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Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review

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Pages 241-265 | Received 03 Jul 2015, Accepted 16 Nov 2015, Published online: 08 Jan 2016

References

  • American Diabetes Association. 7. Approaches to glycemic treatment. Diabetes Care. 2015 Jan 1;38(Suppl 1):S41–S48.
  • 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.
  • Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409–1439.
  • Deacon CF. Circulation and degradation of GIP and GLP-1. Horm Metab Res. 2004 Dec;36(1112):761–765.
  • Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard lecture, 2005. Diabetologia. 2006 Feb;49(2):253–260.
  • Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012 Sep 4;8(12):728–742.
  • Madsbad S, Kielgast U, Asmar M, et al. 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 May;13(5):394–407.
  • Harris KB, McCarty DJ. Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2015 Feb 1;6(1):3–18.
  • 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 Feb 15;117(2):77–88.
  • Kielgast U, Holst JJ, Madsbad S. Treatment of type 1 diabetic patients with glucagon-like peptide-1 (GLP-1) and GLP-1R agonists. Curr Diabetes Rev. 2009 Nov;5(4):266–275.
  • Cho YM, Wideman RD, Kieffer TJ. Clinical application of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus. Endocrinol Metab (Seoul). 2013 Dec;28(4):262–274.
  • Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.
  • 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 Nov;27(11):2628–2635.
  • Zinman B, Hoogwerf BJ, Durán García S, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007 Apr 3;146(7):477–485.
  • 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 May;28(5):1092–1100.
  • 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 Care. 2005 May;28(5):1083–1091.
  • Moretto TJ, Milton DR, Ridge TD, et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2008 Aug;30(8):1448–1460.
  • Kadowaki T, Namba M, Yamamura A, et al. Exenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes. Endocr J. 2009;56(3):415–424.
  • Gao Y, Yoon KH, Chuang L-M, et al. Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a sulphonylurea. Diabetes Res Clin Pract. 2009 Jan;83(1):69–76.
  • Liutkus J, Rosas Guzman J, Norwood P, et al. A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin. Diabetes Obes Metab. 2010 Dec;12(12):1058–1065.
  • Apovian CM, Bergenstal RM, Cuddihy RM, et al. Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. Am J Med. 2010;123(5):468.e9–17.
  • Buse JB, Bergenstal RM, Glass LC, et al. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011 Jan 18;154(2):103–112.
  • Derosa G, Franzetti IG, Querci F, et al. Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes. Diabet Med J Br Diabet Assoc. 2012 Dec;29(12):1515–1523.
  • Lu C-H, Wu T-J, Shih K-C, et al. Safety and efficacy of twice-daily exenatide in Taiwanese patients with inadequately controlled type 2 diabetes mellitus. J Formos Med Assoc Taiwan Yi Zhi. 2013 Mar;112(3):144–150.
  • 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 Oct 18;143(8):559–569.
  • 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 Feb;50(2):259–267.
  • Davis SN, Johns D, Maggs D, et al. Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents. Diabetes Care. 2007 Nov;30(11):2767–2772.
  • 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 Jan;25(1):65–75.
  • 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 Dec;11(12):1153–1162.
  • Bunck MC, Diamant M, Corner A, et al. One-year treatment with exenatide improves cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009 May 1;32(5):762–768.
  • 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 Mar;34(3):604–606.
  • Xu W, Bi Y, Sun Z, et al. Comparison of the effects on glycaemic control and β-cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel-group trial (the CONFIDENCE study). J Intern Med. 2015 Jan;277(1):137–150.
  • Derosa G, Maffioli P, Salvadeo SAT, et al. Exenatide versus glibenclamide in patients with diabetes. Diabetes Technol Ther. 2010 Mar;12(3):233–240.
  • 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 Sep;666(13):251–256.
  • 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 Jun 16;379(9833):2270–2278.
  • Bunck MC, Cornér A, Eliasson B, et al. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis. 2010;212(1):223–229.
  • Eng C, Kramer CK, Zinman B, et al. 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. 2014Dec 20;384(9961):2228–2234.
  • 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 J Br Diabet Assoc. 2010Sep;27(9):1024–1032.
  • Lund A, Knop F, Vilsbøll T. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes: differences and similarities. Eur J Intern Med. 2014 Mar;25(5):407–414.
  • Fonseca VA, Alvarado-Ruiz R, Raccah D, et al. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012 Jun;35(6):1225–1231.
  • Pinget M, Goldenberg R, Niemoeller E, et al. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013 Nov;15(11):1000–1007.
  • Ahrén B, Leguizamo Dimas A, Miossec P, et al. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). Diabetes Care. 2013 Sep;36(9):2543–2550.
  • Rosenstock J, Hanefeld M, Shamanna P, et al. Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). J Diabetes Complications. 2014 Jun;28(3):386–392.
  • Seino Y, Min KW, Niemoeller E, et al. EFC10887 GETGOAL-L Asia Study Investigators. Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). Diabetes Obes Metab. 2012Oct;14(10):910–917.
  • Riddle MC, Aronson R, Home P, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care. 2013 Sep;36(9):2489–2496.
  • Riddle MC, Forst T, Aronson R, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1). Diabetes Care. 2013 Sep;36(9):2497–2503.
  • Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther. 2009 Nov;31(11):2472–2488.
  • Agersø H, Jensen LB, Elbrønd B, et al. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002 Feb;45(2):195–202.
  • Marre M, Shaw J, Brändle M, et al. 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 J Br Diabet Assoc. 2009 Mar;26(3):268–278.
  • Nauck M, Frid A, Hermansen K, et al. 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 Jan;32(1):84–90.
  • Zinman B, Gerich J, Buse JB, et al. 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):1224–1230.
  • Russell-Jones D, Vaag A, Schmitz O, et al. 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 Oct;52(10):2046–2055.
  • Forst T, Michelson G, Ratter F, et al. Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet Med J Br Diabet Assoc. 2012;29(9):1115–1118.
  • De Wit HM, Vervoort GMM, Jansen HJ, et al. Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT). Diabetologia. 2014 Sep;57(9):1812–1819.
  • Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 Feb 7;373(9662):473–481.
  • Seino Y, Rasmussen MF, Nishida T, et al. Efficacy and safety of the once-daily human GLP-1 analogue, liraglutide, vs glibenclamide monotherapy in Japanese patients with type 2 diabetes. Curr Med Res Opin. 2010 May;26(5):1013–1022.
  • Li C, Li J, Zhang Q, et al. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity. Cardiovasc Diabetol. 2012;11:142.
  • 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 Apr 24;375(9724):1447–1456.
  • Yang W, Chen L, Ji Q, et al. Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*). Diabetes Obes Metab. 2011 Jan;13(1):81–88.
  • Charbonnel B, Steinberg H, Eymard E, et al. Efficacy and safety over 26 weeks of an oral treatment strategy including sitagliptin compared with an injectable treatment strategy with liraglutide in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomised clinical trial. Diabetologia. 2013 Jul;56(7):1503–1511.
  • 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 Jul;16(7):636–644.
  • Brady EM, Davies MJ, Gray LJ, et al. A randomized controlled trial comparing the GLP-1 receptor agonist liraglutide to a sulphonylurea as add on to metformin in patients with established type 2 diabetes during Ramadan: the Treat 4 Ramadan Trial. Diabetes Obes Metab. 2014;16(6):527–536.
  • Kaku K, Rasmussen MF, Clauson P, et al. Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes. Diabetes Obes Metab. 2010 Apr;12(4):341–347.
  • Vilsbøll T, Zdravkovic M, Le-Thi T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care. 2007 Jun;30(6):1608–1610.
  • Seino Y, Rasmussen MF, Zdravkovic M, et al. Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: A double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2008 Aug;81(2):161–168.
  • Madsbad S, Schmitz O, Ranstam J, et al. NN2211-1310 International Study Group. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care. 2004Jun;27(6):1335–1342.
  • Feinglos MN, Saad MF, Pi-Sunyer FX, et al. Liraglutide Dose-Response Study Group. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes. Diabet Med J Br Diabet Assoc. 2005Aug;22(8):1016–1023.
  • Vilsbøll T, Brock B, Perrild H, et al. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med J Br Diabet Assoc. 2008 Feb;25(2):152–156.
  • Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open. 2013;3(1):e001986.
  • Hermansen K, Bækdal TA, Düring M, et al. Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial. Diabetes Obes Metab. 2013 Nov;15(11):1040–1048.
  • Mann KV, Raskin P. Exenatide extended-release: a once weekly treatment for patients with type 2 diabetes. Diabetes Metab Syndr Obes Targets Ther. 2014;7:229–239.
  • 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 Oct 4;372(9645):1240–1250.
  • 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 Jun 26;375(9733):2234–2243.
  • Inagaki N, Atsumi Y, Oura T, et al. Efficacy and safety profile of exenatide once weekly compared with insulin once daily in Japanese patients with type 2 diabetes treated with oral antidiabetes drug(s): results from a 26-week, randomized, open-label, parallel-group, multicenter, noninferiority study. Clin Ther. 2012 Sep;34(9):1892–908.e1.
  • Davies M, Heller S, Sreenan S, et al. Once-weekly exenatide versus once- or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas. Diabetes Care. 2013 May;36(5):1368–1376.
  • Bergenstal RM, Wysham C, Macconell L, et al. 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 Aug 7;376(9739):431–439.
  • Russell-Jones D, Cuddihy RM, Hanefeld M, et al. 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 Feb;35(2):252–258.
  • 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 Feb;17(2):179–187.
  • Madsbad S. The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications. Diabetes Obes Metab. 2014 Jan;16(1):9–21.
  • Baggio LL, Huang Q, Brown TJ, et al. A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes. 2004 Sep;53(9):2492–2500.
  • Woodward HN, Anderson SL. Once-weekly albiglutide in the management of type 2 diabetes: patient considerations. Patient Prefer Adherence. 2014;8:789–803.
  • Blair HA, Keating GM Albiglutide: A review of its use in patients with type 2 diabetes mellitus. Drugs. [Internet]. 2015 Mar 17; [cited 2015 Apr 11]. Available from: http://link.springer.com/10.1007/s40265-015-0370-5.
  • Rosenstock J, Reusch J, Bush M, et al. Albiglutide Study Group. Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care. 2009Oct;32(10):1880–1886.
  • Reinhardt R, Nauck MA, Stewart M, et al. HARMONY 2 results at week 52 primary endpoint: once-weekly albiglutide monotherapy for patients with type 2 diabetes mellitus inadequately controlled with diet and exercise [Abstract no. 903]. 49th Annual Meeting of the European Association for the study of diabetes; 2013 Sep 23–27; Barcelona.
  • 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 Dec;16(12):1257–1264.
  • Seino Y, Inagaki N, Miyahara H, et al. A randomized dose-finding study demonstrating the efficacy and tolerability of albiglutide in Japanese patients with type 2 diabetes mellitus. Curr Med Res Opin. 2014;30(6):1095–1106.
  • 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 Aug;37(8):2141–2148.
  • 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 Dec;57(12):2475–2484.
  • Leiter LA, Carr MC, Stewart M, et al. Efficacy and safety of the once-weekly GLP-1 receptor agonist albiglutide versus sitagliptin in patients with type 2 diabetes and renal impairment: a randomized phase III study. Diabetes Care. 2014 Aug;37(10):2723–2730.
  • Rosenstock J, Reusch J, Bush M, et al. Albiglutide Study Group. Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care. 2009Oct;32(10):1880–1886.
  • 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 Aug;37(8):2317–2325.
  • Thompson AM, Trujillo JM. Dulaglutide: the newest glp-1 receptor agonist for the management of type 2 diabetes. Ann Pharmacother. 2015 Mar 1;49 (3):351–359.
  • Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care. 2014 Aug;37(8):2159–2167.
  • Umpierrez GE, Blevins T, Rosenstock J, et al. The effects of LY2189265, a long-acting glucagon-like peptide-1 analogue, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: the EGO study. Diabetes Obes Metab. 2011 May;13(5):418–425.
  • Grunberger G, Chang A, Garcia Soria G, et al. Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study. Diabet Med J Br Diabet Assoc. 2012 Oct;29(10):1260–1267.
  • Terauchi Y, Satoi Y, Takeuchi M, et al. Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study. Endocr J. 2014;61(10):949–959.
  • Nauck M, Weinstock RS, Umpierrez GE, et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care. 2014 Aug;37(8):2149–2158.
  • Umpierrez G, Tofé Povedano S, Pérez Manghi F, et al. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care. 2014 Aug;37(8):2168–2176.
  • Giorgino F, Benroubi M, Sun J-H, et al. Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care. 2015 Dec;38(12):2241–2249.
  • 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 May 23;385(9982):2057–2066.
  • 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 Oct 11;384(9951):1349–1357.
  • 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 May;96(5):1301–1310.
  • 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 Jul 4;374(9683):39–47.
  • 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 Jan 12;381(9861):117–124.
  • 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 Apr;2(4):289–297.
  • 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 Oct;36(10):2945–2951.
  • Kapitza C, Forst T, Coester H-V, 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 Jul;15(7):642–649.
  • Fineman MS, Cirincione BB, Maggs D, et al. GLP-1 based therapies: differential effects on fasting and postprandial glucose. Diabetes Obes Metab. 2012 Aug;14(8):675–688.
  • Madsbad S. Treatment of type 2 diabetes with incretin-based therapies. Lancet. 2009 Feb 7;373(9662):438–439.
  • Nauck MA, Kemmeries G, Holst JJ, et al. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes. 2011 May;60(5):1561–1565.
  • Umapathysivam MM, Lee MY, Jones KL, et al. Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia. Diabetes. 2014 Feb 1;63(2):785–790.
  • Marathe CS, Rayner CK, Jones KL, et al. Relationships between gastric emptying, postprandial glycemia, and incretin hormones. Diabetes Care. 2013;36(5):1396–1405.
  • Jones AG, McDonald TJ, Shields BM, et al. Markers of β-cell failure predict poor glycemic response to glp-1 receptor agonist therapy in type 2 diabetes. Diabetes Care. 2015 Aug 4. pii: dc150258. [Epub ahead of print].
  • Meier JJ, Rosenstock J, Hincelin-Méry A, et al. Contrasting effects of lixisenatide and liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 diabetes on optimized insulin glargine with or without metformin: a randomized, open-label trial. Diabetes Care. 2015;38(7):1263–1273.
  • Monnier L, Colette C, Owens D. Postprandial and basal glucose in type 2 diabetes: assessment and respective impacts. Diabetes Technol Ther. 2011 Jun;13(S1):S – 25 – S – 32.
  • Horowitz M, Vilsbøll T, Zdravkovic M, et al. Patient-reported rating of gastrointestinal adverse effects during treatment of type 2 diabetes with the once-daily human GLP-1 analogue, liraglutide. Diabetes Obes Metab. 2008 Jul;10(7):593–596.
  • Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs–FDA and EMA assessment. N Engl J Med. 2014 Feb 27;370(9):794–797.
  • Monami M, Dicembrini I, Nardini C, et al. Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials. Diabetes Res Clin Pract. 2014 Feb;103(2):269–275.
  • Meier JJ, Nauck MA. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia. 2014 Jul;57(7):1320–1324.
  • Nauck MA, Friedrich N. Do GLP-1-based therapies increase cancer risk? Diabetes Care. 2013 Aug;36(Suppl 2):S245–S252.
  • Butler PC, Elashoff M, Elashoff R, et al. A critical analysis of the clinical use of incretin-based therapies: Are the GLP-1 therapies safe? Diabetes Care. 2013 Jul;36(7):2118–2125.
  • Suarez EA, Koro CE, Christian JB, et al. Incretin-mimetic therapies and pancreatic disease: a review of observational data. Curr Med Res Opin. 2014 Dec;30(12):2471–2481.
  • Ferdinand KC, White WB, Calhoun DA, et al. Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus. Hypertension. 2014 Oct;64(4):731–737.
  • Pyke C, Heller RS, Kirk RK, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014 Apr;155(4):1280–1290.
  • No CV benefit with lixisenatide in ELIXA, but results reassure [Internet]. Medscape. [ cited 2015 Sep 16]. Available from: http://www.medscape.com/viewarticle/846074.
  • Meier JJ, Nauck MA. Incretin-based therapies: where will we be 50 years from now? Diabetologia. 2015 Aug;58(8):1745–1750.
  • Gough SCL, 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 Nov;2(11):885–893.
  • Buse JB, Vilsbøll T, Thurman J, et al. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014 Nov;37(11):2926–2933.
  • Barnett AH. Complementing insulin therapy to achieve glycemic control. Adv Ther. 2013 Jun;30(6):557–576.
  • Dirksen C, Bojsen-Møller KN, Jørgensen NB, et al. Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass. Diabetologia. 2013 Dec;56(12):2679–2687.
  • Hjøllund KR, Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs. Diabetologia. 2011 Aug;54(8):2206–2208.
  • Marbury T, Flint A, Segel S, et al. Pharmacokinetics and tolerability of a single dose of semaglutide, a once-weekly human GLP-1 analog, in subjects with and without renal impairment. [Abstract no. 882]. 50th Annual Meeting of the European Association for the Study of Diabetes; 2013 Sep 16–19; Vienna.
  • 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.
  • 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 Jun;28(3):393–398.
  • Day JW, Gelfanov V, Smiley D, et al. Optimization of co-agonism at GLP-1 and glucagon receptors to safely maximize weight reduction in DIO-rodents. Biopolymers. 2012;98(5):443–450.
  • De Silva A, Salem V, Long CJ, et al. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab. 2011 Nov 2;14(5):700–706.

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