1,876
Views
43
CrossRef citations to date
0
Altmetric
Reviews

GLP-1 agonists for type 2 diabetes: pharmacokinetic and toxicological considerations

, & , MD
Pages 17-29 | Published online: 24 Oct 2012

Bibliography

  • Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87(4):1409-39
  • Vilsboll T, Christensen M, Junker AE, Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012;344:d7771
  • Shyangdan DS, Royle PL, Clar C, Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis. BMC Endocr Disord 2010;10:20
  • Christensen M, Knop FK. Once-weekly GLP-1 agonists: how do they differ from exenatide and liraglutide? Curr Diab Rep 2010;10(2):124-32
  • Vollmer K, Holst JJ, Baller B, Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 2008;57(3):678-87
  • Hare KJ, Knop FK. Incretin-based therapy and type 2 diabetes. Vitam Horm 2010;84:389-413
  • Mortensen K, Christensen LL, Holst JJ, Orskov C. GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept 2003;114(2-3):189-96
  • Reimann F, Gribble FM. Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes 2002;51(9):2757-63
  • Gribble FM, Williams L, Simpson AK, Reimann F. A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line. Diabetes 2003;52(5):1147-54
  • Tolhurst G, Reimann F, Gribble FM. Intestinal sensing of nutrients. Handb Exp Pharmacol 2012;209:309-35
  • Thomas C, Gioiello A, Noriega L, TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009;10(3):167-77
  • Carr RD, Larsen MO, Winzell MS, Incretin and islet hormonal responses to fat and protein ingestion in healthy men. Am J Physiol Endocrinol Metab 2008;295(4):E779-84
  • Thondam SK, Cross A, Cuthbertson DJ, Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with Type 2 diabetes mellitus. Diabet Med 2012;29(8):e205-10
  • Imeryuz N, Yegen BC, Bozkurt A, Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol 1997;273(4 Pt 1):G920-7
  • Herrmann-Rinke C, Voge A, Hess M, Goke B. Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 1995;147(1):25-31
  • Dube PE, Brubaker PL. Nutrient, neural and endocrine control of glucagon-like peptide secretion. Horm Metab Res 2004;36(11-12):755-60
  • Kjems LL, Holst JJ, Volund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003;52(2):380-6
  • Vilsboll T, Krarup T, Deacon CF, Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001;50(3):609-13
  • Toft-Nielsen MB, Damholt MB, Madsbad S, Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86(8):3717-23
  • Nauck MA, Vardarli I, Deacon CF, Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down? Diabetologia 2011;54(1):10-18
  • Calanna S, Gluud LL, Holst JJ, Glucagon-Like Peptide-1 in Patients with Type 2 Diabetes Mellitus - Systematic Review and Meta-analysis of Clinical Studies. ADA; 2012
  • Mentlein R, Dipeptidyl-peptidase IV. CD26)–role in the inactivation of regulatory peptides. Regul Pept 1999;85(1):9-24
  • 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(9):1126-31
  • 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(8):3585-96
  • Hupe-Sodmann K, Goke R, Goke B, Endoproteolysis of glucagon-like peptide (GLP)-1 (7-36) amide by ectopeptidases in RINm5F cells. Peptides 1997;18(5):625-32
  • Plamboeck A, Holst JJ, Carr RD, Deacon CF. Neutral endopeptidase 24.11 and dipeptidyl peptidase IV are both mediators of the degradation of glucagon-like peptide 1 in the anaesthetised pig. Diabetologia 2005;48(9):1882-90
  • Hansen L, Deacon CF, Orskov C, Holst JJ. Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology 1999;140(11):5356-63
  • Deacon CF, Pridal L, Klarskov L, Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am J Physiol 1996;271(3 Pt 1):E458-64
  • Carone FA, Peterson DR, Flouret G. Renal tubular processing of small peptide hormones. J Lab Clin Med 1982;100(1):1-14
  • Deacon CF. What do we know about the secretion and degradation of incretin hormones? Regul Pept 2005;128(2):117-24
  • Rachman J, Gribble FM, Barrow BA, Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7-36) amide in patients with NIDDM. Diabetes 1996;45(11):1524-30
  • 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(9309):824-30
  • Vilsboll T, Toft-Nielsen MB, Krarup T, Evaluation of beta-cell secretory capacity using glucagon-like peptide 1. Diabetes Care 2000;23(6):807-12
  • Ritzel R, Orskov C, Holst JJ, Nauck MA. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships. Diabetologia 1995;38(6):720-5
  • Orskov C, Poulsen SS, Moller M, Holst JJ. Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I. Diabetes 1996;45(6):832-5
  • Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia 2006;49(2):253-60
  • Thorens B, Porret A, Buhler 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(11):1678-82
  • Assessment report for Byetta. European Medicines Agency; 2010
  • Edwards CM, Stanley SA, Davis R, Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001;281(1):E155-61
  • Kolterman OG, Kim DD, Shen L, Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm 2005;62(2):173-81
  • Copley K, McCowen K, Hiles R, Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab 2006;7(4):367-74
  • Linnebjerg H, Kothare PA, Park S, Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol 2007;64(3):317-27
  • Blase E, Taylor K, Gao HY, 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(5):570-7
  • Kothare PA, Linnebjerg H, Skrivanek Z, Exenatide effects on statin pharmacokinetics and lipid response. Int J Clin Pharmacol Ther 2007;45(2):114-20
  • Linnebjerg H, Kothare P, Park S, The effect of exenatide on lisinopril pharmacodynamics and pharmacokinetics in patients with hypertension. Int J Clin Pharmacol Ther 2009;47(11):651-8
  • Kothare PA, Soon DK, Linnebjerg H, Effect of exenatide on the steady-state pharmacokinetics of digoxin. J Clin Pharmacol 2005;45(9):1032-7
  • Soon D, Kothare PA, Linnebjerg H, Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy Asian men. J Clin Pharmacol 2006;46(10):1179-87
  • Norris SL, Lee N, Thakurta S, Chan BK. Exenatide efficacy and safety: a systematic review. Diabet Med 2009;26(9):837-46
  • Aroda VR, Ratner R. The safety and tolerability of GLP-1 receptor agonists in the treatment of type 2 diabetes: a review. Diabetes Metab Res Rev 2011;27(6):528-42
  • Fineman MS, Shen LZ, Taylor K, 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 2004;20(5):411-17
  • 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-controlled and comparator-controlled clinical trials. Diabetes Metab Syndr Obes 2012;5:29-41
  • Elashoff M, Matveyenko AV, Gier B, Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141(1):150-6
  • Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care 2009;32(5):834-8
  • Spranger J, Gundert-Remy U, Stammschulte T. GLP-1-based therapies: the dilemma of uncertainty. Gastroenterology 2011;141(1):20-3
  • 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(11):2349-54
  • Gier B, Matveyenko AV, Kirakossian D, Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the KrasG12D mouse model. Diabetes 2012;61(5):1250-62
  • Gale EA. GLP-1-based therapies and the exocrine pancreas: more light, or just more heat? Diabetes 2012;61(5):986-8
  • Buse JB, Garber A, Rosenstock J, Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab 2011;96(6):1695-702
  • Mendis B, Simpson E, Macdonald I, Mansell P. Investigation of the haemodynamic effects of exenatide in healthy male subjects. Br J Clin Pharmacol 2012;74(3):437-44
  • Nauman J, Janszky I, Vatten LJ, Wisloff U. Temporal changes in resting heart rate and deaths from ischemic heart disease. JAMA 2011;306(23):2579-87
  • Ratner R, Han J, Nicewarner D, Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol 2011;10:22
  • Assessment report for Bydureon. 2012
  • Fineman M, Flanagan S, Taylor K, Pharmacokinetics and pharmacodynamics of exenatide extended-release after single and multiple dosing. Clin Pharmacokinet 2011;50(1):65-74
  • Drucker DJ, Buse JB, Taylor K, Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008;372(9645):1240-50
  • Bergenstal RM, Wysham C, Macconell L, 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):431-9
  • Diamant M, Van GL, Stranks S, Safety and efficacy of once-weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes over 84 weeks. Diabetes Care 2012;35(4):683-9
  • Assessment report for Victoza. European Medicines Agency; 2009
  • Elbrond B, Jakobsen G, Larsen S, Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care 2002;25(8):1398-404
  • Agerso H, Jensen LB, Elbrond B, The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 2002;45(2):195-202
  • Malm-Erjefalt M, Bjornsdottir I, Vanggaard J, Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos 2010;38(11):1944-53
  • Jacobsen LV, Hindsberger C, Robson R, Zdravkovic M. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br J Clin Pharmacol 2009;68(6):898-905
  • Jacobsen LV, Vouis J, Hindsberger C, Zdravkovic M. Treatment with liraglutide–a once-daily GLP-1 analog–does not reduce the bioavailability of ethinyl estradiol/levonorgestrel taken as an oral combination contraceptive drug. J Clin Pharmacol 2011;51(12):1696-703
  • Zdravkovic M, Ekblom M, Brøndsted L, The effect of liraglutide on the absorption pharmacokinetics of concomitant oral drugs with different solubility and permeability properties in healthy subjects. Diabetologia 2008;51(Suppl 1):S890
  • Jelsing J, Vrang N, Hansen G, Liraglutide: short-lived effect on gastric emptying-long lasting effects on body weight. Diabetes Obes Metab 2012;14(6):531-8
  • Morrow L, Hompesch M, Guthrie H, Co-administration of liraglutide with insulin detemir demonstrates additive pharmacodynamic effects with no pharmacokinetic interaction. Diabetes Obes Metab 2011;13(1):75-80
  • Garber A, Henry R, Ratner R, Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009;373(9662):473-81
  • Nauck M, Frid A, Hermansen K, Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009;32(1):84-90
  • Russell-Jones D, Vaag A, Schmitz O, Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia 2009;52(10):2046-55
  • 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(9683):39-47
  • Bjerre KL, Madsen LW, Andersen S, Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010;151(4):1473-86
  • Hegedus L, Moses AC, Zdravkovic M, GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab 2011;96(3):853-60
  • Endocrine and Metabolic Drug Advisory Committee. Liraglutide (injection) for the Treatment of Patients with Type 2 Diabetes NDA 22-34 Briefing Document. 2009
  • Nyborg NC, Molck AM, Madsen LW, Bjerre KL. The human GLP-1 analog liraglutide and the pancreas: evidence for the absence of structural pancreatic changes in three species. Diabetes 2012;61(5):1243-9
  • Marre M, Shaw J, Brandle M, Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med 2009;26(3):268-78
  • Zinman B, Gerich J, Buse JB, Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care 2009;32(7):1224-30
  • Marso SP, Lindsey JB, Stolker JM, Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies. Diab Vasc Dis Res 2011;8(3):237-40
  • Christensen M, Bagger JI, Vilsboll T, Knop FK. The alpha-cell as target for type 2 diabetes therapy. Rev Diabet Stud 2011;8(3):369-81
  • Gallwitz B, Anorexigenic effects of GLP-1 and Its analogues. Handb Exp Pharmacol 2012;209:185-207
  • Astrup A, Carraro R, Finer N, Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond) 2012;36(6):843-54
  • Kielgast U, Holst JJ, Madsbad S. Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual beta-cell function. Diabetes 2011;60(5):1599-607
  • Buse JB, Nauck MA, Forst T, Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomised, open-label study. EASD 47th Annual Meeting; 14 September 2011
  • GSK receives initial data from the first completed phase lll study of albiglutide in type 2 diabetes. 16-112011.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.