Vnitr Lek 2008, 54(4):377-386
Exenatid and its position as antidiabetic drug in the treatment of type 2 diabetes mellitus
- Diabetologické centrum Interní kliniky 2. lékařské fakulty UK a FN Motol Praha, přednosta prof. MUDr. Milan Kvapil, CSc.
'Incretin effect' refers to increased insulin response to oral glucose as compared to i.v. glucose response. Incretin mimetics are a new class of antidiabetic drugs lowering hyperglycaemia. Incretin mimetics mimic the natural human hormones called 'incretins' with blood glucose regulating action. Exenatide is a synthetic analogue GLP-1 which is resistant to enzymatic degradation by DPP IV. Subcutaneously administered exenatide stimulates insulin secretion, suppresses glucagon secretion, slows down stomach evacuation and reduces the weight. Its administration is safe and the most frequent side effect is mild nausea.
Keywords: glucagon-like peptide 1; exenatid; type 2 diabetes mellitus
Received: March 9, 2008; Accepted: April 3, 2008; Published: April 1, 2008 Show citation
References
- Agerso H, Jensen LB, Elbrond B et al. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN a new long-acting GLP-1 derivative, in healthy men. Diabetologia 2002; 45: 195-202.
Go to original source...
Go to PubMed...
- Blonde L, Klein EJ, Han J et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006; 8:436-447.
Go to original source...
Go to PubMed...
- Bloomgarden TZ. Gut and adipocyte peptides. Diabetes Care 2006; 29(2): 450-456.
Go to original source...
Go to PubMed...
- Bray GM. Exenatide. Am J Health Syst Pharm 2006; 63: 411-418.
Go to original source...
Go to PubMed...
- Brunzell JD, Robertson RP, Lerner RL et al. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab 1976; 42(2): 222-229.
Go to original source...
Go to PubMed...
- Burceli R, Cani D, Knauf C. GLP-1 and cerebral detection of glucose a key mechanism for the regulation of glucose homeostasis. Med Sci 2006; 22(3): 237-239.
Go to original source...
- Buse JB, Henry RR, Han J et al, for the Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulphonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628-2635.
Go to original source...
Go to PubMed...
- Buteau J, El-Assaad W et al. Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia 2004; 47: 806-815.
Go to original source...
Go to PubMed...
- ByettaŇ. P&T QUIKŇ Reports. July 2005. Available at: http://www.thomsonhc.com. Accessed March 14, 2006.
- Calara F, Taylor K, Han J et al. A randomised, open-label, crossover study examining the effect of injection site on bioavailability of exenatide (synthetic exendin-4). Clin Ther 2005; 27: 210-215.
Go to original source...
Go to PubMed...
- D'Alessio DA, Sandova DA, Seeley RJ. New ways in which GLP-1 can regulate glucose homeostasis. J Clin Invest 2005, 115(12):s3406-3408
Go to original source...
Go to PubMed...
- Damci T et al. Orlistat augments postprandial increases in glucagons-like peptide 1 in obese type 2 patients. Diabetes Care 2004; 27: 1077-1080.
Go to original source...
Go to PubMed...
- 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: 1092-1100.
Go to original source...
Go to PubMed...
- Degn KB, Brock B, Juhl CB et al. Effect of intravenous infusion of exenatide (synthetic exendin 4) on glucose-dependent insulin secretion and counter-regulation during hypoglycemia. Diabetes 2004; 53: 2397-2403.
Go to original source...
Go to PubMed...
- Del Prato S, Tiengo A. The importance of first phase secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab Res Rev 2001; 17: 164-174.
Go to original source...
Go to PubMed...
- Doggrell SA. Recent evidence of sustained benefit with exenatide in type 2 evidence. Expert Opin Pharmacother 2006, 7(14): 2003-2006.
Go to original source...
Go to PubMed...
- Drucker DJ. Development of glucagon-like peptide-1-based pharmaceuticals as therapeutic agents for the treatment of diabetes. Curr Pharm Des 2001; 7: 1399-1412.
Go to original source...
Go to PubMed...
- Drucker DJ. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 2002; 122: 531-544.
Go to original source...
Go to PubMed...
- Dupré J, Behme TM, McDonald TJ. Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab 2004; 89(7): 3469-3473.
Go to original source...
Go to PubMed...
- Exenatide injection /package insert/. San Diego, Calif: Amylin Pharmaceuticals, Inc; April 2005.
- Fehse F, Trautman M, Holst JJ et al. Exenatide augments first and second phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes, J Clin Endocrinol Metab 2005; 90: 5991-5997.
Go to original source...
Go to PubMed...
- Fineman MS, Bicsak TA, Shen LZ et al. Effect of glycemic control of exenatide (synthetic exendin 4) additive to existing metformin and/or sulphonylurea treatment in patients with type 2 diabetes. Diabetes Care 2003; 26: 2370-2377.
Go to original source...
Go to PubMed...
- Franklin I, Gromada J et al. Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagons release. Diabetes 2005; 54: 1808-1815.
Go to original source...
Go to PubMed...
- Gautier JF, Fetita S et al. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab 2005; 31:233-242.
Go to original source...
Go to PubMed...
- Gedulin BR, Nikoulina SE, Smith PA et al. Exenatide (exendin 4) improves insulin sensitivity and b-cell mass in insulin resistant obese fa/fa Ucker rats independent of glycemia and body weight. Endocrinology 2005; 146: 2069-2076.
Go to original source...
Go to PubMed...
- Gonzalez N, Acitore A et al. Effect of GLP-1 on glucose transport and its cell signalling in human myocytes. Regul Pept 2005; 126: 203-211.
Go to original source...
Go to PubMed...
- Heine RJ, VanGall 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: 559-569
Go to original source...
Go to PubMed...
- Henkel H et al. Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus. Metab Clin Exp 2005; 54: 1168-73.
Go to original source...
Go to PubMed...
- Hood R, Valentine V et al. Use of exenatide in patients with type 2 diabetes. Diabetes Spect 2006; 19(3): 181-186.
Go to original source...
- Hui H, Farilla L, Merkel P. The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects. Eur J Endocrinol 2002, 146(6): 863-869.
Go to original source...
Go to PubMed...
- Iltz JL, Baker DE et al. Exenatide: An incretin mimetic for the treastment of type 2 diabetes mellitus. Clin Ther 2006; 28(5): 652-664.
Go to original source...
Go to PubMed...
- Keating GM. Exenatide. Drugs 2005; 65(12): 1681-1692.
Go to original source...
Go to PubMed...
- 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 metformim and sulphonylurea. Diabetes Care 2005; 28: 1083-1091.
Go to original source...
Go to PubMed...
- Kolterman OG, Buse JB, Fineman MS 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: 3082-89.
Go to original source...
Go to PubMed...
- Kothare PA, Soon DK et al. Effect of exenatide on the steadystate pharmacokinetics of digoxin. J Clin Pharmacol 2005; 45: 1032-1037.
Go to original source...
Go to PubMed...
- Li L, El-Kholy W et al. Glucagon-like peptide-1 protects beta cells from cytokine-induced apaptosis and necrosis: role of protein kinase B. Diabetologia 2005; 48: 1339-1349.
Go to original source...
Go to PubMed...
- McGarry JD. Banting Lecture 2001: Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51: 7-18.
Go to original source...
Go to PubMed...
- Meier JJ, Gethmann A, Goetze O et al. Glucagon-like peptide 1 (GLP-1) abolishes the postprandial rise in triglyceride concentrations and lowers free fatty acid levels in humans. Diabetologia 2006; 49: 452-458.
Go to original source...
Go to PubMed...
- Meier JJ, Naunck MA, Krantz D et al. Secretion, degradation and elimination of glucagons-like peptide (GLP-1) and gastric inhibitory polypeptide (GIP) in patients with chronic renal insufficiency and healthy controls. Diabetes 2004; 53: 654-662.
Go to original source...
Go to PubMed...
- Meier JJ, Gethmann A, Nauck MA et al. The glucagon-like peptide-1 metabolite GLP-1-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans. Am J Physiol Endocrinol Metab 2006; 290(6): E1118-11123.
Go to original source...
Go to PubMed...
- Meneilly GS et al. Effects of 3 months of continuous subcutaneous administration of glucagons-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care 2003; 26(10): 2835-2841.
Go to original source...
Go to PubMed...
- Nielsen LL, Young AA, Parkes DG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 2004; 117: 77-88.
Go to original source...
Go to PubMed...
- Nikolaidis LA, Elahi D, Shen YT, Shanon RP. Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 2005; 289: H2401-H2408.
Go to original source...
Go to PubMed...
- Peyot M-L, Nolan JC et al. Hormone-Sensitive lipase has a role in lipid signalling for insulin secretion but is nonessential for the incretin action of glucagons-like peptide-1. Diabetes 2004; 53: 1733-1742.
Go to original source...
Go to PubMed...
- Pratley RE, Weyer C. The role of impared early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 2001; 44: 929-945.
Go to original source...
Go to PubMed...
- Ratner RE, Maggs D, Nielsen LL et al. Long-term effects of exenatide therapy over 82 weeks on glycemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab 2006; 8(4): 419-428.
Go to original source...
Go to PubMed...
- Riddle CM, Henry RR, Poon TH et al. Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin. Diabetes Metab Res Rev 2006; 22(6): 483-491.
Go to original source...
Go to PubMed...
- Secnik BK, Matza LS, Oglesby A et al. Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes. Health Qual Life Outcomes 2006, 11(4): 80-85.
Go to original source...
Go to PubMed...
- Sörhede Winzel M, Ahrén B. Glucagon-like peptide-1 and islet lipolysis. Horm Metab Res 2004; 36: 795-803.
Go to original source...
Go to PubMed...
- Taylor K, Kim D, Nielsen LL et al. Daylong subcutaneous infusion of exenatide lowers glycemia in patients with type 2 diabetes. Horm Metab Res 2005; 37: 627-632.
Go to original source...
Go to PubMed...
- Vella A, Shah P, Reed AS et al. Lack of effect of exendin-4 and glucagon-like peptide 1-(7,36)-amide on insulin action in non-diabetic humans. Diabetologia 2002; 45: 1410-1415.
Go to original source...
- Vella A, Shaw P, Basu R et al. Effect of glucagon-like peptide 1-(7,36)-amide on initial splanchnic glucose uptake and insulin action in humans with type 1 diabetes. Diabetes 2001; 50: 565-572.
Go to original source...
Go to PubMed...
- Visboll T, Krarup T et al. Reduced postprandial concentrations of intact biologically active glucagons-like peptide 1 in type 2 diabetic patients. Diabetes 2001; 50: 609-613.
Go to original source...
Go to PubMed...
- Visboll 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: 1111-1119.
Go to original source...
Go to PubMed...
- Vilsboll T, Holst JJ. Incretins, insulin secretion and type 2 diabetes mellitus. Diabetologia 2004; 47: 357-366
Go to original source...
Go to PubMed...
- Vilsboll T, Krarup T, Sonne J et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88: 2706-2713
Go to original source...
Go to PubMed...
- Wettergren A, Schjoldager B, Mortensen PE et al. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993; 38: 665-673.
Go to original source...
Go to PubMed...
- Yaney GC et al. Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic beta-cells (HIT). Diabetes 2001; 50: 56-62.
Go to original source...
Go to PubMed...
- Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity and beta-cell function in type 2 diabetes a parallel-group study. Lancet 2002; 359: 824-830.
Go to original source...
Go to PubMed...