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Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Review Article

GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus

Author(s): Lalita Dahiya*, Ramandeep Kaur, Rajiv Kumar, Manoj Kumar* and Kezia Palta

Volume 16, Issue 4, 2020

Page: [279 - 292] Pages: 14

DOI: 10.2174/1573399815666190502114924

Price: $65

Abstract

The rising epidemic of type 2 diabetes mellitus & associated complications is a serious cause of concern for humanity. Glucagon-like peptide-1 receptor agonists commonly abbreviated as GLP-1 RAs, emerged as a promising therapeutic class based on incretin therapy that regulates glucose metabolism through multiple mechanisms. In the present study, various investigational & clinically used GLP-1 RAs have been reviewed with emphasis on their efficacy, structural modifications, adverse effects and toxicities. Various clinical trials justifying their efficacy have also been included, which highlighted the potential of GLP-1 RAs over conventional anti hyperglycaemic agents through a study of pooled effect on glycemic efficacy and weight-loss. The significant potency and appreciable safety of GLP-1 RAs manifested their potential as a logical approach for the management of type 2 diabetes.

Keywords: Incretin, glucagon-like peptide-1, GLP-1 receptor agonists, dipeptidyl peptidase inhibitors, diabetes, insulin.

[1]
Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017; 128: 40-50.
[http://dx.doi.org/10.1016/j.diabres.2017.03.024] [PMID: 28437734]
[2]
Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94(3): 311-21.
[http://dx.doi.org/10.1016/j.diabres.2011.10.029] [PMID: 22079683]
[3]
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27(5): 1047-53.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[4]
De Block CEM, Van Gaal LF. GLP-1 receptor agonists for type 2 diabetes. Lancet 2009; 374(9683): 4-6.
[http://dx.doi.org/10.1016/S0140-6736(09)60942-9] [PMID: 19515414]
[5]
Marre M, Penfornis A. GLP-1 receptor agonists today. Diabetes Res Clin Pract 2011; 93(3): 317-27.
[http://dx.doi.org/10.1016/j.diabres.2011.01.004] [PMID: 21767888]
[6]
Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes: differences and similarities. Eur J Intern Med 2014; 25(5): 407-14.
[http://dx.doi.org/10.1016/j.ejim.2014.03.005] [PMID: 24694879]
[7]
Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)--preclinical and clinical results. Best Pract Res Clin Endocrinol Metab 2009; 23(4): 463-77.
[http://dx.doi.org/10.1016/j.beem.2009.03.008] [PMID: 19748064]
[8]
Kubo F, Miyatsuka T, Sasaki S, et al. Sustained expression of GLP-1 receptor differentially modulates β-cell functions in diabetic and nondiabetic mice. Biochem Biophys Res Commun 2016; 471(1): 68-74.
[http://dx.doi.org/10.1016/j.bbrc.2016.01.177] [PMID: 26854076]
[9]
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132(6): 2131-57.
[http://dx.doi.org/10.1053/j.gastro.2007.03.054] [PMID: 17498508]
[10]
Leech CA, Dzhura I, Chepurny OG, et al. Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic β cells. Prog Biophys Mol Biol 2011; 107(2): 236-47.
[http://dx.doi.org/10.1016/j.pbiomolbio.2011.07.005] [PMID: 21782840]
[11]
Hansotia T, Drucker DJ. GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. Regul Pept 2005; 128(2): 125-34.
[http://dx.doi.org/10.1016/j.regpep.2004.07.019] [PMID: 15780432]
[12]
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): 179-88.
[http://dx.doi.org/10.3109/10606820213687] [PMID: 12529935]
[13]
Chia CW, Egan JM. Biology and therapeutic potential of GLP-1 in the treatment of diabetes. Drug Discov Today Dis Mech 2005; 2(3): 295-01.
[http://dx.doi.org/10.1016/j.ddmec.2005.08.013]
[14]
Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol 2012; 166(1): 27-41.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01687] [PMID: 21950636]
[15]
Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin hormones: Similarities and differences. J Diabetes Investig 2010; 1(1-2): 8-23.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00022] [PMID: 24843404]
[16]
Gallwitz B, Witt M, Morys-Wortmann C, Fölsch UR, Schmidt WE. GLP-1/GIP chimeric peptides define the structural requirements for specific ligand-receptor interaction of GLP-1. Regul Pept 1996; 63(1): 17-22.
[http://dx.doi.org/10.1016/0167-0115(96)00019-5] [PMID: 8795084]
[17]
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007; 87(4): 1409-39.
[http://dx.doi.org/10.1152/physrev.00034.2006] [PMID: 17928588]
[18]
Rouillé Y, Kantengwa S, Irminger J-C, Halban PA. Role of the prohormone convertase PC3 in the processing of proglucagon to glucagon-like peptide 1. J Biol Chem 1997; 272(52): 32810-6.
[http://dx.doi.org/10.1074/jbc.272.52.32810] [PMID: 9407057]
[19]
Al-Sabah S, Donnelly D. The positive charge at Lys-288 of the glucagon-like peptide-1 (GLP-1) receptor is important for binding the N-terminus of peptide agonists. FEBS Lett 2003; 553(3): 342-6.
[http://dx.doi.org/10.1016/S0014-5793(03)01043-3] [PMID: 14572647]
[20]
Gautier JF, Fetita S, Sobngwi E, Salaün-Martin C. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab 2005; 31(3 Pt 1): 233-42.
[http://dx.doi.org/10.1016/S1262-3636(07)70190-8] [PMID: 16142014]
[21]
Lee Y-S, Jun H-S. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic β-cells. Metabolism 2014; 63(1): 9-19.
[http://dx.doi.org/10.1016/j.metabol.2013.09.010] [PMID: 24140094]
[22]
Siegel EG, Gallwitz B, Scharf G, et al. Biological activity of GLP-1-analogues with N-terminal modifications. Regul Pept 1999; 79(2-3): 93-102.
[http://dx.doi.org/10.1016/S0167-0115(98)00155-4] [PMID: 10100921]
[23]
Yin X, Wei D, Yi L, Tao X, Ma Y. Expression and purification of exendin-4, a GLP-1 receptor agonist, in Escherichia coli. Protein Expr Purif 2005; 41(2): 259-65.
[http://dx.doi.org/10.1016/j.pep.2004.10.014] [PMID: 15866711]
[24]
Arulmozhi DK, Portha B. GLP-1 based therapy for type 2 diabetes. Eur J Pharm Sci 2006; 28(1-2): 96-108.
[http://dx.doi.org/10.1016/j.ejps.2006.01.003] [PMID: 16488579]
[25]
Drugs@FDA: FDA Approved Drug Products. BYETTA (Exenatide) Available from: https://www.accessdata. fda.gov
[26]
Idris I, Patiag D, Gray S, Donnelly R. Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1. Biochem Pharmacol 2002; 63(5): 993-6.
[http://dx.doi.org/10.1016/S0006-2952(01)00924-8] [PMID: 11911852]
[27]
Gautier J-F, Choukem S-P, Girard J. Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes. Diabetes Metab 2008; 34(Suppl. 2): S65-72.
[http://dx.doi.org/10.1016/S1262-3636(08)73397-4] [PMID: 18640588]
[28]
Byetta package insert. Available from: http: //www.azpicentral.com/byetta/ byetta_med.pdf
[29]
van Genugten RE, van Raalte DH, Diamant M. Does glucagon-like peptide-1 receptor agonist therapy add value in the treatment of type 2 diabetes? Focus on exenatide. Diabetes Res Clin Pract 2009; 86(Suppl. 1): S26-34.
[http://dx.doi.org/10.1016/S0168-8227(09)70006-3] [PMID: 20115929]
[30]
Larsen PJ, Holst JJ. Glucagon-related peptide 1 (GLP-1): hormone and neurotransmitter. Regul Pept 2005; 128(2): 97-107.
[http://dx.doi.org/10.1016/j.regpep.2004.08.026] [PMID: 15780429]
[31]
Lovshin JA. Glucagon-like peptide-1 receptor agonists: a class update for treating type 2 diabetes. Can J Diabetes 2017; 41(5): 524-35.
[http://dx.doi.org/10.1016/j.jcjd.2017.08.242] [PMID: 28942790]
[32]
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 Care 2005; 28(5): 1092-100.
[http://dx.doi.org/10.2337/diacare.28.5.1092] [PMID: 15855572]
[33]
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): 259-67.
[http://dx.doi.org/10.1007/s00125-006-0510-2] [PMID: 17160407]
[34]
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): 604-6.
[http://dx.doi.org/10.2337/dc10-1900] [PMID: 21285388]
[35]
Kadowaki T, Namba M, Imaoka T, et al. Improved glycemic control and reduced bodyweight with exenatide: A double-blind, randomized, phase 3 study in Japanese patients with suboptimally weeks. 2 diabetes over 24 controlled type. J Diabetes Investig 2011; 2(3): 210-7.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00084.x] [PMID: 24843486]
[36]
Drugs@FDA: FDA Approved Drug Products VICTOZA (Liraglutide).Available from: https://www.accessdata. fda.gov
[37]
Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000; 43(9): 1664-9.
[http://dx.doi.org/10.1021/jm9909645] [PMID: 10794683]
[38]
Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context 2015; 4212283
[http://dx.doi.org/10.7573/dic.212283] [PMID: 26213556]
[39]
Lorenz M, Evers A, Wagner M. Recent progress and future options in the development of GLP-1 receptor agonists for the treatment of diabesity. Bioorg Med Chem Lett 2013; 23(14): 4011-8.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.022] [PMID: 23743288]
[40]
Ryan GJ, Foster KT, Jobe LJ. Review of the therapeutic uses of liraglutide. Clin Ther 2011; 33(7): 793-811.
[http://dx.doi.org/10.1016/j.clinthera.2011.06.004] [PMID: 21741090]
[41]
Rajeev SP, Wilding J. GLP-1 as a target for therapeutic intervention. Curr Opin Pharmacol 2016; 31: 44-9.
[http://dx.doi.org/10.1016/j.coph.2016.08.005] [PMID: 27591964]
[42]
Nauck MA. The design of the liraglutide clinical trial programme. Diabetes Obes Metab 2012; 14(2)(Suppl. 2): 4-12.
[http://dx.doi.org/10.1111/j.1463-1326.2012.01573] [PMID: 22405264]
[43]
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(9683): 39-47.
[http://dx.doi.org/10.1016/S0140-6736(09)60659-0] [PMID: 19515413]
[44]
Nauck M, Rizzo M, Johnson A, Bosch-Traberg H, Madsen J, Cariou B. Once-daily liraglutide versus lixisenatide as add-on to metformin in type 2 diabetes: A 26-week randomized controlled clinical trial. Diabetes Care 2016; 39(9): 1501-9.
[http://dx.doi.org/10.2337/dc15-2479] [PMID: 27311491]
[45]
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): 117-24.
[http://dx.doi.org/10.1016/S0140-6736(12)61267-7] [PMID: 23141817]
[46]
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(4): 289-97.
[http://dx.doi.org/10.1016/S2213-8587(13)70214-6] [PMID: 24703047]
[47]
Mathieu C, Rodbard HW, Cariou B, et al. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON). Diabetes Obes Metab 2014; 16(7): 636-44.
[http://dx.doi.org/10.1111/dom.12262] [PMID: 24443830]
[48]
Painter NA, Morello CM, Singh RF, McBane SE. An evidence-based and practical approach to using Bydureon™ in patients with type 2 diabetes. J Am Board Fam Med 2013; 26(2): 203-10.
[http://dx.doi.org/10.3122/jabfm.2013.02.120174] [PMID: 23471935]
[49]
Grimm M, Han J, Weaver C, et al. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med 2013; 125(3): 47-57.
[http://dx.doi.org/10.3810/pgm.2013.05.2660] [PMID: 23748506]
[50]
Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol 2014; 2(6): 464-73.
[http://dx.doi.org/10.1016/S2213-8587(14)70029-4] [PMID: 24731672]
[51]
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(9645): 1240-50.
[http://dx.doi.org/10.1016/S0140-6736(08)61206-4] [PMID: 18782641]
[52]
Traina AN, Lull ME, Hui AC, Zahorian TM, Lyons-Patterson J. Once-weekly exenatide as adjunct treatment of type 1 diabetes mellitus in patients receiving continuous subcutaneous insulin infusion therapy. Can J Diabetes 2014; 38(4): 269-72.
[http://dx.doi.org/10.1016/j.jcjd.2013.10.006] [PMID: 24797495]
[53]
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 open-label randomised trial. Lancet 2010; 375(9733): 2234-43.
[http://dx.doi.org/10.1016/S0140-6736(10)60406-0] [PMID: 20609969]
[54]
Drugs@FDA: FDA Approved Drugs TANZEUM (Albiglutide).Available from: http://www.accessdata.fda.gov
[55]
Ahrén B, Carr MC, Murphy K, et al. Albiglutide for the treatment of type 2 diabetes mellitus: An integrated safety analysis of the HARMONY phase 3 trials. Diabetes Res Clin Pract 2017; 126: 230-9.
[http://dx.doi.org/10.1016/j.diabres.2017.02.017] [PMID: 28284167]
[56]
Lindamood CA, Taylor JR. Emerging new therapies for the treatment of type 2 diabetes mellitus: glucagon-like peptide-1 receptor agonists. Clin Ther 2015; 37(3): 483-93.
[http://dx.doi.org/10.1016/j.clinthera.2015.01.003] [PMID: 25659912]
[57]
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(8): 2141-8.
[http://dx.doi.org/10.2337/dc14-0024] [PMID: 24898304]
[58]
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(8): 2317-25.
[http://dx.doi.org/10.2337/dc14-0001] [PMID: 24898300]
[59]
Jendle J, Grunberger G, Blevins T, Giorgino F, Hietpas RT, Botros FT. Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program. Diabetes Metab Res Rev 2016; 32(8): 776-90.
[http://dx.doi.org/10.1002/dmrr.2810] [PMID: 27102969]
[60]
Kanukala R, Likhar N, Mothe RK, Dang A. Efficacy and safety of dulaglutide in the management of type 2 diabetes mellitus: a meta- analysis of randomized controlled Trials. Value Health 2016; 19: A1-A18.
[http://dx.doi.org/10.1016/j.jval.2016.03.1319]
[61]
Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 2014; 37(8): 2149-58.
[http://dx.doi.org/10.2337/dc13-2761] [PMID: 24742660]
[62]
Blonde L, Jendle J, Gross J, et al. Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study. Lancet 2015; 385(9982): 2057-66.
[http://dx.doi.org/10.1016/S0140-6736(15)60936-9] [PMID: 26009229]
[63]
FDA approves Adlyxin to treat type 2 diabetes 2016. Available from: http: //www.fda.gov/newsevents/news-room/pressannounce-ments/ucm513602.htm
[64]
Werner U, Haschke G, Herling AW, Kramer W. Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes. Regul Pept 2010; 164(2-3): 58-64.
[http://dx.doi.org/10.1016/j.regpep.2010.05.008] [PMID: 20570597]
[65]
Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab 2013; 15(11): 1000-7.
[http://dx.doi.org/10.1111/dom.12121] [PMID: 23627775]
[66]
Yu Pan C, Han P, Liu X, et al. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev 2014; 30(8): 726-35.
[http://dx.doi.org/10.1002/dmrr.2541] [PMID: 24639432]
[67]
Van Gaal L, Souhami E, Zhou T, Aronson R. Efficacy and safety of the glucagon-like peptide-1 receptor agonist lixisenatide versus the dipeptidyl peptidase-4 inhibitor sitagliptin in young (<50 years) obese patients with type 2 diabetes mellitus. J Clin Transl Endocrinol 2014; 1(2): 31-7.
[http://dx.doi.org/10.1016/j.jcte.2014.03.001] [PMID: 29159080]
[68]
Bain SC. The clinical development program of lixisenatide: a once-daily glucagon-like Peptide-1 receptor agonist. Diabetes Ther 2014; 5(2): 367-83.
[http://dx.doi.org/10.1007/s13300-014-0073-z] [PMID: 25027491]
[69]
Porcellati F, Lucidi P, Bolli GB, Fanelli CG. GLP-1 RAs as compared to prandial insulin after failure of basal insulin in type 2 diabetes:Lessons from the 4B and Get-Goal DUO 2 trials. Diabetes Metab 2015. 41: 6S16-20.
[70]
Brown E, Cuthbertson DJ, Wilding JP. Newer GLP-1 receptor agonists and obesity-diabetes. Peptides 2018; 100: 61-7.
[http://dx.doi.org/10.1016/j.peptides.2017.12.009] [PMID: 29412833]
[71]
Lau J, Bloch P, Schäffer L, et al. The discovery of the once weekly glucagon like peptide 1 (GLP-1) analog semaglutide. J Med Chem 2015; 58(18): 7370-80.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00726] [PMID: 26308095]
[72]
Scheen AJ. Semaglutide: a promising new glucagon-like peptide-1 receptor agonist. Lancet Diabetes Endocrinol 2017; 5(4): 236-8.
[http://dx.doi.org/10.1016/S2213-8587(17)30012-8] [PMID: 28110912]
[74]
Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 2017; 5(4): 251-60.
[http://dx.doi.org/10.1016/S2213-8587(17)30013-X] [PMID: 28110911]
[75]
Scott LJ. Insulin Glargine/Lixisenatide: A review in type 2 diabetes. Drugs 2017; 77(12): 1353-62.
[http://dx.doi.org/10.1007/s40265-017-0783-4] [PMID: 28667587]
[76]
Henry RR, Rosenstock J, Logan DK, Alessi TR, Luskey K, Baron MA. Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes. Diabetes Care 2013; 36(9): 2559-65.
[http://dx.doi.org/10.2337/dc12-2410] [PMID: 23645886]
[77]
Tomlinson B, Hu M, Zhang Y, Chan P, Liu ZM. Investigational glucagon-like peptide-1 agonists for the treatment of obesity. Expert Opin Investig Drugs 2016; 25(10): 1167-79.
[http://dx.doi.org/10.1080/13543784.2016.1221925] [PMID: 27563838]
[78]
Filippatos TD, Panagiotopoulou TV, Elisaf MS. Adverse effects of GLP-1 receptor agonists. Rev Diabet Stud 2014; 11(3-4): 202-30.
[http://dx.doi.org/10.1900/RDS.2014.11.202] [PMID: 26177483]
[79]
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; 377(13): 1228-39.
[http://dx.doi.org/10.1056/NEJMoa1612917] [PMID: 28910237]
[80]
Pettus J, Hirsch I, Edelman S. GLP-1 agonists in type 1 diabetes. Clin Immunol 2013; 149(3): 317-23.
[http://dx.doi.org/10.1016/j.clim.2013.04.006] [PMID: 23643354]
[81]
Nauck MA, Friedrich N. Do GLP-1-based therapies increase cancer risk? Diabetes Care 2013; 36(Suppl. 2): S245-52.
[http://dx.doi.org/10.2337/dcS13-2004] [PMID: 23882053]
[82]
Cantini G, Mannucci E, Luconi M. Perspectives in GLP-1 research: new targets, new receptors. Trends Endocrinol Metab 2016; 27(6): 427-38.
[http://dx.doi.org/10.1016/j.tem.2016.03.017] [PMID: 27091492]
[83]
Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet 2014; 384(9961): 2228-34.
[http://dx.doi.org/10.1016/S0140-6736(14)61335-0] [PMID: 25220191]

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