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GLP-1 Agonists and Dipeptidyl-Peptidase IV Inhibitors

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Diabetes - Perspectives in Drug Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 203))

Abstract

Novel therapeutic options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were introduced in 2005. Incretin-based therapies consist of two classes: (1) the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor and (2) dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) as oral medications raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In type 2 diabetes therapy, incretin-based therapies are attractive and more commonly used due to their action and safety profile. Stimulation of insulin secretion and inhibition of glucagon secretion by the above-mentioned agents occur in a glucose-dependent manner. Therefore, incretin-based therapies have no intrinsic risk for hypoglycemias. GLP-1 receptor agonists allow weight loss; DPP-4 inhibitors are weight neutral. This review gives an overview on the mechanism of action and the substances and clinical data available.

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References

  • Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M (2002) The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 45:195–202

    Article  CAS  PubMed  Google Scholar 

  • Ahmad SR, Swann J (2008) Exenatide and rare adverse events. N Engl J Med 358:1970–1971

    CAS  PubMed  Google Scholar 

  • Ahren B (2008a) Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs 13:593–607

    Article  CAS  PubMed  Google Scholar 

  • Ahren B (2008b) Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin. Vasc Health Risk Manag 4:383–394

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ahren B, Foley JE (2008) The islet enhancer vildagliptin: mechanisms of improved glucose metabolism. Int J Clin Pract Suppl 175:8–14

    Article  Google Scholar 

  • Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2457

    Article  CAS  PubMed  Google Scholar 

  • Barnett AH (2005) Exenatide. Drugs Today (Barc) 41:563–578

    Article  CAS  Google Scholar 

  • Barnett A (2007) Exenatide. Expert Opin Pharmacother 8:2593–2608

    Article  CAS  PubMed  Google Scholar 

  • Barnett AH (2009) New treatments in type 2 diabetes: a focus on the incretin-based therapies. Clin Endocrinol (Oxf) 70:343–353

    Article  CAS  Google Scholar 

  • Barnett AH, Burger J, Johns D, Brodows R, Kendall DM, Roberts A, Trautmann ME (2007) 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 29:2333–2348

    Article  CAS  PubMed  Google Scholar 

  • Brubaker PL, Drucker DJ (2004) Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 145:2653–2659

    Article  CAS  PubMed  Google Scholar 

  • Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ (2009) One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care 32:762–768

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD (2004) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27:2628–2635

    Article  CAS  PubMed  Google Scholar 

  • Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L (2009) 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 374:39–47

    Article  CAS  PubMed  Google Scholar 

  • Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R (2009) Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 63:1395–1406

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, Stein PP, Kaufman KD, Amatruda JM, Williams-Herman D (2008) Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 10:545–555

    Article  CAS  PubMed  Google Scholar 

  • Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, An B, Galecki A, Halter JB (2003) The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 52:1786–1791

    Article  CAS  PubMed  Google Scholar 

  • Courreges JP, Vilsboll T, Zdravkovic M, Le-Thi T, Krarup T, Schmitz O, Verhoeven R, Buganova I, Madsbad S (2008) Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with Type 2 diabetes. Diabet Med 25:1129–1131

    Article  PubMed Central  PubMed  Google Scholar 

  • Creutzfeldt W (1979) The incretin concept today. Diabetologia 16:75–85

    Article  CAS  PubMed  Google Scholar 

  • Creutzfeldt WO, Kleine N, Willms B, Orskov C, Holst JJ, Nauck MA (1996) Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients. Diabetes Care 19:580–586

    Article  CAS  PubMed  Google Scholar 

  • Cure P, Pileggi A, Alejandro R (2008) Exenatide and rare adverse events. N Engl J Med 358:1969–1970

    Article  CAS  PubMed  Google Scholar 

  • Deacon CF (2009) Potential of liraglutide in the treatment of patients with type 2 diabetes. Vasc Health Risk Manag 5:199–211

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Deacon CF, Holst JJ (2009) Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther 26:488–499

    Article  CAS  PubMed  Google Scholar 

  • DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD (2005) Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28:1092–1100

    Article  CAS  PubMed  Google Scholar 

  • DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS (2009) The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 32:1649–1655

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dore DD, Seeger JD, Arnold Chan K (2009) Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin 25:1019–1027

    Article  CAS  PubMed  Google Scholar 

  • Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705

    Article  CAS  PubMed  Google Scholar 

  • Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L (2008) Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 372:1240–1250

    Article  CAS  PubMed  Google Scholar 

  • Eng J, Kleinman WA, Singh L, Singh G, Raufman JP (1992) 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 267:7402–7405

    CAS  PubMed  Google Scholar 

  • Farilla L, Bulotta A, Hirshberg B, Li Calzi S, Khoury N, Noushmehr H, Bertolotto C, Di Mario U, Harlan DM, Perfetti R (2003) Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 144:5149–5158

    Article  CAS  PubMed  Google Scholar 

  • Fehmann HC, Habener JF (1992) Insulinotropic hormone glucagon-like peptide-I(7-37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. Endocrinology 130:159–166

    CAS  PubMed  Google Scholar 

  • Fonseca V, Baron M, Shao Q, Dejager S (2008) Sustained efficacy and reduced hypoglycemia during one year of treatment with vildagliptin added to insulin in patients with type 2 diabetes mellitus. Horm Metab Res 40:427–430

    Article  CAS  PubMed  Google Scholar 

  • Food and Drug Administration (FDA) (2009) Byetta (exenatide) – Renal Failure. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm188703.htm. 2 Nov 2009

  • Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393

    Article  PubMed  Google Scholar 

  • Gallwitz B (2006) Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data. Int J Clin Pract 60:1654–1661

    Article  CAS  PubMed  Google Scholar 

  • Gallwitz B (2008) Saxagliptin, a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. IDrugs 12:906–917

    Google Scholar 

  • Garber AJ, Spann SJ (2008) An overview of incretin clinical trials. J Fam Pract 57(Suppl):S10–S18

    PubMed  Google Scholar 

  • Garber A, Klein E, Bruce S, Sankoh S, Mohideen P (2006) Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Diabetes Obes Metab 8:156–163

    Article  CAS  PubMed  Google Scholar 

  • Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B (2008) Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 373:473–481

    Article  PubMed  Google Scholar 

  • Garber A, Henry RR, Ratner RE, Hale P, Chang CT, Bode B (2009) Monotherapy with Liraglutide, a Once-Daily Human GLP-1 analog, provides sustained reductions in A1C, FPG, and weight compared with Glimepiride in type 2 diabetes: LEAD-3 Mono 2-Year Results. Diabetes 58, Suppl 1: 162-OR

    Google Scholar 

  • Gedulin BR, Smith P, Prickett KS, Tryon M, Barnhill S, Reynolds J, Nielsen LL, Parkes DG, Young AA (2005) Dose-response for glycaemic and metabolic changes 28 days after single injection of long-acting release exenatide in diabetic fatty Zucker rats. Diabetologia 48:1380–1385

    Article  CAS  PubMed  Google Scholar 

  • Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559

    Article  CAS  PubMed  Google Scholar 

  • Green J, Feinglos M (2008) New combination treatments in the management of diabetes: focus on sitagliptin-metformin. Vasc Health Risk Manag 4:743–751

    PubMed Central  CAS  PubMed  Google Scholar 

  • Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG (2005) Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 143:559–569

    Article  CAS  PubMed  Google Scholar 

  • Heise T, Graefe-Mody EU, Huttner S, Ring A, Trommeshauser D, Dugi KA (2009) Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab 11:786–794

    Article  CAS  PubMed  Google Scholar 

  • Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA (2006a) Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol 45:876–886

    Article  Google Scholar 

  • Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P, Dietrich B, Golor G, Schrodter A, Keymeulen B, Lasseter KC, Kipnes MS, Snyder K, Hilliard D, Tanen M, Cilissen C, De Smet M, de Lepeleire I, Van Dyck K, Wang AQ, Zeng W, Davies MJ, Tanaka W, Holst JJ, Deacon CF, Gottesdiener KM, Wagner JA (2006b) Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab 91:4612–4619

    Article  CAS  PubMed  Google Scholar 

  • Herman GA, Bergman A, Yi B, Kipnes M (2006c) Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with type 2 diabetes. Curr Med Res Opin 22:1939–1947

    Article  CAS  PubMed  Google Scholar 

  • Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589

    Article  CAS  PubMed  Google Scholar 

  • International Diabetes Federation (IDF) (2009) Diabetes atlas. http://www.diabetesatlas.org

  • Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP (2008) Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 24:489–496

    Article  CAS  PubMed  Google Scholar 

  • Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD (2005) 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 28:1083–1091

    Article  CAS  PubMed  Google Scholar 

  • Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, Taylor K (2007) 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 30:1487–1493

    Article  CAS  PubMed  Google Scholar 

  • Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG (2008) 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 24:275–286

    CAS  PubMed  Google Scholar 

  • Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman MS, Baron AD (2005) Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm 62:173–181

    CAS  PubMed  Google Scholar 

  • Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M (2009) 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 31:806–815

    Article  CAS  PubMed  Google Scholar 

  • Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S (2009) 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 26:268–278

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Häring HU, Joost HG, Kellerer M, Kloos C, Kunt T, Nauck MA, Schernthaner G, Siegel E, Thienel F (2009) Medicinal antihyperglycemic therapy of type 2 diabetes. Guidelines of the German Diabetes Association. Exp Clin Endocrinol Diabetes 117:522–557

    Article  CAS  PubMed  Google Scholar 

  • McGill JB (2009) Insights from the Liraglutide Clinical Development Program – the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med 121:16–25

    Article  PubMed  Google Scholar 

  • Mest JH (2006) Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement. Curr Opin Investig Drugs 7:338–343

    CAS  PubMed  Google Scholar 

  • Müssig K, Oncu A, Lindauer P, Heininger A, Aebert H, Unertl K, Ziemer G, Häring HU, Holst JJ, Gallwitz B (2008) Effects of intravenous glucagon-like peptide-1 on glucose control and hemodynamics after coronary artery bypass surgery in patients with type 2 diabetes. Am J Cardiol 102:646–647

    Article  PubMed  Google Scholar 

  • Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B (2006) Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 49:1711–1721

    Article  CAS  PubMed  Google Scholar 

  • Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 32:193–203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • National Institute for Health and Clinical Excellence (2009) http://www.guidance.nice.org.uk/CG87

  • Nauck M, Marre M (2009) Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. Postgrad Med 121:5–15

    Article  PubMed  Google Scholar 

  • Nauck M, Stockmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–52

    Article  CAS  PubMed  Google Scholar 

  • Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W (1993a) Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301–307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W (1993b) Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36:741–744

    Article  CAS  PubMed  Google Scholar 

  • Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M (2007a) 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 50:259–267

    Article  CAS  PubMed  Google Scholar 

  • Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP (2007b) Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 9:194–205

    Article  CAS  PubMed  Google Scholar 

  • Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR (2009a) 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 32:84–90

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R (2009b) Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care 32:1237–1243

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP (2004) Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 110:955–961

    Article  CAS  PubMed  Google Scholar 

  • Nikolaidis LA, Doverspike A, Hentosz T, Zourelias L, Shen YT, Elahi D, Shannon RP (2005a) Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 312:303–308

    Article  CAS  PubMed  Google Scholar 

  • Nikolaidis LA, Elahi D, Shen YT, Shannon RP (2005b) Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289:H2401–H2408

    Article  CAS  PubMed  Google Scholar 

  • Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH (2007) Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 203:293–301

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pratley RE (2008) Overview of glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors for type 2 diabetes. Medscape J Med 10:171

    PubMed Central  PubMed  Google Scholar 

  • Pratley RE, Rosenstock J, Pi-Sunyer FX, Banerji MA, Schweizer A, Couturier A, Dejager S (2007) Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care 30:3017–3022

    Article  CAS  PubMed  Google Scholar 

  • Pratley RE, Reusch JE, Fleck PR, Wilson CA, Mekki Q (2009) Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 25:2361–2371

    Article  CAS  PubMed  Google Scholar 

  • Raman VS, Heptulla RA (2009) New potential adjuncts to treatment of children with type 1 diabetes mellitus. Pediatr Res 65:370–374

    Article  CAS  PubMed  Google Scholar 

  • Retterstol K (2009) Taspoglutide: a long acting human glucagon-like polypeptide-1 analogue. Expert Opin Investig Drugs 18:1405–1411

    Article  CAS  PubMed  Google Scholar 

  • Rosenstock J, Sankoh S, List JF (2008) Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 10:376–386

    Article  CAS  PubMed  Google Scholar 

  • Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R (2009a) Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 25:2401–2411

    Article  CAS  PubMed  Google Scholar 

  • Rosenstock J, Reusch J, Bush M, Yang F, Stewart M (2009b) The 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 32:1880–1886

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Scott R, Wu M, Sanchez M, Stein P (2007) Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract 61:171–180

    Article  CAS  PubMed  Google Scholar 

  • Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP (2006) Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12:694–699

    Article  CAS  PubMed  Google Scholar 

  • Sturis J, Gotfredsen CF, Romer J, Rolin B, Ribel U, Brand CL, Wilken M, Wassermann K, Deacon CF, Carr RD, Knudsen LB (2003) GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on beta-cell mass dynamics. Br J Pharmacol 140:123–132

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tahrani AA, Piya MK, Barnett AH (2009) Saxagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Adv Ther 26:249–262

    Article  CAS  PubMed  Google Scholar 

  • Vilsboll T (2009) Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc) 45:101–113

    Article  Google Scholar 

  • Vilsboll T, Brock B, Perrild H, Levin K, Lervang HH, Kolendorf K, Krarup T, Schmitz O, Zdravkovic M, Le-Thi T, Madsbad S (2008) 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 25:152–156

    Article  CAS  PubMed  Google Scholar 

  • Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Ling Y, Meehan AG, Katz L, Engel SS, Kaufman KD, Amatruda JM (2009) Sitagliptin, a selective DPP-4 inhibitor, improves glycemic control when added to insulin, with or without Metformin, in patients with type 2. Diabetes 58(Suppl 1):588

    Google Scholar 

  • Vollmer K, Gardiwal H, Menge BA, Goetze O, Deacon CF, Schmidt WE, Holst JJ, Meier JJ (2009) Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans. J Clin Endocrinol Metab 94:1379–1385

    Article  CAS  PubMed  Google Scholar 

  • Waldron-Lynch F, von Herrath M, Herold KC (2008) Towards a curative therapy in type 1 diabetes: remission of autoimmunity, maintenance and augmentation of beta cell mass. Novartis Found Symp 292:146–155

    Article  CAS  PubMed  Google Scholar 

  • Wellendorph P, Johansen LD, Brauner-Osborne H (2009) Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients. Mol Pharmacol 76:453–465

    Article  CAS  PubMed  Google Scholar 

  • Werner U (2008) Preclinical pharmacology of the new GLP-1 receptor agonist AVE0010. Ann Endocrinol (Paris) 69:164–165

    Article  CAS  Google Scholar 

  • Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Williams-Herman D, Round E, Swern AS, Musser B, Davies MJ, Stein PP, Kaufman KD, Amatruda JM (2008) Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord 8:14

    Article  PubMed Central  PubMed  Google Scholar 

  • Wolf R, Frederich R, Fiedorek FT, Donovan M, Xu Z, Harris S, Chen R (2009) Evaluation of CV risk in the Saxagliptin clinical trials. Diabetes 59(Suppl 1):8-LB

    Google Scholar 

  • Yang J, Campitelli J, Hu G, Lin Y, Luo J, Xue C (2007) Increase in DPP-IV in the intestine, liver and kidney of the rat treated with high fat diet and streptozotocin. Life Sci 81:272–279

    Article  CAS  PubMed  Google Scholar 

  • Yoo BK, Triller DM, Yoo DJ (2006) Exenatide: a new option for the treatment of type 2 diabetes. Ann Pharmacother 40:1777–1784

    Article  CAS  PubMed  Google Scholar 

  • Zeitler P (2009) Update on nonautoimmune diabetes in children. J Clin Endocrinol Metab 94:2215–2220

    Article  CAS  PubMed  Google Scholar 

  • Zinman B, Hoogwerf BJ, Duran Garcia S, Milton DR, Giaconia JM, Kim DD, Trautmann ME, Brodows RG (2007) The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 146:477–485

    Article  PubMed  Google Scholar 

  • Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L (2009) 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 32:1224–1230

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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  1. Medizinische Klinik IV, Otfried-Müller-Str. 10, 72076, Tübingen, Germany

    Baptist Gallwitz

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  1. Baptist Gallwitz
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Correspondence to Baptist Gallwitz .

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  1. Fakultät Lebenswissenschaften Molekulare Pharmakologie und Toxikologie, Technische Universität Braunschweig, Beethovenstraße 55, 38106, Braunschweig, Germany

    Mathias Schwanstecher

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Gallwitz, B. (2011). GLP-1 Agonists and Dipeptidyl-Peptidase IV Inhibitors. In: Schwanstecher, M. (eds) Diabetes - Perspectives in Drug Therapy. Handbook of Experimental Pharmacology, vol 203. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17214-4_3

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