIN; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR STIMULATING AGENT; GLUCOSE; GLYCOSYLATED HEMOGLOBIN; HORMONE RECEPTOR STIMULATING AGENT; INSULIN; INSULIN GLARGINE; LIRAGLUTIDE; LIXISENATIDE; METFORMIN; METFORMIN PLUS ROSIGLITAZONE; PIOGLITAZONE; SITAGLIPTIN; SULFONYLUREA; TASPOGLUTIDE; UNCLASSIFIED DRUG;

BLINDNESS; CARDIOVASCULAR DISEASE; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DIABETIC NEUROPATHY; DIABETIC RETINOPATHY; DIARRHEA; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; GLYCEMIC CONTROL; HUMAN; HYPERTENSION; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN TREATMENT; KIDNEY FAILURE; LIMB AMPUTATION; MICROANGIOPATHY; MONOTHERAPY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS ISLET ALPHA CELL; PANCREAS ISLET BETA CELL; PATIENT COMPLIANCE; RETINOPATHY; REVIEW; SINGLE DRUG DOSE; WEIGHT REDUCTION;

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DRUG APPROVAL; HOMEOSTASIS; HUMANS; HYPOGLYCEMIC AGENTS; RECEPTORS, GLUCAGON;

EID: 84555191794     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.638282     Document Type: Review

References (93)

1. World Health Organization. Obesity and overweight. Available from: http://www whoint/mediacentre/factsheets/fs311/en/index html,2010 [Last accessed 21 December 2010]
2. Department of health and Human Services. Centers for Disease Control and Prevention. National Diabetes Fact Sheet. Available from: http://www cdc gov/diabetes/pubs/pdf/ndfs-2007 pdf,2007 [Last accessed 12 January 2011]
3. Fox CS, Pencina MJ, Meigs JB, et al. Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study. Circulation 2006;113:2914-18 (Pubitemid 44297232)
4. National Institutes of Health. National Diabetes Statistics, 2007. Available from: http://www diabetes niddk nih gov/dm/pubs/statistics/index htm,2010 [Last accessed 21 December 2010]
5. Girard J. The incretins: from the concept to their use in the treatment of type 2 diabetes. Part A: incretins: concept and physiological functions. Diabetes Metab 2008;34:550-9.
6. American Diabetes Association. Standards of Medical Care in Diabetes-2008. Diabetes Care 2008;31:S12-54
7. Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest 2007;117:24-32 (Pubitemid 46048446)
8. Brubaker PL, Anini Y. Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol 2003;81:1005-12 (Pubitemid 38045829)
9. Hansen L, Lampert S, Mineo H, Holst JJ. Neural regulation of glucagon-like peptide-1 secretion in pigs. Am J Physiol Endocrinol Metab 2004;287:E939-47 (Pubitemid 39382931)
10. Vahl TP, Drazen DL, Seeley RJ, et al. Meal-anticipatory glucagon-like peptide-1 secretion in rats. Endocrinology 2010;151:569-75
11. Tolhurst G, Reimann F, Gribble FM. Nutritional regulation of glucagon-like peptide-1 secretion. J Physiol 2009;587:27-32
12. Buteau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival. Diabetes Metab 2008;34(Suppl 2):S73-7 (Pubitemid 351978286)
13. Drucker DJ. Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 2003;17:161-71 (Pubitemid 36183142)
14. Aaboe K, Krarup T, Madsbad S, Holst JJ. GLP-1: physiological effects and potential therapeutic applications. Diabetes Obes Metab 2008;10:994-1003.
15. Holst JJ, Deacon CF, Vilsboll T, et al. Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol Med 2008;14:161-8
16. Pannacciulli N, Bunt JC, Koska J, et al. Higher fasting plasma concentrations of glucagon-like peptide 1 are associated with higher resting energy expenditure and fat oxidation rates in humans. Am J Clin Nutr 2006;84:556-60 (Pubitemid 44713405)
17. Grieve DJ, Cassidy RS, Green BD. Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control? Br J Pharmacol 2009;157:1340-51
18. Nikolaidis LA, Mankad S, Sokos GG, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004;109:962-5 (Pubitemid 38282847)
19. Sokos GG, Nikolaidis LA, Mankad S, et al. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 2006;12:694-9 (Pubitemid 44881367)
20. 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
21. Holst JJ, Burcelin R, Nathanson E. Neuroprotective properties of GLP-1: theoretical and practical applications. Curr Med Res Opin 2011;27:547-58
22. Vaag A. On the pathophysiology of late onset non-insulin dependent diabetes mellitus. Current controversies and new insights. Dan Med Bull 1999;46:197-234 (Pubitemid 29300651)
23. Vilsboll T, Holst JJ, Knop FK. The spectrum of antidiabetic actions of GLP-1 in patients with diabetes. Best Pract Res Clin Endocrinol Metab 2009;23:453-62
24. Christensen M, Knop FK. Once-weekly GLP-1 agonists: How do they differ from exenatide and liraglutide? Curr Diab Rep 2010;10:124-32
25. 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.
26. Garg SK. The role of basal insulin and glucagon-like peptide-1 agonists in the therapeutic management of type 2 diabetes-a comprehensive review. Diabetes Technol Ther 2010;12:11-24
27. Penfornis A, Borot S, Raccah D. Therapeutic approach of type 2 diabetes mellitus with GLP-1 based therapies. Diabetes Metab 2008;34(Suppl 2):S78-90 (Pubitemid 351978287)
28. Davidson JA. Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Cleve Clin J Med 2009;76(Suppl 5):S28-38
29. Behme MT, Dupre J, McDonald TJ. Glucagon-like peptide 1 improved glycemic control in type 1 diabetes. BMC Endocr Disord 2003;3:3
30. Dupre J, Behme MT, McDonald TJ. Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab 2004;89:3469-73 (Pubitemid 38951922)
31. Rother KI, Spain LM, Wesley RA, et al. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care 2009;32:2251-7
32. Drucker DJ, Sherman SI, Bergenstal RM, Buse JB. The safety of incretin-based therapies-review of the scientific evidence. J Clin Endocrinol Metab 2011;96:2027-31
33. Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem 1997;272:4108-15 (Pubitemid 27078475)
34. Byetta Summary of Product Characteristics. Available from: http://www ema europa eu/docs/en-GB/document-library/EPAR-Product-Information/human/000698/ WC500051845 pdf,2010 [Last accessed 16 December 10 A.D]
35. 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)
36. 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)
37. 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)
38. Barnett AH, Burger J, Johns D, et al. Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther 2007;29:2333-48 (Pubitemid 350298125)
39. Heine RJ, Van Gaal LF, Johns D, et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2005;143:559-69
40. Nauck MA, Duran S, Kim D, et al. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 2007;50:259-67
41. Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008;24:275-86 (Pubitemid 351160260)
42. Buse JB, Bergenstal RM, Glass LC, et al. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med 2011;154:103-12
43. DeFronzo RA, Okerson T, Viswanathan P, et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin 2008;24:2943-52
44. Mikhail N. Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of type 2 diabetes. Expert Opin Investig Drugs 2008;17:845-53 (Pubitemid 351864322)
45. Bradley DP, Kulstad R, Schoeller DA. Exenatide and weight loss. Nutrition 2010;26:243-9
46. Malone J, Trautmann M, Wilhelm K, et al. Exenatide once weekly for the treatment of type 2 diabetes. Expert Opin Investig Drugs 2009;18:359-67
47. Kim D, MacConell L, Zhuang D, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 2007;30:1487-93 (Pubitemid 46871159)
48. European Medicines Agency. EMA Assessment Report for Bydureon; 2011
49. 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.
50. 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;96:1301-10.
51. 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.
52. Wysham C, Bergenstal R, Malloy J, et al. DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide. Diabet Med 2011;28:705-14.
53. Diamant M, Van GL, 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.
54. Buse JB, Nauck M, Forst T, et al. Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomised, open-label study. Presented at the European Association for the Study of Diabetes (EASD), 12-16 September 2011 Abstract No. 75. Key Phase III trial with exenatide once weekly.
55. Eli Lilly. DURATION-6 Top-Line Study Results Announced. 2011
56. Deyoung MB, MacConell L, Sarin V, et al. Encapsulation of Exenatide in Poly-(d,l-Lactide-Co-Glycolide) Microspheres Produced an Investigational Long-Acting Once-Weekly Formulation for Type 2 Diabetes. Diabetes Technol Ther 2011;published online; doi:10.1089/dia.2011.0050 [doi]
57. Food and Drug Administration. Guidance for Industry. E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. Available from: http://www fda gov/downloads/ RegulatoryInformation/Guidances/ucm129357 pdf,2005 [Last accessed 6 January 11 A.D]
58. Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000;43:1664-9 (Pubitemid 30304999)
59. Knudsen LB. Glucagon-like peptide-1: the basis of a new class of treatment for type 2 diabetes. J Med Chem 2004;47:4128-34 (Pubitemid 39045416)
60. Madsen K, Knudsen LB, Agersoe H, et al. Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: importance of fatty acid length, polarity, and bulkiness. J Med Chem 2007;50:6126-32
61. Victoza Summary of product characteristics. Available from: http://www ema europa eu/docs/en-GB/document-library/EPAR-Product-Information/human/001026/ WC500050017 pdf,2010 [Last accessed 15 December 2010]
62. Drab SR. Clinical studies of liraglutide, a novel, once-daily human glucagon-like peptide-1 analog for improved management of type 2 diabetes mellitus. Pharmacotherapy 2009;29:43S-54S.
63. 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.
64. 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.
65. 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.
66. 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.
67. 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.
68. 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.
69. Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther 2009;31:2472-88
70. Neumiller JJ, Campbell RK. Liraglutide: a once-daily incretin mimetic for the treatment of type 2 diabetes mellitus. Ann Pharmacother 2009;43:1433-44
71. 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
72. 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. Diabet Med 2010;27:1024-32.
73. Christensen M, Knop FK, Vilsboll T. The GetGoal clinical trial program of lixisenatide, a once-daily GLP-1 receptor agonist. Expert Rev Endocrinol Metab 2011;6:513-25
74. Sanofi-aventis. Once-Daily Lixisenatide in Combination with Basal Insulin Demonstrates Significant Improvement in Glucose Control. Available from: http://en sanofi-aventis com/binaries/20100930-GETGOAL-en-tcm28-29296 pdf,2010 [Last accessed 7 January 2011]
75. ClinicalTrials.gov. www clinicaltrials gov, 2010. Available from: www.clinicaltrials. gov [Last accessed 29 November 2010]
76. Zealand Pharma A/S. Zealand Pharma Announces An Extension of The Lixisenatide Global Licensing Agreement with sanofi-aventis for Type-2 Diabetes. Available from: http://www marketwire com/press-release/Zealand-Pharma- Announces-An-Extension-The-Lixisenatide-Global-Licensing-Agreementwith-1272421 htm,2010 [Last accessed 7 January 2011]
77. 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
78. 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
79. 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.
80. 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
81. Tomkin GH. Albiglutide, an albumin-based fusion of glucagon-like peptide 1 for the potential treatment of type 2 diabetes. Curr Opin Mol Ther 2009;11:579-88
82. Retterstol K. Taspoglutide: a long acting human glucagon-like polypeptide-1 analogue. Expert Opin Investig Drugs 2009;18:1405-11
83. Kapitza C, Heise T, Birman P, et al. Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once-weekly, human GLP-1 analogue, after single-dose administration in patients with Type 2 diabetes. Diabet Med 2009;26:1156-64
84. Nauck MA, Ratner RE, Kapitza C, et al. Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care 2009;32:1237-43.
85. Ratner R, Nauck M, Kapitza C, et al. Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study. Diabet Med 2010;27:556-62
86. Dennis M. Roche stops dosing patients in late-stage taspoglutide studies. Available from: http://www firstwordplus com/Fws do?articleid=1BE3E9330CB840 FEBFFED2DFB527ED71,2010 Available from: http://www.firstwordplus. com/Fws.do?articleid=1BE3E9330CB840 FEBFFED2DFB527ED71 [Last accessed 22 August 2011]
87. Torsoli A. Roche said to return diabetes drug rights to Ipsen. Bloomberg. Available from: http://www.businessweek com/news/2011-02-01/roche-said- toreturn-diabetes-drug-rights-to-ipsen html,2011
88. Bell DS. A comparison of agents used to manage type 2 diabetes mellitus: need for reappraisal of traditional approaches. Treat Endocrinol 2004;3:67-76 (Pubitemid 38337557)
89. Maedler K, Carr RD, Bosco D, et al. Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab 2005;90:501-6 (Pubitemid 40116700)
90. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009;15:540-59
91. Knowler WC, Fowler SE, Hamman RF, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009;374:1677-86
92. Bode BW, Testa MA, Magwire M, et al. Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab 2010;12:604-12
93. Wajchenberg BL. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev 2007;28:187-218 (Pubitemid 46984834)