Innovative Behandlungskonzepte des Typ–2–Diabetes – Optimierung der Blutzuckereinstellung und Reduktion des kardiovaskulären Risikos

Im Bereich der oralen Diabetestherapie, der Insulinpräparate und –applikationen sowie der Blutzuckerselbstkontrolle gab es in den vergangenen Jahren wesentliche Weiterentwicklungen. Trotz dieser Fortschritte ist bei einem großen Teil der Typ–2–Diabetiker der Blutzucker nur unzureichend eingestellt. Außerdem können die bisher verfügbaren oralen Antidiabetika den Diabetes weder heilen noch die Betazellfunktion oder den Stoffwechsel komplett wiederherstellen bzw. das kardiovaskuläre Risiko auf ein normales Maß reduzieren. Diese Defizite rechtfertigen die weitere Entwicklung innovativer Therapieoptionen. Zu den in den vergangenen Jahren neu entwickelten Strategien zählen vor allem die Nutzung des Inkretineffekts als Basis für neue Antidiabetika wie Inkretinmimetika, GLP–1–Analoga und DPP–4–Hemmer und die selektive Blockade von Rezeptoren des Endocannabinoidsystems.

Recent years have seen further major advances in the oral treatment of diabetes, insulins and their application, and in self–measurement of blood glucose levels. Nevertheless, glucose levels in a large number of type 2 diabetics are inadequately adjusted. Furthermore, the currently available oral antidiabetic agents are unable to effect a cure, completely restore beta cell function or metabolism, or even reduce the cardiovascular risk to normal levels. In view of these deficiencies, the further development of innovative therapeutic options is justified. Among the newly developed strategies of recent years, the utilisation of the incretin effect as a basis for new antidiabetics such as incretin mimetics, GLP–1 analogues and DPP–4 inhibitors, and the selective endocannabinoid receptor blockers deserves particular mention.

Key words

type 2 diabetes - beta cell function - cardiovascular risk - incretin effect - incretin mimetics - GLP–1 analogues - DPP–4 inhibitors - endogenous cannabinoid system

Literatur

• 1 Zimmet P. et al. . Global and societal implications of the diabetes epidemic.  Nature. 2001;  414 782-787
• 2 McCarthy MI.. Growing evidence for diabetes susceptibility genes from genome scan data.  Curr Diab Rep. 2003;  3 159-167
• 3 Rathmann W. et al. . High prevalence of undiagnosed diabetes mellitus in Southern Germany: target populations for efficient screening. The KORA survey 2000.  Diabetologia. 2003;  46 182-189
• 4 Icks A. et al. . Versorgungsqualität und Ausmaß von Komplikationen an einer bevölkerungsbezogenen Stichprobe von Typ–2–Diabetespatienten.  Dtsch Med Wochenschr. 2006;  131 73-78
• 5 Meier JJ. et al. . Neue Konzepte in der Behandlung des Typ–2–Diabetes.  Internist (Berl). 2007;  698 700-707
• 6 Blüher M. et al. . Adipositas und Metabolisches Syndrom.  Diabetologie. 2007;  3
• 7 Effect of intensive blood–glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.  Lancet. 1998;  352 854-865
• 8 Dormandy JA. et al. . Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.  Lancet. 2005;  366 1279-1289
• 9 Nauck MA. et al. . Gastric inhibitory polypeptide and glucagon–like peptide–1 in the pathogenesis of type 2 diabetes.  Diabetes. 2004;  53
• 10 Drucker DJ. et al. . The incretin system: glucagon–like peptide–1 receptor agonists and dipeptidyl peptidase–4 inhibitors in type 2 diabetes.  Lancet. 2006;  368 1696-1705
• 11 Pi–Sunyer FX. et al. . Efficacy and tolerability of vildagliptin monotherapy in drug–naive patients with type 2 diabetes.  Diabetes Res Clin Pract. 2007;  76 132-138
• 12 Bosi E. et al. . 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
• 13 Abel EL.. Cannabis: effects on hunger and thirst.  Behav Biol. 1975;  15 255-281
• 14 Pagotto U. et al. . The emerging role of the endocannabinoid system in endocrine regulation and energy balance.  Endocr Rev. 2006;  27 73-100
• 15 Munro S. et al. . Molecular characterization of a peripheral receptor for cannabinoids.  Nature. 1993;  365 61-65
• 16 Wierzbicki AS.. Rimonabant: endocannabinoid inhibition for the metabolic syndrome.  Int J Clin Pract. 2006;  60 1697-1706
• 17 Pi–Sunyer FX. et al. . Effect of rimonabant, a cannabinoid–1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO–North America: a randomized controlled trial.  JAMA. 2006;  295 761-775
• 18 Van Gaal LF. et al. . Effects of the cannabinoid–1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1–year experience from the RIO–Europe study.  Lancet. 2005;  365 1389-1397
• 19 Després JP. et al. . Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.  N Engl J Med. 2005;  353 2121-2134
• 20 Scheen AJ. et al. . Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study.  Lancet. 2006;  368 1660-1672
• 21 Nissen SE. et al. . Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial.  JAMA. 2008;  299 1547-1560
• 22 Questions and answers on the recommendation to suspend the marketing authorisation of Accomplia® (rimonabant), 23. Oktober 2008, www.emea.europa.eu/humandocs/PDFs/EPAR/acomplia/53715308en.pdf . EMEA.

1 KOoperative gesundheitsforschung in der Region Augsburg

2 United Kingdom Prospective Diabetes Study

3 STudies with Rimonabant And Tobacco Use

4 Rimonabant In Overweight/Obesity

Korrespondenz