2006, Number 6
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Gac Med Mex 2006; 142 (6)
Exenatide: Use in humans.
Sierra-Ascencio ME, Ríos-Vaca A, Reza-Albarrán A
Language: Spanish
References: 44
Page: 483-491
PDF size: 146.51 Kb.
ABSTRACT
Exenatide is the first synthetic agonist of the GLP-1 (glucagon-like peptide 1) receptor approved for clinical use in patients with type 2 diabetes. The multiplicity of its effects over glucose metabolism, appetite, body weight and its potential capacity to preserve the ?cell mass, makes it an attractive therapeutic alternative. This article attempts to review the current literature on pharmacokinetics, pharmacodynamics, efficacy, and safety of exenatide in humans, derived from the early phase I and II studies, and from the clinical controlled trials that led to its approval for clinical use as a combination therapy with sulphonylureas and metformin.
REFERENCES
Elrick H, Stimmler L, Hlad CJ, Arai Y. Plasma insulin responses to oral and intravenous glucose administration. J Clin Endocrinol Metab 1964;24:1076-1082.
Mc Intyre N, Holdsworth CD, Turner DS. Intestinal factors in the control of insulin secretion. J Clin Endocrinol Metab 1965;25:1317-1324.
Creutzfeldt W, Ebert R. New developments in the incretin concept today. Diabetologia 1985;28:565-573.
Drucker DJ. Glucagon-like peptides: regulators of cell proliferation, differentiation and apoptosis. Mol Endocrinol 2003;17:161-171.
Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 2003;26:2929-2940.
Sharma A, Zangen DH, Reitz P, Taneja M, Lissauer ME, Miller CP, et al. The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration. Diabetes 1999;48:507-513.
Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Natl Med 2000;6:278-282.
Farilla L, Bulotta A, Hirshberg B, Li Calzi S, Khoury N, Noushmehr H, et al. Glucagon like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003;141:5149-5158.
Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001;50:609-613.
Lugari R, Dei Cas A, Ugolotti D, Finardi L, Barilli AL, Ognibene C, et al. Evidence for early impairment of glucagon-like peptide-1 induced insulin secretion in human type 2 (non-insulin dependent) diabetes. Horm Metab Res 2002;34:150-154.
Matsuyama T, Komatsu R, Namba M, Watanabe N, Itoh H, Tarui S. Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone. Diabetes Res Clin Pract 1988;5:281-284.
Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Truncated GLP-1 (proglucagon 78-107 amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993;38:665-673.
Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom PM. Glucagonlike peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 1998;68:525-530.
Davis HR Jr, Mullins DE, Pines JM, Hoos LM, France CF, Compton DS, et al. Effect of chronic central administration of glucagon-like peptide-1 (7-36) amide on food consumption and body weight in normal and obese rats. Obes Res 1998;6:147-156.
Szayna M, Doyle ME, Betkey JA, Holloway HW, Spencer RG, Greig NH, et al. Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000;141:1936-1941.
Thorens B. Expression cloning of the pancreatic h-cell receptor for the glucoincretin hormone glucagon-like peptide 1. Proc Natl Acad Sci U S A 1992;89:8641-8645.
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;267:21432-21437.
Raufman JP, Singh L, Eng J. Exendin-3, a novel peptide from Heloderma horridum venom, interacts with vasoactive intestinal peptide receptors and a newly described receptor on dispersed acini from guinea pig pancreas. Description of exendin-3(9–39), a specific exendin receptor antagonist. J Biol Chem 1991;266:2897-2902.
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. Endocrinology 1995;136:3585-3596.
Mentlein R, Gallwitz B, Schmidt WE. 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. Eur J Biochem 1993;214:829-835.
Larsen J, Hylleberg B, Ng K, Damsbo P. Glucagon-like peptide-1 infusion must be maintained for 24h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment.Diabetes Care 2001;24:1416-1421.
Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin 4,an exendin 3 analogue from Heloderma suspectum venom. J Biol Chem 1992;267:740-745.
Drucker DJ. Glucagon-like peptides. Diabetes 1998;47:159-169.
Gedulin B, Jodka C, Hoyt J. Exendin-4 (AC-2993) decreases glucagons secretion during hyperglycemic clamps in diabetic fatty Zucker rats (abstract). Diabetes 1999;48:A199.
Szayna M, Doyle ME, Betkey JA, Holloway HW, Spencer RGS, Greig NH, et al. Exendin- 4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000;141:1936-1941.
Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both B cell replication and neogenesis, resulting in increased B cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999;48:2270-2276.
Young AA, Gedulin BR, Bhavsar S, Bodkin N, Jodka C, Hansen B, et al. 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;48:1026-1034.
Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman M, Baron A. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health-Syst Pharm 2005;62:173-181.
Edwards CM, Stanley SA, Davis R, Brynes AE, Frost GS, Seal LJ, et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001;281:155-161.
Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, et al. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003;88:3082-3089.
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;87:1282-1290.
Degn KB, Brock B, Juhl CB, Djurhuus CB, Grubert J, Kim D, et al. Effect of intravenous infusion of exenatide (synthetic Exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes 2004;53:2397-2403.
Blase E, Taylor K, Gao H, Wintle M, Fineman N. Pharmacokinetics of an oral drug (Acetaminophen) administered at various times in relation to subcutaneous injections of exenatide (Exendin-4) in healthy subjects. Journal of Clinical Pharmacology 2005;45:570-577.
Dupré J, Behme MT, MCDonald TJ. Exendin-4 Normalized Postcibal Glycemic Excursions in Type 1 Diabetes. J Clin Endocrinol Metab 2004;89:3469-3473.
Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylureatreated patients with type 2 diabetes mellitus. Diabetes Care 2004;27:2628-2635.
Kim D, Zhang B, Mac S, Poon T, Fineman M. Exenatide (Exendin-4) Reduced Mean A1C and Weight over 82 Weeks in Sulfonylurea-Treated Patients with Type 2 Diabetes (Abstract). Presented at the 87th Annual Meeting of The Endocrine Society’s, San Diego, CA, June 4-7, 2005. Poster 3-405.
De Fronzo R, Ratner R, Han J, Kim D, Fineman M, Baron A. Glycemic Control and Weight Over 30 Weeks in Metformin-Treated Patients With Type 2 Diabetes. Diabetes Care 2005;28:1092-1100.
Kim D, Stonehouse A, Han J, Bicsak T, Kolterman O, Taylor K. Exenatide (Exendin-4) Reduced Mean A1C and Weight over 82 Weeks in Metformin-Treated Patients with Type 2 Diabetes (Abstract). Presented at the 87th Annual Meeting of The Endocrine Society’s, San Diego, CA, June 4-7, 2005. Poster 3-406.
Kendall D, Riddle M, Rosenstock J, Zhuang D, Kim D, Fineman M, Baron A. 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;28:1083-1091.
Kim D, MacConell L, Nielsen L, Zhuang D, Taylor K, Maggs D. Exenatide (Exendin-4) Reduced Mean A1C and Weight over 82 Weeks in Metformin- and Sulfonylurea-Treated Patients with Type 2 Diabetes (Abstract). Presented at the 87th Annual Meeting of The Endocrine Society’s, San Diego, CA, June 4-7, 2005. Oral session 8-5.
Blonde L, Han J, Mac S, et al. Exenatide (exendin-4) reduced A1C and weight over 82 weeks in overweight patients with type 2 diabetes. Presented at the 65th Scientific Sessions of the American Diabetes Association; San Diego, CA, June 10-14, 2005. Poster 477.
Poon T, Taylor K, Zhuang D, Shen L, Kim D, Fineman M. Exenatide Monotherapy Provides Glycemic Control Equivalent to That of Exenatide Combination Therapy in Subjects with Type 2 Diabetes (Abstract). Presented at the 87th Annual Meeting of The Endocrine Society’s, San Diego, CA, June 4-7, 2005. Poster 3-404.
Feinglos MN, Saad MF, Pi-Sunyer FX, An B, Santiago O. Effects of liraglutide (NN 2211), a long acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with type 2 diabetes. Diabetic Medicine 2005;22:1016-1023.
Ahrén B, Pacini G, Foley JE and Schweizer A. Improved meal related b-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care 2005;28:1936-1940.