Discovery and development of exenatide: the first antidiabetic agent to leverage the multiple benefits of the incretin hormone, GLP-1

Bibliography

• Centers for Disease Control and Prevention. Diabetes Data and Trends 2011; Diabetes Fact Sheet 2011. Available from: http://apps.nccd.cdc.gov/DDTSTRS
   Google Scholar
• American Diabetes Association. Standards of medical care in diabetes-2012. Diabetes Care 2012;35:S11-63
   PubMed Web of Science ®Google Scholar
• Kotronen A, Yki-Järvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008;28:27-38
   PubMed Web of Science ®Google Scholar
• DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58:773-95
   PubMed Web of Science ®Google Scholar
• Göke R, Fehmann HC, Linn T, Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)- amide receptor of insulin-secreting β-cells. Biol Chem 1993;268:19650-5
   Web of Science ®Google Scholar
• Byrne MM, Göke B. Lessons from human studies with glucagon-like peptide-1: potential of the gut hormone for clinical use. In: Fehmann HC, Göke B, editors. Insulinotropic gut hormone glucagon-like peptide 1. Karger; Basel, New York: 1997. p. 219-33
   Google Scholar
• Wettergren A, Schjoldager B, Mortensen PE, Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Digest Dis Sci 1993;38:665-73
   PubMed Web of Science ®Google Scholar
• Creutzfeldt WOC, Orskov C, Kleine N, Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients. Diabetes Care 1996;19:580-6
   PubMed Web of Science ®Google Scholar
• Turton MD, O'Shea D, Gunn I, A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996;379:69-72
   PubMed Web of Science ®Google Scholar
• Elrick H, Stimmler L, Hlad CJ, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab 1964;24:1076-82
   PubMed Web of Science ®Google Scholar
• Holst JJ, Vilsbøll T, Deacon CF. The incretin system and its role in type 2 diabetes. Mol Cell Endocrinol 2009;297:127-36
   PubMed Web of Science ®Google Scholar
• Nauck MA, Heimesaat MM, Ørskov C, Preserved incretin activity of glucagon-like peptide 1[7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301-7
   PubMed Web of Science ®Google Scholar
• Nauck MA, Wollschläger D, Werner J, Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia 1996;39:1546-53
   PubMed Web of Science ®Google Scholar
• Nauck MA, Niedereich-Holz U, Ettler R, Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997;273:E981-8
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Flint A, Raben A, Ersbøll AK, The effects of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int J Obes 2001;25:781-92
   PubMed Web of Science ®Google Scholar
• Näslund E, Barkeling B, King N, Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes 1999;23:304-11
   PubMed Web of Science ®Google Scholar
• Thorens B. Physiology of GLP-1-lessons from glucoincretin receptor knockout mice. Horm Metab Res 2004;36:766-70
   PubMed Web of Science ®Google Scholar
• Young AA. Glucagon-like peptide-1, exendin and insulin sensitivity. In: Hansen B, Shafrir E, editors. Insulin resistance and insulin resistance syndrome. Harwood Academic; New York: 2002. p. 235-62
   Google Scholar
• Edvell A, Linström P. Initiation of increased pancreatic islet growth in young normoglycemic mice (Umeå +/?). Endocrin 1999;140:778-83
   PubMed Web of Science ®Google Scholar
• Stoffers DA, Kieffer TJ, Hussain MA, 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
   PubMed Web of Science ®Google Scholar
• Farilla L, Hui H, Bertolotto C, Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrin 2002;143:4397-408
   PubMed Web of Science ®Google Scholar
• Baggio L, Drucker DJ. Therapeutic approaches to preserve islet mass in type 2 diabetes. Annu Rev Med 2006;57:265-81
   PubMed Web of Science ®Google Scholar
• Wang YH, Perfetti R, Greig NH, Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats. J Clin Invest 1997;99:2883-9
   PubMed Web of Science ®Google Scholar
• Deacon CF, Nauck MA, Toft-Nielsen M, Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126-31
   PubMed Web of Science ®Google Scholar
• Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide-1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinol 1995;136:3585-96
   PubMed Web of Science ®Google Scholar
• Raufman JP, Singh L, Singh G, Eng J. Truncated glucagon-like peptide-1 interacts with exendin receptors on dispersed acini from guinea pig pancreas. Identification of a mammalian analogue of the reptilian peptide exendin-4. J Biol Chem 1992;267:21432-7
   PubMed Web of Science ®Google Scholar
• Thorens B. Expression cloning of the pancreatic β-cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA 1992;89:8641-5
   PubMed Web of Science ®Google Scholar
• Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors Channels 2002;8:179-88
   PubMedGoogle Scholar
• Nielsen LL, Young AA, Parkes DG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Reg Pept 2004;117:77-88
   PubMed Web of Science ®Google Scholar
• Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology 1996;137:2968-78
   PubMed Web of Science ®Google Scholar
• Ban K, Noyan-Ashraf MH, Hoefer J, Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide-1 receptor dependent and independent pathways. Circulation 2008;117:2340-50
   PubMed Web of Science ®Google Scholar
• Meloni AR, DeYoung MB, Lowe C, Parkes DG. GLP-1 receptor activated insulin secretion from pancreatic beta-cells: mechanism and glucose-dependence. Diab Obes Metab 2012; doi: 10.1111/j.1463-1326.2012.01663.x
   PubMed Web of Science ®Google Scholar
• Scrocchi LA, Brown TJ, MaClusky N, Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide receptor gene. Nat Med 1996;2:1254-8
   PubMed Web of Science ®Google Scholar
• Flamez D, Van Breusegem A, Scrocchi LA, Mouse pancreatic β-cells exhibit preserved glucose competence after disruption of the glucagon-like peptide-1 receptor gene. Diabetes 1998;47:646-52
   PubMed Web of Science ®Google Scholar
• Pederson RA, Satkunarajah M, McIntosh CH, Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide-1 receptor -/- mice. Diabetes 1998;47:1046-52
   PubMed Web of Science ®Google Scholar
• Scrocchi LA, Marshall BA, Cook SM, Identification of glucagon-like peptide 1 (GLP-1) actions essential for glucose homeostasis in mice with disruption of GLP-1 receptor signaling. Diabetes 1998;47:632-9
   PubMed Web of Science ®Google Scholar
• Scrocchi LA, Drucker DJ. Effects of aging and a high fat diet on body weight and glucose tolerance in glucagon-like peptide-1 receptor -/- mice. Endocrinol 1998;139:3127-32
   PubMed Web of Science ®Google Scholar
• Flamez D, Gilon P, Moens K, Altered cAMP and Ca2+ signaling in mouse pancreatic islets with glucagon-like peptide-1 receptor null phenotype. Diabetes 1999;48:1979-86
   PubMed Web of Science ®Google Scholar
• Burcelin R, Da Costa A, Drucker D, Thorens B. Glucose competence of the heptoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes 2001;50:1720-8
   PubMed Web of Science ®Google Scholar
• De Leon DD, Deng S, Madani R, Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy. Diabetes 2003;52:365-71
   PubMed Web of Science ®Google Scholar
• Eng J, Kleinman WA, Singh L, 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
   PubMed Web of Science ®Google Scholar
• Freeman JS. Role of the incretin pathway in the pathogenesis of type 2 diabetes mellitus. Cleve Clin J Med 2009;76(Suppl 5):S12-19
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Thorens B, Porret A, Buühler L, Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor. Diabetes 1993;42:1678-82
   PubMed Web of Science ®Google Scholar
• Raufman JP. Bioactive peptides from lizard venoms. Regul Pept 1996;61:1-18
   PubMed Web of Science ®Google Scholar
• Fehmann HC, Jiang J, Schweinfurth J, Stable expression of the rat GLP-I receptor in CHO cells: activation and binding characteristics utilizing GLP-I(7-36)-amide, oxyntomodulin, exendin-4, and exendin(9-39). Peptides 1994;15:453-6
   PubMed Web of Science ®Google Scholar
• Schepp W, Schmidtler J, Riedel T, Exendin-4 and exendin-(9-39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide-1-(7-36)NH2. Eur J Pharmacol 1994;269:183-91
   PubMed Web of Science ®Google Scholar
• Montrose-Rafizadeh C, Yang H, Wang Y, Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3-L1 adipocytes. J Cell Physiol 1997;172:275-83
   PubMed Web of Science ®Google Scholar
• Nishizawa M, Nakabayashi H, Kawai K, The hepatic vagal reception of intraportal GLP-1 is via receptor different from the pancreatic GLP-1 receptor. J Auton Nerv Syst 2000;80:14-21
   PubMedGoogle Scholar
• Yang H, Egan JM, Wang Y, GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor. Am J Physiol 1998;273:C675-83
   Google Scholar
• Young AA, Gedulin BR, Bhavsar S, Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes 1999;48:1026-34
   PubMed Web of Science ®Google Scholar
• Szayna M, Doyle ME, Betkey JA, Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000;141:1936-41
   PubMed Web of Science ®Google Scholar
• Parkes DG, Pittner R, Jodka C, Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro. Metabolism 2001;50:583-9
   PubMed Web of Science ®Google Scholar
• Egan JM, Clocquet AR, Elahi D. The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. J Clin Endocrinol Metab 2002;87:1282-90
   PubMed Web of Science ®Google Scholar
• Greig NH, Holloway HW, De Ore KA, Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia 1999;42:45-50
   PubMed Web of Science ®Google Scholar
• Gedulin B, Jodka C, Hoyt J. Exendin-4 (AC2993) decreased glucagon secretion during hyperglycemic clamps in Diabetic Fatty Zucker rats [abstract 0864]. Diabetes 1999;48(Suppl 1):A199
   Google Scholar
• Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care 2001;24:371-81
   PubMed Web of Science ®Google Scholar
• Mack CM, Moore CX, Jodka CM, Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures. Int J Obes (Lond) 2006;30:1332-40
   PubMed Web of Science ®Google Scholar
• Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999;48:2270-6
   PubMed Web of Science ®Google Scholar
• Tourrel C, Bailbé D, Meile M-J, Glucagon-like peptide-1 and exendin-4 stimulate β-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 2001;50:1562-70
   PubMed Web of Science ®Google Scholar
• Tourrel C, Bailbé D, Lacorne M, Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the β-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4. Diabetes 2002;51:1443-52
   PubMed Web of Science ®Google Scholar
• Gedulin BR, Nikoulina SE, Smith PA, Exenatide (exendin-4) improves insulin sensitivity and β-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology 2005;146:2069-76
   PubMed Web of Science ®Google Scholar
• Parkes D, Jodka C, Smith P, Pharmacokinetic actions of exendin-4 in the rat: comparison with glucagon-like peptide-1. Drug Dev Res 2001;53:260-7
   Web of Science ®Google Scholar
• Eng J. Prolonged effect of exendin-4 on hyperglycemia of db/db mice [abstract 554]. Diabetes 1996;45:152A
   Web of Science ®Google Scholar
• Ahren B, Pacini G. Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess β-cell function in clinical studies. Eur J Endocrinol 2004;150:97-104
   PubMed Web of Science ®Google Scholar
• Parkes D, Gedulin B, Smith P, Young A. Effect of exendin-4 on glucagon secretion in lean and obese Zucker (ZDF) rats [abstract 1298-P]. Diabetes 2001;50(Suppl 2):A313
   Google Scholar
• Stoffers DA, Desai BM, DeLeon DD, Simmons RA. Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat. Diabetes 2003;52:734-40
   PubMed Web of Science ®Google Scholar
• Rolin B, Larsen MO, Gotfredsen CF, The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases β-cell mass in diabetic mice. Am J Physiol Endocriol Metab 2002;283:E745-52
   PubMed Web of Science ®Google Scholar
• Wang Q, Brubaker PL. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 2002;45:1263-73
   PubMed Web of Science ®Google Scholar
• Li Y, Hansotia T, Yusta B, Glucagon-like peptide-1 receptor signaling modulates cell apoptosis. J Biol Chem 2003;278:471-8
   PubMed Web of Science ®Google Scholar
• Jodka C, Gedulin B, Young A. Exendin-4 potently regulates gastric emptying in rats [abstract 1543]. Diabetes 1998;47(Suppl 1):A403
   Google Scholar
• Dickson SL, Shirazi RH, Hansson C, The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors. J Neurosci 2012;32:4812-20
   PubMed Web of Science ®Google Scholar
• Kinzig KP, D'Alessio DA, Seeley RJ. The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness. J Neurosci 2002;22:10470-6
   PubMed Web of Science ®Google Scholar
• Egan JM, Montrose-Rafizadeh C, Want Y, Glucagon-like peptide-1(7-36) amide (GLP-1) enhances insulin-stimulated glucose metabolism in 3T3-L1 adipocytes: one of several potential extrapancreatic sites of GLP-1 action. Endocrinology 1994;135:2070-5
   PubMed Web of Science ®Google Scholar
• Wang Y, Kole HK, Montrose-Rafizadeh C, Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes: glucagon-like peptide-1 and insulin interactions. J Molec Endocrinol 1997;19:241-8
   PubMed Web of Science ®Google Scholar
• Laugero KD, Stonehouse AH, Guss S, Exenatide improves hypertension in a rat model of the metabolic syndrome. Metab Syndr Relat Disord 2009;7:327-34
   PubMed Web of Science ®Google Scholar
• Hirata K, Kume S, Araki S, Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochem Biophys Res Commun 2009;380:44-9
   PubMed Web of Science ®Google Scholar
• Liu Q, Adams L, Broyde A, The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats. Cardiovasc Diabetol 2010;9:32
   PubMed Web of Science ®Google Scholar
• Timmers L, Henriques JPS, de Kleijn DPV, Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 2009;53:501-10
   PubMed Web of Science ®Google Scholar
• Liu Q, Anderson C, Broyde A, Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure. Cardiovasc Diabetol 2010;9:76
   PubMed Web of Science ®Google Scholar
• Arakawa M, Mita T, Azuma K, Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes 2010;59:1030-7
   PubMed Web of Science ®Google Scholar
• Hsieh J, Longuet C, Baker CL, The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice. Diabetologia 2010;53:552-61
   PubMed Web of Science ®Google Scholar
• Harkavyi A, Whitton PS. Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection. Br J Pharmacol 2010;159:495-501
   PubMed Web of Science ®Google Scholar
• Perry T, Lahiri DK, Chen D, A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells. J Pharmacol Exp Ther 2002;300:958-66
   PubMed Web of Science ®Google Scholar
• Perry T, Haughey NJ, Mattson MP, Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther 2002;302:881-8
   PubMed Web of Science ®Google Scholar
• Perry T, Holloway HW, Weerasuriya A, Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 2007;203:293-301
   PubMed Web of Science ®Google Scholar
• Li Y, Perry T, Kindy MS, GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci USA 2009;106:1285-90
   PubMed Web of Science ®Google Scholar
• Li Y, Chigurupati S, Holloway HW, Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis. PLoS ONE 2012;7:e32008
   PubMed Web of Science ®Google Scholar
• Byrd R, Flanagan S, Kothare P, Pharmacokinetics of exenatide long acting release (LAR) in monkeys. Presented at the 2006 annual meeting of the Amer Assoc Pharm Sci 2006
   Google Scholar
• Copley K, McCowen K, Hiles R, Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab 2006;7:367-74
   PubMed Web of Science ®Google Scholar
• Gao W, Jusko WJ. Target-mediated pharmacokinetic and pharmacodynamic model of exendin-4 in rats, monkeys, and humans. Drug Metab Dispos 2012;40:990-7
   PubMed Web of Science ®Google Scholar
• Hiles RA, Bawdon RE, Petrella EM. Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4). Human Exper Toxicol 2003;22:623-8
   PubMed Web of Science ®Google Scholar
• Tatarkiewicz K, Smith PA, Sablan EJ, Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents. Am J Physiol Endocrinol Metab 2010;299:E1076-86
   PubMed Web of Science ®Google Scholar
• Nachnani JS, Bulchandani DG, Nookala A, Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas. Diabetologia 2010;53:153-9
   PubMed Web of Science ®Google Scholar
• Koehler JA, Baggio LL, Lamont BJ, Glucagon-like peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice. Diabetes 2009;58:2148-61
   PubMed Web of Science ®Google Scholar
• Tatarkiewicz K, Belanger P, Gu G, Long-term exposure of exenatide does not adversely affect exocrine pancreas structure and function in Zucker diabetic fatty (ZDF) rats. Diabetologia (Abstract 818-P) 2011;54(Suppl 1):185
   Web of Science ®Google Scholar
• Vrang N, Jelsing J, Simonsen L, The effects of 13 weeks of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF-rats: a quantitative and qualitative analysis revealing no evidence of drug induced pancreatitis. Am J Physiol Endocrinol Metab 2012;303:E253-64
   PubMed Web of Science ®Google Scholar
• BYETTA (exenatide) injection prescribing information. Revised December 2011. Available from: http://www.byetta.com
   Google Scholar
• BYDUREON (exenatide extended-release for injectable suspension) prescribing information. Revised January 2012. Available from: http://www.bydureon.com
   Google Scholar
• Bhavsar S, Mudaliar S, Cherrington A. Evolution of exenatide as a diabetes therapeutic. Curr Diab Rev 2012; In press
   Google Scholar
• Aroda V, Henry R, Han J, Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther 2012;34:1247-58. e22
   PubMed Web of Science ®Google Scholar
• MacConell L, Brown C, Gurney K, Han J. Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo- and comparator-controlled clinical trials. Diabetes Metab Syndr Obes 2012;5:29-41
   PubMedGoogle Scholar
• MacConell L, Gurney K, Malloy J, Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4328 patients. Diabetes 2012;61(Suppl 1):A598; 2372-PO
   Google Scholar
• Blevins T, Han J, Nicewarner D, Exenatide non-inferior to insulin in reducing HbA1c: an integrated analysis of 1423 patients with type 2 diabetes. Postgrad Med 2010;122:118-28
   PubMed Web of Science ®Google Scholar
• Buse JB, Bergenstal RM, Glass LC, 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
   PubMed Web of Science ®Google Scholar
• Klonoff DC, Buse JB, Nielsen LL, Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 2 years. Curr Med Res Opin 2008;24:275-86
   PubMed Web of Science ®Google Scholar
• DeYoung MB, MacConell L, Sarin V, 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;13:1145-54
   PubMed Web of Science ®Google Scholar
• Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care 2010;33:2349-54
   PubMed Web of Science ®Google Scholar
• Elashoff M, Matveyenko AV, Gier B, Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141:150-6
   PubMed Web of Science ®Google Scholar
• Wenton M, Gaebler JA, Hussein M, Relative risk of acute pancreatitis in initiators of exenatide twice daily compared with other antidiabetic medication: a follow-up study. Diabet Med 2012;29:1412-18
   PubMed Web of Science ®Google Scholar
• Linnebjerg H, Kothare PA, Park S, Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol 2007;64:317-27
   PubMed Web of Science ®Google Scholar
• Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hyperten 2010;23:334-9
   PubMed Web of Science ®Google Scholar
• Lønborg J, Vejlstrup N, Kelbæk H, Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J 2012;33:1491-9
   PubMed Web of Science ®Google Scholar
• Lønborg J, Kelbæk H, Vejlstrup N, Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ Cardiovasc Interv 2012;5:288-95
   PubMed Web of Science ®Google Scholar
• Gejl M, Søndergaard HM, Stecher C, Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. J Clin Endocrinol Metab 2012;97:E1165-9
   PubMed Web of Science ®Google Scholar
• Nathanson D, Ullman B, Löfström U, Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: a double-blind, randomised controlled clinical trial of efficacy and safety. Diabetologia 2012;55:926-35
   PubMed Web of Science ®Google Scholar
• Dupré J, Behme MT, McDonald TJ. Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab 2004;89:3469-73
   PubMed Web of Science ®Google Scholar
• Varanasi A, Bellini N, Rawal D, Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol 2011;165:77-84
   PubMed Web of Science ®Google Scholar
• Kielgast U, Krarup T, Holst JJ, Madsbad S. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual β-cell function. Diabetes Care 2011;34:1463-8
   PubMed Web of Science ®Google Scholar
• VICTOZA liraglutide (rDNA origin) injection prescribing information. Revised April 2012. Available from: http://www.victoza.com
   Google Scholar
• Buse JB, Rosenstock J, Sesti G, 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
   PubMed Web of Science ®Google Scholar
• Buse JB, Nauck MA, Forst T, Exenatide once weekly versus liraglutide in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 2012; In press
   Web of Science ®Google Scholar
• Best JH, Lavillotti K, DeYoung MB, Garrison LP. The effects of exenatide bid on metabolic control, medication use and hospitalization in patients with type 2 diabetes mellitus in clinical practive: a systematic review. Diab Obes Metab 2012;14:387-98
   PubMed Web of Science ®Google Scholar
• Anderson SL, Trujillo JM. Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother 2010;44:904-9
   PubMed Web of Science ®Google Scholar
• Dore DD, Seeger JD, Chan KA. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared with metformin or glyburide. Curr Med Res Opin 2009;25:1019-27
   PubMed Web of Science ®Google Scholar
• Dore DD, Bloomgren GL, Wenten M, A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab 2011;13:559-66
   PubMed Web of Science ®Google Scholar
• Raufman JP, Jensen RT, Sutliff VE, Actions of Gila monster venom on dispersed acini from guinea pig pancreas. Am J Physiol 1982;242:G470-4
   PubMed Web of Science ®Google Scholar
• Navarro M, Rodriguez de Fonseca F, Alvarez E, Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neurochem 1996;67:1982-91
   PubMed Web of Science ®Google Scholar
• Rodriquez de Fonseca F, Navarro M, Alvarez E, Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats. Metabolism 2000;49:709-17
   PubMed Web of Science ®Google Scholar
• Thum A, Hupe-Sodmann K, Göke R, Endoproteolysis by isolated membrane peptidases reveal metabolic stability of glucagon-like peptide-1 analogs, exendins-3 and -4. Exp Clin Endocrinol Diabetes 2002;110:113-18
   PubMed Web of Science ®Google Scholar
• Gedulin BR, Smith P, Prickett KS, Dose-response for glycaemic and metabolic changes 28 days after single injection of long-acting release exenatide in diabetic fatty Zucker rats. Diabetologia 2005;48:1380-5
   PubMed Web of Science ®Google Scholar
• Ding X, Saxena NK, Lin S, Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 2006;43:173-81
   PubMed Web of Science ®Google Scholar
• Simonsen L, Holst JJ, Deacon CF. Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular filtration in anaesthetised pigs. Diabetologia 2006;49:706-12
   PubMed Web of Science ®Google Scholar
• Gedulin BR, Smith P, Jodka CM, Pharmacokinetics and pharmacodynamics of exenatide following alternate routes of administration. Int J Pharm 2008;356:231-8
   PubMed Web of Science ®Google Scholar
• U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 21-773 Pharmacology review. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021773_Byetta_pharmr.PDF
   Google Scholar
• U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 022200Orig1s000 Pharmacology review(s). Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/022200Orig1s000PharmR.pdf
   Google Scholar