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Diabetologie und Stoffwechsel 2008; 3(4): 234-240
DOI: 10.1055/s-2008-1076915
Originalarbeit

© Georg Thieme Verlag Stuttgart ˙ New York

Inkretinbasierte Antidiabetika im Vergleich: GLP-1-Mimetika und DPP-IV-Inhibitoren

Incretin-Based Antidiabetics: GLP-1 Mimetics and DPP-IV InhibitorsB. Gallwitz
  • 1Medizinische Klinik IV, Universität Tübingen
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Publication History

Publication Date:
07 August 2008 (online)

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Zusammenfassung

Die Behandlung des Typ-2-Diabetes ist bis heute eine Herausforderung. Trotz leitliniengerechter Behandlung erreichen nur etwa ein Drittel der Patienten eine optimale glykämische Kontrolle; andere wichtige Zielgrößen, wie die Gewichtsreduktion, werden oft nicht erreicht. Grundsätzlich ist keine der herkömmlichen Therapien in der Lage, die grundlegenden pathophysiologischen Defekte des Typ-2-Diabetes, nämlich die fortschreitende β-Zell-Dysfunktion und Insulinresistenz, aufzuhalten. Die neuen inkretinbasierten Therapien (GLP-1-Mimetika und DPP-IV-Hemmer) bieten durch ihre gute glykämische Kontrolle eine neue Alternative. Hervorzuheben ist das günstige Körpergewichtsprofil der GLP-1-Mimetika und ihr möglicher positiver Effekt auf die β-Zellfunktion. Die vorliegende Arbeit gibt eine aktuelle Übersicht zu diesen neuartigen GLP-1-basierten Therapien, mit Schwerpunkt auf Exenatide und Liraglutid aus der Substanzklasse der GLP-1-Mimetika.

Abstract

The effective management of type 2 diabetes mellitus continues to pose a challenge to physicians. Despite the use of treatments according to the guidelines, only one third of patients reach the optimal glycemic control target; other goals such as weight loss, often remain unaffected. None of the traditional treatments are able to delay the underlying pathophysiologic defects of type 2 diabetes, i. e. progressive ß-cell-dysfunction and insulin resistance. A new class of anti-diabetic drugs, the incretin-based therapies (GLP-1 mimetics and DPP-IV-inhibitors), provide an alternative option to currently available hypoglycaemic agents. Particular mention deserves the favourable weight-change profile of the GLP-1 mimetics and their potential β-cell regenerating effect. The present article reviews the profile of these new GLP-1-based therapies, focusing on the two GLP-1-mimetics exenatide and liraglutide.

Schlüsselwörter

Typ-2-Diabetes - Antidiabetika - Inkretine - GLP-1-Mimetika - DPP-IV-Inhibitoren

Key words

type 2 diabetes - antidiabetic drugs - incretins - GLP-1 mimetics - DPP-IV-inhibitors

Literatur

  • 1 Boyle P J, Freeman J S. Application of incretin mimetics and dipeptidyl peptidase IV inhibitors in managing type 2 diabetes mellitus.  J Am Osteopath Assoc. 2007;  107 (Suppl.) 10-16
    Search in Google Scholar
  • 2 Gaede P, Vedel P, Larsen N et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.  NEJM. 2003;  348 383-393
    Search in Google Scholar
  • 3 Gallwitz B. New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins.  Rev Diabetic Stud. 2005;  2 61-69
    CrossrefSearch in Google Scholar
  • 4 Drucker D J, Nauck M A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes.  Lancet. 2006;  368 1696-1705
    CrossrefPubMedSearch in Google Scholar
  • 5 MacDonald P E, El-kholy W, Riedel M J et al. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion.  Diabetes. 2002;  51 (Suppl. 3) 434-442
    CrossrefSearch in Google Scholar
  • 6 Turton M D, O'Shea D, Gunn I et al. A role for glucagon-like peptide-1 in the central regulation of feeding.  Nature. 1996;  379 69-72
    CrossrefSearch in Google Scholar
  • 7 Klonoff D C, Buse J B, Nielsen L L 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
    CrossrefSearch in Google Scholar
  • 8 Bulotta A, Farilla L, Hui H et al. The role of GLP-1 in the regulation of islet cell mass.  Cell Biochem Biophys. 2004;  40 (3 Suppl) 65-78
    CrossrefSearch in Google Scholar
  • 9 Rolin B, Larsen M O, Gotfredsen C F et al. The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases β-cell mass in diabetic mice.  Am J Physiol Endocrinol Metab. 2002;  283 E 745-E 752
    Search in Google Scholar
  • 10 Farilla L, Bulotta A, Hirshberg B et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets.  Endocrinology. 2003;  144 5149-5158
    CrossrefSearch in Google Scholar
  • 11 Drucker D J. Minireview: the glucagon-like peptides.  Endocrinology. 2001;  142 521-527
    CrossrefSearch in Google Scholar
  • 12 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
    CrossrefSearch in Google Scholar
  • 13 Gallwitz B. Liraglutide.  Drugs Future. 2008;  33 13-20
    CrossrefSearch in Google Scholar
  • 14 Edwards C M, Stanley S A, Davis R et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers.  Am J Physiol Endocrinol Metab. 2001;  281 E 155-E 161
    Search in Google Scholar
  • 15 Degn K, Juhl C, Sturis J et al. One week's treatment with the long-acting glucagon-like peptide-1 derivative Liraglutide (NN2211) markedly improves 24-h glycemia and α- and β-cell function and reduces endogenous glucose release in patients with type 2 diabetes.  Diabetes. 2004;  53 1187-1194
    CrossrefSearch in Google Scholar
  • 16 Jonker D, Toft A D, Kristensen P et al. Pharmacokinetic modelling of the once-daily human GLP-1 analogue Liraglutide in healthy volunteers and comparison to Exenatide.  Diabetes. 2007;  56 (Suppl. 1) A 160-A160
    Search in Google Scholar
  • 17 DeFronzo R A, Ratner R E, 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;  25 1092-1100
    Search in Google Scholar
  • 18 Buse J B, Henry R R, Han J H Exenatide-113 Clinical Study Group et al.,. Effects of exenatide (Exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes.  Diabetes Care. 2004;  27 2628-2635
    CrossrefPubMedSearch in Google Scholar
  • 19 Kendall D M, Riddle M C, 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;  28 1083-1091
    CrossrefPubMedSearch in Google Scholar
  • 20 Zinman B, Hoogwerf B J, Garcia S D et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes.  Ann Intern Med. 2007;  146 477-485
    Search in Google Scholar
  • 21 Heine R J, Van Gaal L F, Johns D GWAA Study Group et al.,. Exenatide versus insulin glargine in patients suboptimally controlled type 2 diabetes.  Ann Intern Med. 2005;  143 559-569
    CrossrefSearch in Google Scholar
  • 22 Nauck M A, 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;  50 259-267
    CrossrefSearch in Google Scholar
  • 23 Madsbad S, Schmitz O, Ranstam J et al. 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. 2004;  27 1335-1342
    CrossrefSearch in Google Scholar
  • 24 Harder H, Nielsen L, Thi T DT et al. The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes.  Diabetes Care. 2004;  27 1915-1921
    CrossrefSearch in Google Scholar
  • 25 Feinglos M N, Saad M F, Pi-Sunyer F X Liraglutide Dose-Response Study Group et al.,. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with type 2 diabetes.  Diabet Med. 2005;  22 1016-1023
    CrossrefSearch in Google Scholar
  • 26 Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long-acting human GLP-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes mellitus.  Diabetes Care. 2007;  30 1608-1610
    CrossrefSearch in Google Scholar
  • 27 Nauck M A, Hompesch M, Filipczak R et al. Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes.  Exp Clin Endocrinol Diabetes. 2006;  114 417-423
    Thieme ConnectSearch in Google Scholar
  • 28 Fehse F, Trautmann M, Holst J J et al. Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes.  J Clin Endocrinol Metab. 2005;  90 5991-5997
    CrossrefSearch in Google Scholar
  • 29 Mari A, Degn K, Brock B et al. Effects of the long-acting human Glucagon-like Peptide-1 Analog Liraglutide on β-cell function in normal living conditions.  Diabetes Care. 2007;  30 2032-2033
    CrossrefSearch in Google Scholar
  • 30 Amori R E, Lau J L, Pittas A G. Efficacy and safety of incretin therapy in type 2 diabetes.  JAMA. 2007;  298 194-206
    CrossrefPubMedSearch in Google Scholar
  • 31 Mest H J. Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetes via incretin enhancement.  Curr Opin Invest. 2006;  7 338-343
    Search in Google Scholar
  • 32 Raz I, Hanefeld M, Xu L Sitagliptin Study 023 Group et al.,. Efficacy and safety of the Dipeptidyl peptidase-4 inhibitor Sitagliptin as monotherapy in patients with type 2 diabetes mellitus.  Diabetologia. 2006;  49 2564-2571
    CrossrefPubMedSearch in Google Scholar
  • 33 Aschner P, Kipnes M S, Lunceford J K Sitagliptin Study 021 Group et al.,. Effect of the Dipeptidyl peptidase-4 inhibitor Sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes.  Diabetes Care. 2006;  29 2632-2637
    CrossrefPubMedSearch in Google Scholar
  • 34 Charbonnel B, Karasik A, Liu J et al. Sitagliptin Study 020 Group. Efficacy and safety of the Dipeptidyl peptidase-4 inhibitor Sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone.  Diabetes Care. 2006;  29 2638-2643
    CrossrefPubMedSearch in Google Scholar
  • 35 Rosenstock J, Brazg R, Andryuk P J. Sitagliptin Study 019 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.  Clin Ther. 2006;  28 1556-1568
    CrossrefSearch in Google Scholar
  • 36 Nauck M A, Meininger G, Sheng D Sitagliptin Study 024 Group et al.,. 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. 2007;  9 194-205
    CrossrefSearch in Google Scholar

Prof. Dr. med. B. Gallwitz

Medizinische Klinik und Poliklinik der Universität Tübingen · Abteilung Innere Medizin IV

Otfried-Müller-Str. 10

72076 Tübingen

Phone: +49 / 70 71 / 2 98 20 93

Fax: +49 / 70 71 / 29 50 04

Email: Baptist.Gallwitz@med.uni-tuebingen.de