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Exenatide: incretin therapy for patients with Type 2 diabetes mellitus

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Pages 671-690 | Published online: 10 Jan 2014

References

  • Fujioka K. Pathophysiology of Type 2 diabetes and the role of incretin hormones and β-cell dysfunction. JAAPA (Suppl.), 3–8 (2007).
  • Global guideline for Type 2 diabetes: recommendations for standard, comprehensive, and minimal care. Diabet. Med.23(6), 579–593 (2006).
  • Nathan DM, Buse JB, Davidson MB et al. Management of hyperglycaemia 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. Diabetologia49(8), 1711–1721 (2006).
  • Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in Type 2 diabetes. N. Engl. J. Med.358(6), 580–591 (2008).
  • Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with Type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA281(21), 2005–2012 (1999).
  • Gagliardi L, Wittert G. Management of obesity in patients with Type 2 diabetes mellitus. Curr. Diabetes Rev.3(2), 95–101 (2007).
  • 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). Lancet352(9131), 837–853 (1998).
  • Ohkubo Y, Kishikawa H, Araki E et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res. Clin. Pract.28(2), 103–117 (1995).
  • Fox KM, Gerber Pharmd RA, Bolinder B, Chen J, Kumar S. Prevalence of inadequate glycemic control among patients with Type 2 diabetes in the United Kingdom general practice research database: a series of retrospective analyses of data from 1998 through 2002. Clin. Ther.28(3), 3188–395 (2006).
  • Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among U.S. adults diagnosed with Type 2 diabetes: a preliminary report. Diabetes Care27(1), 17–20 (2004).
  • Liebl A, Mata M, Eschwege E. Evaluation of risk factors for development of complications in Type II diabetes in Europe. Diabetologia45(7), S23–S28 (2002).
  • Bloomgarden ZT, Dodis R, Viscoli CM, Holmboe ES, Inzucchi SE. Lower baseline glycemia reduces apparent oral agent glucose-lowering efficacy: a meta-regression analysis. Diabetes Care29(9), 2137–2139 (2006).
  • Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl. J. Med.7, 355(23), 2427–2443 (2006).
  • Del PS, Bianchi C, Marchetti P. β-cell function and anti-diabetic pharmacotherapy. Diabetes Metab. Res. Rev.23(7), 518–527 (2007).
  • Black C, Donnelly P, McIntyre L, Royle PL, Shepherd JP, Thomas S. Meglitinide analogues for Type 2 diabetes mellitus. Cochrane Database Syst. Rev.2, CD004654 (2007).
  • Ahren B. DPP-4 inhibitors. Best Pract. Res. Clin. Endocrinol. Metab.21(4), 517–533 (2007).
  • Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology132(6), 2131–2157 (2007).
  • Moore B. On the treatment of diabetus mellitus by acid extract of duodenal mucous membrane. Biochem. J.1(1), 28–38 (1906).
  • Elrick H, Stimmler L, Hlad CJ Jr, Rai Y. Plasma insulin response to oral and intravenous glucose administration. J. Clin. Endocrinol. Metab.24, 1076–1082 (1964)
  • Ahren B. Gut peptides and Type 2 diabetes mellitus treatment. Curr. Diab. Rep.3(5), 365–372 (2003).
  • Green BD, Flatt PR. Incretin hormone mimetics and analogues in diabetes therapeutics. Best Pract. Res. Clin. Endocrinol. Metab.21(4), 497–516 (2007).
  • Nauck MA, Homberger E, Siegel EG et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J. Clin. Endocrinol. Metab.63(2), 492–498 (1986).
  • Drucker DJ. Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol. Endocrinol.17(2), 161–171 (2003).
  • Drucker DJ. Glucagon-like peptide-1 and the islet β-cell: augmentation of cell proliferation and inhibition of apoptosis. Endocrinology144(12), 5145–5148 (2003).
  • Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J. Clin. Endocrinol. Metab.80(3), 952–957 (1995).
  • Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. 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.267(11), 7402–7405 (1992).
  • Barnett A. Exenatide. Expert. Opin Pharmacother.8(15), 2593–2608 (2007).
  • Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with Type 2 diabetes. Diabetes Care27(11), 2628–2635 (2004).
  • DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with Type 2 diabetes. Diabetes Care28(5), 1092–1100 (2005).
  • Fineman MS, Bicsak TA, Shen LZ et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with Type 2 diabetes. Diabetes Care26(8), 2370–2377 (2003).
  • 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.88(7), 3082–3089 (2003).
  • Nelson P, Poon T, Guan X, Schnabel C, Wintle M, Fineman M. The incretin mimetic exenatide as a monotherapy in patients with Type 2 diabetes. Diabetes Technol. Ther.9(4), 317–326 (2007).
  • Poon T, Nelson P, Shen L et al. Exenatide improves glycemic control and reduces body weight in subjects with Type 2 diabetes: a dose-ranging study. Diabetes Technol. Ther.7(3), 467–477 (2005).
  • 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.29(11), 2333–2348 (2007).
  • Dupre J, Behme MT, McDonald TJ. Exendin-4 normalized postcibal glycemic excursions in Type 1 diabetes. J. Clin. Endocrinol. Metab.89(7), 3469–3473 (2004).
  • Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG. Exenatide versus insulin glargine in patients with suboptimally controlled Type 2 diabetes: a randomized trial. Ann. Intern. Med.143(8), 559–569 (2005).
  • Kolterman OG, Kim DD, Shen L et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with Type 2 diabetes mellitus. Am. J. Health Syst. Pharm.62(2), 173–181 (2005).
  • Linnebjerg H, Kothare PA, Skrivanek Z et al. Exenatide: effect of injection time on postprandial glucose in patients with Type 2 diabetes. Diabet. Med.23(3), 240–245 (2006).
  • Mari A, Nielsen LL, Nanayakkara N, DeFronzo RA, Ferrannini E, Halseth A. Mathematical modeling shows exenatide improved β-cell function in patients with Type 2 diabetes treated with metformin or metformin and a sulfonylurea. Horm. Metab. Res.38(12), 838–844 (2006).
  • 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. Diabetologia50(2), 259–267 (2007).
  • Degn KB, Brock B, Juhl CB et al. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes53(9), 2397–2403 (2004).
  • Fehse F, Trautmann 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.90(11), 5991–5997 (2005).
  • Egan JM, Meneilly GS, Elahi D. Effects of 1-mo bolus subcutaneous administration of exendin-4 in Type 2 diabetes. Am. J. Physiol. Endocrinol. Metab.284(6), E1072–E1079 (2003).
  • Taylor K, Kim D, Nielsen LL, Aisporna M, Baron AD, Fineman MS. Day-long subcutaneous infusion of exenatide lowers glycemia in patients with Type 2 diabetes. Horm. Metab. Res.37(10), 627–632 (2005).
  • Woerle HJ, Albrecht M, Linke R et al. Importance of changes in gastric emptying for postprandial plasma glucose fluxes in healthy humans. Am. J. Physiol. Endocrinol. Metab.294(1), E103–E109 (2008).
  • Woerle HJ, Szoke E, Meyer C et al. Mechanisms for abnormal postprandial glucose metabolism in Type 2 diabetes. Am. J. Physiol. Endocrinol. Metab.290(1), E67–E77 (2006).
  • Woerle HJ, Meyer C, Dostou JM et al. Pathways for glucose disposal after meal ingestion in humans. Am. J. Physiol. Endocrinol. Metab.284(4), E716–E725 (2003).
  • Horowitz M, O’Donovan D, Jones KL, Feinle C, Rayner CK, Samsom M. Gastric emptying in diabetes: clinical significance and treatment. Diab. Med.19(3), 177–194 (2002).
  • Horowitz M, Edelbroek MAL, Wishart JM, Straathof JW. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia36(9), 857–862 (2003).
  • Edwards CM, Stanley SA, Davis R et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am. J. Physiol. Endocrinol. Metab.281(1), E155–E161 (2001).
  • Clements JA, Heading RC, Nimmo WS, Prescott LF. Kinetics of acetaminophen absorption and gastric emptying in man. Clin. Pharmacol. Ther.24(4), 420–431 (1978).
  • Baggio L, Adatia F, Bock T, Brubaker PL, Drucker DJ. Sustained expression of exendin-4 does not perturb glucose homeostasis, β-cell mass, or food intake in metallothionein-preproexendin transgenic mice. J. Biol. Chem.275(44), 34471–34477 (2000).
  • Toft-Nielsen MB, Madsbad S, Holst JJ. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in Type 2 diabetic patients. Diabetes Care22(7), 1137–1143 (1999).
  • Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest.101(3), 515–520 (1998).
  • Gutzwiller JP, Goke B, Drewe J et al. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut44(1), 81–86 (1999).
  • Copley K, McCowen K, Hiles R, Nielsen LL, Young A, Parkes DG. Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr. Drug Metab.7(4), 367–374 (2006).
  • Simonsen L, Holst JJ, Deacon CF. Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular filtration in anaesthetised pigs. Diabetologia49(4), 706–712 (2006).
  • Calara F, Taylor K, Han J et al. A randomized, open-label, crossover study examining the effect of injection site on bioavailability of exenatide (synthetic exendin-4). Clin. Ther.27(2), 210–215 (2005).
  • Linnebjerg H, Kothare PA, Park S et al. Effect of renal impairment on the pharmacokinetics of exenatide. Br. J. Clin. Pharmacol.64(3), 317–327 (2007).
  • Ratner RE, Maggs D, Nielsen LL et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with Type 2 diabetes mellitus. Diabetes Obes. Metab.8(4), 419–428 (2006).
  • Riddle MC, 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.22(6), 483–491 (2006).
  • 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.8(4), 436–447 (2006).
  • Buse JB, Klonoff DC, Nielsen LL et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with Type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin. Ther.29(1), 139–153 (2007).
  • 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.24(1), 275–286 (2008).
  • Fineman MS, Shen LZ, Taylor K, Kim DD, Baron AD. Effectiveness of progressive dose-escalation of exenatide (exendin-4) in reducing dose-limiting side effects in subjects with Type 2 diabetes. Diabetes Metab. Res. Rev.20(5), 411–417 (2004)
  • 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 Care28(5), 1083–1091 (2005).
  • Zinman B, Hoogwerf BJ, Duran GS et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled Type 2 diabetes: a randomized trial. Ann. Intern. Med.146(7), 477–485 (2007).
  • Malozowski S. Exenatide in combination therapy: small study, big market, and many unanswered questions. Ann. Intern. Med.146(7), 527–528 (2007).
  • Home PD. Comment on: Nauck MA, Duran S, Kim D et al. (2007). 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. Diabetologia50, 259–267 (2007).
  • Brodows RG, Qu Y, Johns D, Kim D, Holcombe JH. Quantifying the effect of exenatide and insulin glargine on postprandial glucose excursions in patients with Type 2 diabetes. Curr. Med. Res. Opin.24(5), 1395–1397 (2008).
  • Brodows R, Milton D, Mao J, Wintle M, Trautmann M. Predictors of achieving glycaemic targets in patients with Type 2 diabetes treated with exenatide or insulin. Diabetologia50(Suppl.1), S352–S353 (2007).
  • Davis SN, Johns D, Maggs D, Xu H, Northrup JH, Brodows RG. Exploring the substitution of exenatide for insulin in patients with Type 2 diabetes treated with insulin in combination with oral antidiabetes agents. Diabetes Care30(11), 2767–2772 (2007).
  • Denker PS, Dimarco PE. Exenatide (exendin-4)-induced pancreatitis: a case report. Diabetes Care29(2), 471 (2006).
  • Kothare PA, Linnebjerg H, Skrivanek Z et al. Exenatide effects on statin pharmacokinetics and lipid response. Int. J. Clin. Pharmacol. Ther.45(2), 114–120 (2007).
  • Kothare PA, Soon DK, Linnebjerg H et al. Effect of exenatide on the steady-state pharmacokinetics of digoxin. J. Clin. Pharmacol.45(9), 1032–1037 (2005).
  • Blase E, Taylor K, Gao HY, Wintle M, Fineman M. Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injection of exenatide (exendin-4) in healthy subjects. J. Clin. Pharmacol.45(5), 570–577 (2005).
  • Soon D, Kothare PA, Linnebjerg H et al. Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy Asian men. J. Clin. Pharmacol.46(10), 1179–1187 (2006).
  • Gedulin BR, Nikoulina SE, Smith PA et al. Exenatide (exendin-4) improves insulin sensitivity and β-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology146(4), 2069–2076 (2005).
  • Stoffers DA, Desai BM, DeLeon DD, Simmons RA. Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat. Diabetes52(3), 734–740 (2003).
  • Tourrel C, Bailbe D, Meile MJ, Kergoat M, Portha B. 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. Diabetes50(7), 1562–1570 (2001).
  • Tourrel C, Bailbe D, Lacorne M, Meile MJ, Kergoat M, Portha B. 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. Diabetes51(5), 1443–1452 (2002).
  • 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. Diabetes48(12), 2270–2276 (1999).
  • Gallwitz B. Exenatide in Type 2 diabetes: treatment effects in clinical studies and animal study data. Int. J. Clin. Pract.60(12), 1654–1661 (2006).
  • Ghofaili KA, Fung M, Ao Z et al. Effect of exenatide on β-cell function after islet transplantation in type 1 diabetes. Transplantation83(1), 24–28 (2007).
  • 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 Care30(6), 1487–1493 (2007).
  • Viswanathan P, Chaudhuri A, Bhatia R, Al-Atrash F, Mohanty P, Dandona P. Exenatide therapy in obese patients with Type 2 diabetes mellitus treated with insulin. Endocr. Pract.13(5), 444–450 (2007).

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