Pharmacokinetic drug evaluation of exenatide for the treatment of type 2 diabetes

References

• International Diabetes Federation. IDF diabetes atlas. 2015. 7th ed. Available from: http://www.diabetesatlas.org/
   Google Scholar
• Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017 Jun 3;389(10085):2239–2251. DOI:10.1016/S0140-6736(17)30058-2
   PubMed Web of Science ®Google Scholar
• Elrick H, Stimmler L, Hlad CJ, et al. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab. 1964;24:1076–1082.
   PubMed Web of Science ®Google Scholar
• Tasyurek HM, Altunbas HA, Balci MK, et al. Incretins: their physiology and application in the treatment of diabetes mellitus. Diabetes Metab Res Rev. 2014 Jul;30(5):354–371. DOI:10.1002/dmrr.2501
   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(3–4):179–188.
   PubMedGoogle Scholar
• Nauck M. Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2016 Mar;18(3):203–216. DOI:10.1111/dom.12591
   PubMed Web of Science ®Google Scholar
• American Diabetes Association. Standards of medical care in diabetes 2017. Diabetes Care. 2017 Jan;40(S1): S64-S74.
   Google Scholar
• Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2017. Endocr Pract. 2017 Feb;23(2).
   Web of Science ®Google Scholar
• Tomlinson B, Hu M, Zhang Y, et al. An overview of new GLP-1 receptor agonists for type 2 diabetes. Expert Opin Investig Drugs. 2016;25(2):145–158. DOI:10.1517/13543784.2016.1123249
   PubMed Web of Science ®Google Scholar
• Henry RR, Rosenstock J, Logan D, et al. Continuous subcutaneous delivery of exenatide via ITCA 650 leads to sustained glycemic control and weight loss for 48 weeks in metformin-treated subjects with type 2 diabetes. J Diabetes Complications. 2014 May-Jun;28(3):393–398. DOI:10.1016/j.jdiacomp.2013.12.009
   PubMed Web of Science ®Google Scholar
• Intarcia announces FDA filing acceptance of new drug application (NDA) for ITCA 650 for the treatment of type 2 diabetes. [cited 2017 Jul 04]. Available from: https://www.intarcia.com/media/pressreleases/2017-feb-3-intarcia-announces-fda-filing-acceptance.html
   Google Scholar
• Ueno H, Mizuta M, Shiiya T, et al. Exploratory trial of intranasal administration of glucagon-like peptide-1 in Japanese patients with type 2 diabetes. Diabetes Care. 2014 Jul;37(7):2024–2027. DOI:10.2337/dc13-0690
   PubMed Web of Science ®Google Scholar
• Bailey CJ, Tahrani AA, Barnett AH. Future glucose-lowering drugs for type 2 diabetes. Lancet Diabetes Endocrinol. 2016 Apr;4(4):350–359. DOI:10.1016/S2213-8587(15)00462-3
   PubMed Web of Science ®Google Scholar
• Meier JJ, Nauck MA. Incretin-based therapies: where will we be 50 years from now? Diabetologia. 2015 Aug;58(8):1745–1750. DOI:10.1007/s00125-015-3608-6
   Google Scholar
• Eng J, Kleinman WA, Singh L, et al. 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;267:7402–7405.
   PubMed Web of Science ®Google Scholar
• Bhavsar S, Mudaliar S, Cherrington A. Evolution of exenatide as diabetes therapeutic. Curr Diabetes Rev. 2013 Mar 1;9(2):161–193.
   PubMedGoogle Scholar
• Hui H, Zhao X, Perfetti R. Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing of a novel pharmacological agent for the treatment of diabetes. Diabetes Metab Res Rev. 2005 Jul-Aug;21(4):313–331.
   PubMed Web of Science ®Google Scholar
• 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;13(11):1145–1154.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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;88:3082–3089.
   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;87:1282–1290.
   PubMed Web of Science ®Google Scholar
• Degn KB, Brock B, Juhl CB, et al. Effect of intravenous infusion exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes. 2004;53:2397–2403.
   PubMed Web of Science ®Google Scholar
• McCormack PL. Exenatide twice daily: a review of its use in the management of patients with type 2 diabetes mellitus. Drugs. 2014 Mar;74(3):325–351. DOI:10.1007/s40265-013-0172-6
   PubMed Web of Science ®Google Scholar
• Copley K, McCowen K, Hiles R, et al. Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab. 2006;7:367–374.
   PubMed Web of Science ®Google Scholar
• Blase E, Taylor K, Gao HY, et al. 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. 2005;45:570–577.
   PubMed Web of Science ®Google Scholar
• Linnebjerg H, Park S, Kothare P, et al. Exenatide delays gastric emptying and reduces postprandial glucose in type 2 diabetes [abstract no. 0223]. Diabetologia. 2006;49(Suppl. 1):140.
   Google Scholar
• 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;24:2943–2952.
   PubMed Web of Science ®Google Scholar
• Pinelli NR, Jantz A, Smith Z, et al. Effect of administration time of exenatide on satiety responses, blood glucose, and adverse events in healthy volunteers. J Clin Pharmacol. 2011;51:165–172.
   PubMed Web of Science ®Google Scholar
• 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. 2001;281:E155–61.
   PubMed Web of Science ®Google Scholar
• Drucker DJ. Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol. 2003;17:161–171.
   PubMed Web of Science ®Google Scholar
• 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;24:275–286.
   PubMed Web of Science ®Google Scholar
• Cvetkovic RS, Plosker GL. Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs. 2007;67(6):935–954.
   PubMed Web of Science ®Google Scholar
• Fehse FC, Trautmann ME, 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.
   PubMed Web of Science ®Google Scholar
• Malloy J, Capparelli E, Gottschalk M, et al. Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study. Clin Ther. 2009;31(4):806–815.
   PubMed Web of Science ®Google Scholar
• Kothare PA, Linnebjerg H, Isaka Y, et al. Pharmacokinetics, pharmacodynamics, tolerability, and safety of exenatide in Japanese patients with type 2 diabetes mellitus. J Clin Pharmacol. 2008;48(12):1389–1399.
   PubMed Web of Science ®Google Scholar
• 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. 2005;27(2):210–215.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Byetta (exenatide): summary of product characteristics. 2016. [cited 2017 Jul]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000698/WC500051845.pdf
   Google Scholar
• US FDA. Byetta (exenatide) injection: US prescribing information. 2009. [cited 2017 Jul]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021773s9s11s18s22s25lbl.pdf
   Google Scholar
• Linnebjerg H, Kothare PA, Seger M, et al. Exenatide: pharmacokinetics, pharmacodynamics, safety and tolerability in patients >75 years of age with type 2 diabetes. Int J Clin Pharmacol Ther. 2011;49(2):99–108.
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacokinetics and clinical use of incretin-based therapies in patients with chronic kidney disease and type 2 diabetes. Clin Pharmacokinet. 2015;51:1–21.
   Web of Science ®Google Scholar
• Fineman M, Flanagan S, Taylor K, et al. Pharmacokinetics and pharmacodynamics of exenatide extended-release after single and multiple dosing. Clin Pharmacokinet. 2011;50:65–74.
   PubMed Web of Science ®Google Scholar
• Linnebjerg H, Kothare PA, Park S, et al. Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol. 2007;64(3):317–327.
   PubMed Web of Science ®Google Scholar
• 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(5):1092–1100.
   PubMed Web of Science ®Google Scholar
• 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;27:2628–2635.
   PubMed Web of Science ®Google Scholar
• 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 mellitus treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083–1091.
   PubMed Web of Science ®Google Scholar
• Blonde L, Klein EJ, Han J, et al. Interin 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.
   PubMed Web of Science ®Google Scholar
• Derosa G, Maffioli P, Salvadeo SAT, et al. Exenatide versus glibenclamide in patients with diabetes. Diabetes Technol Ther. 2010;12(3):233–240.
   PubMed Web of Science ®Google Scholar
• Derosa G, Putignano P, Bossi AC, et al. Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients. Eur J Pharmacol. 2011;666(1–3):251–256.
   PubMed Web of Science ®Google Scholar
• Gallwitz B, Guzman J, Dotta F, et al. Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial. Lancet. 2012;379(9833):2270–2278.
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Triplitt C, Qu Y, et al. Effects of exenatide plus rosiglitazone on b-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin. Diabetes Care. 2010;33(5):951–957.
   PubMed Web of Science ®Google Scholar
• Deacon CF, Mannucci E, Ahrén B. Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on-theraphy to metformin in subjects with type 2 diabetes-a review and meta analysis. Diabetes Obes Metab. 2012;14:762–767.
   PubMed Web of Science ®Google Scholar
• 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, openlabel trial (LEAD-6). Lancet. 2009;374(9683):39–47.
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Raccah D, Koranyi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care. 2013;36(10):2945–2951.
   PubMed Web of Science ®Google Scholar
• 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(11):2333–2348.
   PubMed Web of Science ®Google Scholar
• Davies MJ, Donnelly R, Barnett AH, et al. Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the helping evaluate exenatide in patients with diabetes compared with long-acting insulin (HEELA) study. Diabetes Obes Metab. 2009;11(12):1153–1162.
   PubMed Web of Science ®Google Scholar
• 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(8):559–569.
   PubMed Web of Science ®Google Scholar
• Bergenstal R, Lewin A, Bailey T, et al. Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea. Curr Med Res Opin. 2009;25(1):65–75.
   PubMed Web of Science ®Google Scholar
• Gallwitz B, Böhmer M, Segiet T, et al. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011;34(3):604–606.
   PubMed Web of Science ®Google Scholar
• 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(2):259–267.
   PubMed Web of Science ®Google Scholar
• Diamant M, Nauck MA, Shaginian R, et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763–2773. DOI:10.2337/dc14-0876
   PubMed Web of Science ®Google Scholar
• Raskin P, Mohan A. Comparison of once-weekly with twice-daily exenatide in the treatment of type 2 diabetes (DURATION-1 trial). Expert Opin Pharmacother. 2010;11(13):2269–2271.
   PubMed Web of Science ®Google Scholar
• Bergenstal RM, Wysham C, Macconell L, et al. DURATION-2 Study Group. 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(9739):431–439.
   PubMed Web of Science ®Google Scholar
• Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an openlabel randomised trial. Lancet. 2010;375(9733):2234–2243.
   PubMed Web of Science ®Google Scholar
• Russell-Jones D, Cuddihy RM, Hanefeld M, et al. DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012;35(2):252–258.
   PubMed Web of Science ®Google Scholar
• 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(5):1301–1310.
   PubMed Web of Science ®Google Scholar
• Buse JB, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381(9861):117–124.
   PubMed Web of Science ®Google Scholar
• Frías JP, Rosenstock J, Somogyi A, et al. Efficacy and safety of exenatide QW vs. Placebo added to insulin glargine in uncontrolled basal-insulin treated type 2 diabetes: DURATION-7 trial [abstract no. 132 OR] In: American Diabetes Association 77th scientific sessions. 2017.
   Google Scholar
• Frías JP, Guja C2, Hardy E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016 Dec 4;(12):1004–1016. DOI:10.1016/S2213-8587(16)30267-4
   PubMed Web of Science ®Google Scholar
• Wysham C, Rosenstock J, Malloy J, et al. DURATION-NEO-1: greater HbA1c reductions with exenatide suspension once weekly by autoinjector pen vs exenatide twice daily in inadequately controlled type 2 diabetes. Diabetologia. 2014;57:S109.
   Web of Science ®Google Scholar
• 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(6):1255 1261.
   Web of Science ®Google Scholar
• Wysham CH, MacConell LA2, Maggs DG, et al. Five-year efficacy and safety data of exenatide once weekly: long-term results from the DURATION-1 randomized clinical trial. Mayo Clin Proc. 2015 Mar;90(3):356–365. DOI:10.1016/j.mayocp.2015.01.008
   PubMed Web of Science ®Google Scholar
• Henry RR, Klein EJ, Han J, et al. Efficacy and tolerability of exenatide once weekly over 6 years in patients with type 2 diabetes: an uncontrolled open-label extension of the DURATION-1 study. Diabetes Technol Ther. 2016 Nov;18(11):677–686.
   PubMed Web of Science ®Google Scholar
• Wysham CH, Philis-Tsimikas A, Klein EJ, et al. DURATION-1 extension in patients with T2D: efficacy and tolerability of exenatide once weekly (QW) over 7 years [abstract no. 1041 P] In: American Diabetes Association 76th scientific sessions. 2016.
   Google Scholar
• Gadde KM, Vetter ML, Iqbal N, et al. Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: the DURATION-NEO-2 randomized clinical study. Diabetes Obes Metab. 2017 Jul;19(7):979–988. DOI:10.1111/dom.12908
   PubMed Web of Science ®Google Scholar
• 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. Diabetic Med. 2011;28(6):705–714.
   PubMed Web of Science ®Google Scholar
• Diamant M, VanGaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3):3-year results of an open-label randomized trial. Lancet Diabetes Endocrinol. 2014;2:464–473.
   PubMed Web of Science ®Google Scholar
• Guja C, Frías JP, Azazuddin A, et al. DURATION-8 randomized controlled trial 1-year results: efficacy and safety of once-weekly exenatide (ExQW) plus once-daily dapagliflozin (DAPA) versus ExQW or DAPA alone [abstract no. 141 LB] In: American Diabetes Association 77th scientific sessions. 2017.
   Google Scholar
• Brunton S, Davidson JA. Exenatide once weekly: a review of pharmacology and treatment considerations in type 2 diabetes. Clin Ther. 2016 Mar;38(3):582–594. DOI:10.1016/j.clinthera.2016.01.014
   PubMed Web of Science ®Google Scholar
• Syed YY1, McCormack PL. Exenatide extended-release: an updated review of its use in type 2 diabetes mellitus. Drugs. 2015 Jul;75(10):1141–1152. DOI:10.1007/s40265-015-0420-z
   PubMed Web of Science ®Google Scholar
• MacConell L, Brown C, Gurney K, et al. Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo controlled and comparator-controlled clinical trials. Diabetes Metab Syndr Obes. 2012;5:29–41.
   PubMedGoogle Scholar
• MacConell L, Gurney K, Malloy J, et al. Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4,328 patients. Diabetes Metab Syndr Obes. 2015 May 18;8: 241–253. DOI:10.2147/DMSO.S77290
   PubMed Web of Science ®Google Scholar
• Bettge K, Kahle M, Abd El Aziz MS, et al. Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trialsstudying glucagon-like peptide-1 receptor agonists: a systematic analysis of published clinicaltrials. Diabetes Obes Metab. 2017;19(3):336–347.
   PubMed Web of Science ®Google Scholar
• Fineman MS, Mace KF, Diamant M, et al. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012;14(6):546–554.
   PubMed Web of Science ®Google Scholar
• Best JH, Hoogwerf BJ, Herman WH, et al. Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011;34(1):90–95.
   PubMed Web of Science ®Google Scholar
• Paul SK, Marso SP, Maggs D, et al. Long-term cardiovascular outcomes with exenatide twice daily compared to insulin: a retrospective observational study [abstract no. 1420-P]. Diabetes.. 2013;62(Suppl 1):A371.
   Google Scholar
• Ratner R, Han J, Nicewarner D, et al. Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol. 2011;10:22.
   PubMed Web of Science ®Google Scholar
• Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017 Sep 28;377(13):1228–1239. DOI:10.1056/NEJMoa1612917
   PubMed Web of Science ®Google Scholar
• May M, Schindler C. Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016;7(2):69–83.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Bydureon (exenatide): summary of product characteristics. 2017. [cited 2017 Jul]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/human/002020/WC500108241.pdf
   Google Scholar
• US FDA. Byetta (exenatide) injection: US prescribing information. 2012. [cited 2017 Jul]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022200s000lbl.pdf
   Google Scholar
• Blase E, Taylor K, Gao HY, et al. 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. 2005 May;45(5):570–577. DOI:10.1177/0091270004274432
   PubMed Web of Science ®Google Scholar
• Kothare PA, Soon DK, Linnebjerg H, et al. Effect of exenatide on the steady-state pharmacokinetics of digoxin. J Clin Pharmacol. 2005;45(9):1032–1037.
   PubMed Web of Science ®Google Scholar
• 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. 2006;46(10):1179–1187.
   PubMed Web of Science ®Google Scholar
• Kothare PA, Linnebjerg H, Skrivanek Z, et al. Exenatide effects on statin pharmacokinetics and lipid response. Int J Clin Pharmacol Ther. 2007;45:114–120.
   PubMed Web of Science ®Google Scholar
• Linnebjerg H, Kothare P, Park S, et al. The effect of exenatide on lisinopril pharmacodynamics and pharmacokinetics in patients with hypertension. Int J Clin Pharmacol Ther. 2009;47:651–658.
   PubMed Web of Science ®Google Scholar
• Kothare PA, Seger ME, Northrup J, et al. Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial. BMC Clin Pharmacol. 2012;12:8.
   PubMedGoogle Scholar
• European Medicines Agency. Byetta (exenatide) [cited 2017 Jul]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000698/human_med_000682.jsp&mid=WC0b01ac058001d124.
   Google Scholar
• Procedural steps taken and scientific information after the authorization. [cited 2017 Jul] Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Procedural_steps_taken_and_scientific_information_after_authorisation/human/000698/WC500051844.pdf
   Google Scholar
• Byetta Approval History. [cited 2017 Jul]. Available from: https://www.drugs.com/history/byetta.html
   Google Scholar
• European Medicines Agency. Bydureon (exenatide): procedural steps taken and scientific information after the authorization. [cited 2017 Jul]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/002020/WC500143525.pdf
   Google Scholar
• Bydureon Approval History. [cited 2017 Jul]. Available from: https://www.drugs.com/history/bydureon.html
   Google Scholar