Glucagon-like peptide-1 receptor agonists
Native glucagon-like peptide-1 (GLP-1) is not practical for therapeutic use due to a short half-life caused by ubiquitous, fast, and effective in vivo degradation by the enzyme dipeptidyl peptidase-4 (DPP-4).
KeywordsInsulin Glargine Insulin Lispro Insulin Degludec Diabetes Obes
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- 1.Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists. Lancet. 2006;368:1696-1705.Google Scholar
- 2.Gallwitz B. Glucagon-like peptide-1 analogues for type 2 diabetes mellitus: current and emerging agents. Drugs. 2011;71:1675-1688.Google Scholar
- 3.Madsbad S, Kielgast U, Asmar M, Deacon CF, Torekov SS, Holst JJ. An overview of once-weekly glucagon-like peptide-1 receptor agonists–available efficacy and safety data and perspectives for the future. Diabetes Obes Metab. 2011;13:394-407.Google Scholar
- 4.Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8:728-742.Google Scholar
- 5.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.Google Scholar
- 6.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;379:2270-2278.Google Scholar
- 7.Nauck MA, Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med. 2011;124:S3-S18.Google Scholar
- 8.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 Care. 2007;30:1487-1493.Google Scholar
- 9.Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372:1240-1250.Google Scholar
- 10.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;33:1255-1261.Google Scholar
- 11.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.Google Scholar
- 12.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;14:546-554.Google Scholar
- 13.Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 200245:195-202.Google Scholar
- 14.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, open-label trial (LEAD-6). Lancet. 2009;374:39-47.Google Scholar
- 15.Pratley RE, Nauck M, Bailey T, et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010;375:1447-1456Google Scholar
- 16.Ratner RE, Rosenstock J, Boka G; DRI6012 Study Investigators. Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial. Diabet Med. 2010;27:1024-1032.Google Scholar
- 17.Forst T, Pfützner A. Pharmacological profile, efficacy and safety of lixisenatide in type 2 diabetes mellitus. Expert Opin Pharmacother. 2013;14:2281-2296Google Scholar
- 18.Petersen AB, Knop FK, Christensen M. Lixisenatide for the treatment of type 2 diabetes. Drugs Today (Barc). 2013;49:537-553.Google Scholar
- 19.Rosenstock J, Raccah D, Korányi 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;36:2945-2951.Google Scholar
- 20.Kapitza C, Forst T, Coester HV, et al. Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. Diabetes Obes Metab. 2013;15:642-649.Google Scholar
- 21.Trujillo JM, Nuffer W. Albiglutide: a new GLP-1 receptor agonist for the treatment of type 2 diabetes. Ann Pharmacother. 2014;48:1494-1501.Google Scholar
- 22.Home PD, Shamanna P, Stewart M, et al. Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5. Diabetes Obes Metab. 2015;17:179-187.Google Scholar
- 23.Weissman PN, Carr MC, Ye J, et al. HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea. Diabetologia. 2014;57:2475-2484.Google Scholar
- 24.Reusch J, Stewart MW, Perkins CM, et al. Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonist albiglutide (HARMONY 1 trial): 52-week primary endpoint results from a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes mellitus not controlled on pioglitazone, with or without metformin. Diabetes Obes Metab. 2014;16:1257-1264.Google Scholar
- 25.Ahrén B, Johnson SL, Stewart M, et al. HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care. 2014;37:2141-2148.Google Scholar
- 26.Rosenstock J, Fonseca VA, Gross JL, et al. Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro. Diabetes Care. 2014;37:2317-2325.Google Scholar
- 27.Pratley RE, Nauck MA, Barnett AH, et al. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol. 2014;2:289-297.Google Scholar
- 28.Amblee A. Dulaglutide for the treatment of type 2 diabetes. Drugs Today (Barc). 2014;50:277-289.Google Scholar
- 29.Barrington P, Chien JY, Showalter HD, et al. A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes. Diabetes Obes Metab. 2011;13:426-433.Google Scholar
- 30.Giorgino F, Benroubi M, Sun JH, et al. Efficacy and safety of once weekly dulaglutide vs insulin glargine in combination with metformin and glimepiride in type 2 diabetes patients (AWARD- 2). Diabetologia 2014;57 (suppl 1):OP38.Google Scholar
- 31.O’Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, Phase 3, non-inferiority trial. Lancet. 2014;384(9951):1349-1357.Google Scholar
- 32.Thompson AM, Trujillo JM. Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes. Ann Pharmacother. 2015;49:351-359.Google Scholar
- 33.Gotfredsen CF, Mølck AM, Thorup I, et al. The human GLP-1 analogs liraglutide and semaglutide: absence of histopathological effects on the pancreas in nonhuman primates. Diabetes. 2014;63:2486-2497.Google Scholar
- 34.Gough SC, Bode B, Woo V, et al. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014;8587:70174-70173.Google Scholar
- 35.Seufert J, Gallwitz B. The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal, and central nervous systems. Diabetes Obes Metab. 2014;16:673-688.Google Scholar
- 36.Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36:843-854.Google Scholar
- 37.Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With AVE0010 (Lixisenatide) (ELIXA). http://clinicaltrials.gov/ct2/ show/NCT01147250. Accessed October 5, 2015.
- 38.Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus. http://clinicaltrials.gov/ct2/show/NCT01144338. Accessed October 5, 2015.
- 39.Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results - A Long Term Evaluation (LEADER®). http://clinicaltrials.gov/ct2/show/NCT01179048.
- 40.Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND). http:// clinicaltrials.gov/ct2/show/NCT01394952. Accessed October 5, 2015.Google Scholar
- 41.Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus. http://clinicaltrials.gov/ct2/show/NCT01720446. Accessed October 5, 2015.
- 42.Pfeffer MA. The evaluation of lixisenatide in acute coronary syndrome - the results of ELIXA. Results – cardiovascular outcomes. Webcast presentation at American Diabetes Association 75th Annual Scientific Sessions, June 5-9th, Boston, Massachusetts. http://professional.diabetes.org/Presentations_Details.aspx?session=4740. Accessed October 5, 2015.
- 43.Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013;62:2595-2604.Google Scholar
- 44.European Medicines Agengy (EMA). Investigation into GLP-1-based diabetes therapies concluded. www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/07/ news_detail_001856.jsp&mid=WC0b01ac058004d5c1. Accessed October 5, 2015.
- 45.Food and Drug Administration (FDA). FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. www.fda.gov/Drugs/DrugSafety/ucm343187.htm. Accessed October 5, 2015.
- 46.Li L, Shen J, Bala MM, et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ. 2014;348:g2366.Google Scholar
- 47.Meier JJ, Nauck MA. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia. 2014;57:1320-1324.Google Scholar