Download PDF
Diabetologie und Stoffwechsel 2007; 2(5): 315-320
DOI: 10.1055/s-2007-981274
Übersicht

© Georg Thieme Verlag Stuttgart · New York

Indikationsgebiete inkretinbasierter Therapien: Analyse von Studienpopulation, Studiendesign und Effektivität in Exenatide- und DDP-4-Inhibitor-Studien[*]

Indications for Incretin-based Therapies of Type 2 Diabetes: An Evaluation of Study Populations, Study Design and Effectiveness of Exenatide and DPP-4 Inhibitors in Clinical StudiesO. P. Bachmann1 , C. Kazda1 , B. Gallwitz2
  • 1Lilly Deutschland GmbH, Bad Homburg
  • 2Medizinische Klinik IV, Universität Tübingen
Further Information

Publication History

2007

2007

Publication Date:
03 September 2007 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Um die beiden neuen inkretinbasierten Therapieoptionen - DDP-4-Inhibitoren und das Inkretinmimetikum Exenatide - für die Behandlung des Diabetes mellitus Typ 2 besser einschätzen zu können, wurde in Ermangelung von direkten Vergleichsstudien ein indirekter Vergleich der vorliegenden publizierten klinischen Studien zu den DPP-4-Inhibitoren Sitagliptin und Vildagliptin sowie dem Inkretinmimetikum Exenatide durchgeführt. Eine Auswertung erfolgte hinsichtlich Studienpopulation, Studiendesign und Effektivität. Die DPP-4-Inhibitoren und Exenatide senken in den vorliegenden Studien den HbA1c effektiv. Die zunächst vergleichbar erscheinenden Effekte hinsichtlich HbA1c-Senkung relativieren sich bei Berücksichtung der oben genannten Auswertungskriterien. Es zeigten sich folgende qualitative Unterschiede: Exenatide war auch bei weitaus länger bestehendem Diabetes mellitus Typ 2 noch wirksam und senkte den HbA1c hier effektiver, und Exenatide hat den zusätzlichen Effekt der Gewichtsreduktion.

Abstract

In order to evaluate the two novel incretin based therapies for the treatment of type 2 diabetes, DPP-4 inhibitors and the incretin mimetic exenatide, the clinical studies published to date have been reviewed. Since head-to-head comparisons are lacking, the clinical studies published to date for the DPP-4 inhibitors sitagliptin and vildagliptin and for exenatide have been evaluated with respect to study population, study design and effectiveness. DPP-4 inhibitors and exenatide both effectively lowered the HbA1c in the available studies. Although HbA1c reductions look similar at the first look, they need to be put into perspective considering the above mentioned comparative criteria. The following qualitative differences can be identified: exenatide remained effective in patients with a markedly longer diabetes duration and lead to a greater HbA1c reduction in this patient group, and exenatide has the additional effect of allowing weight loss.

Schlüsselwörter

Inkretine - Inkretinmimetika - Exenatide - Sitagliptin - Vildagliptin - DPP-4-Inhibitoren - Typ-2-Diabetes

Key words

incretins - exenatide - incretin mimetics - sitagliptin - vildagliptin - DPP-4 inhibitors - type 2 diabetes

1 Unterstützt durch Eli Lilly and Company, Indianapolis, IN, USA und Amylin Pharmaceuticals, Inc., San Diego, CA, USA.

Literatur

  • 1 Barnett A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes.  Int J Clin Pract. 2006;  60 1454-1470
    CrossrefGoogle Scholar
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 Gallwitz B. Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data.  Int J Clin Pract. 2006;  60 1654-1661
    CrossrefGoogle Scholar
  • 4 Gallwitz B. Therapies for the treatment of type 2 diabetes mellitus based on incretin action.  Minerva Endocrinol. 2006;  31 133-147
    Google Scholar
  • 5 Mentlein R. Dipeptidyl-peptidase IV (CD 26) - role in the inactivation of regulatory peptides.  Regul Pept. 1999;  85 9-24
    CrossrefPubMedGoogle Scholar
  • 6 Gallwitz B. Sitagliptin: Profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes.  Drugs Today (Barc). 2007;  43 13-25
    CrossrefGoogle Scholar
  • 7 Ristic S, Bates P C. Vildagliptin: a novel DPP-4 inhibitor with pancreatic islet enhancement activity for treatment of patients with type 2 diabetes.  Drugs Today (Barc). 2006;  42 519-523
    CrossrefGoogle Scholar
  • 8 Goke R, Fehmann H C, Linn T, Schmidt H, Krause M, Eng J, Goke B. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells.  J Biol Chem. 1993;  268 19650-19655
    Google Scholar
  • 9 Lopez de Maturana R, Willshaw A, Kuntzsch A, Rudolph R, Donnelly D. The isolated N-terminal domain of the glucagon-like peptide-1 (GLP-1) receptor binds exendin peptides with much higher affinity than GLP-1.  J Biol Chem. 2003;  278 10195-10200
    CrossrefGoogle Scholar
  • 10 Aschner P, Kipnes M S, Lunceforf J K, Sanchez M, Mickel C, Williams-Herman D E. Effect of dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes.  Diabetes Care. 2006;  29 2632-2637
    CrossrefPubMedGoogle Scholar
  • 11 Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. 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
    CrossrefPubMedGoogle Scholar
  • 12 Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus.  Diabetologia. 2006;  49 2564-2571
    CrossrefPubMedGoogle Scholar
  • 13 Rosenstock J, Brazg R, Andryuk P J, Lu K, Stein P. 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
    CrossrefGoogle Scholar
  • 14 Bosi E, Camisasca R P, Collober C, Rochotte E, Garber A J. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin.  Diabetes Care. 2007;  30 890-895
    CrossrefGoogle Scholar
  • 15 Pi-Sunyer F X, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetes.  Diabetes Res Clin Pract. 2007;  76 132-138
    CrossrefPubMedGoogle Scholar
  • 16 Buse J B, Henry R R, Han J, Kim D D, Fineman M S, Baron A D. 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
    CrossrefPubMedGoogle Scholar
  • 17 DeFronzo R A, Ratner R E, Han J, Kim D D, Fineman M S, Baron A D. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in metformin-treated patients with type 2 diabetes.  Diabetes Care. 2005;  28 1092-1100
    CrossrefPubMedGoogle Scholar
  • 18 Kendall D M, Riddle M C, Rosenstock J, Zhuang D, Kim D D, Fineman M S, Baron A D. 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
    CrossrefPubMedGoogle Scholar
  • 19 Nauck M A, Meininger G, Sheng D, Terranella L, Stein P P. Sitagliptin Study 024 Group . 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
    CrossrefGoogle Scholar
  • 20 Rosenstock J, Baron M A, Camisasca R P, Cressier F, Couturier A, Dejager S. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.  Diabetes Obes Metab. 2007;  9 175-185
    CrossrefPubMedGoogle Scholar
  • 21 Rosenstock J, Baron M A, Dejager S, Mills D, Schweizer A. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24 week, double-blind, randomized trial.  Diabetes Care. 2007;  30 217-223
    CrossrefGoogle Scholar
  • 22 Heine R J, Van Gaal L F, Johns D, Mihm M J, Widel M H, Brodows R G. Exenatide versus insuline glargine in patients with suboptimally controlled Type 2 Diabetes.  Ann Int Med. 2005;  143 559-569
    CrossrefGoogle Scholar
  • 23 Nauck M A, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M. 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
    CrossrefGoogle Scholar
  • 24 Matthaei S, Häring H U. Behandlung des Diabetes mellitus Typ 2. DDG-Praxis-Leitlinie.  Diabetologie. 2007;  2 Suppl. 2 S 173-S 177
    Google Scholar

1 Unterstützt durch Eli Lilly and Company, Indianapolis, IN, USA und Amylin Pharmaceuticals, Inc., San Diego, CA, USA.

O. P. Bachmann

Saalburgstraße 153

61350 Bad Homburg

Phone: 0 61 72 / 2 73 27 06

Fax: 0 61 72 / 2 73 24 27

Email: bachmann_oliver@lilly.com

      >