Medikamentöse Diabetestherapie bei adipösen Patienten

Zusammenfassung

Empfehlungen zur Lebensstilmodifikation bilden die Basis aktueller Therapieempfehlungen bei Patienten mit Typ-2-Diabetes mellitus. Im Mittelpunkt steht zudem eine multifaktorielle, medikamentöse Therapiestrategie aller relevanter Risikofaktoren, um eine optimale Ereignisreduktion bei den Folgeerkrankungen zu erreichen. Bei der Therapie der Glukosestoffwechselstörung ist Metformin als Mittel der Wahl unumstritten, der Einsatz wird bereits bei Diagnosestellung empfohlen. Von den zusätzlich zur Verfügung stehenden antihyperglykämen Substanzen beleuchtet der Artikel jene Medikamente, die im Rahmen der Stoffwechseloptimierung ohne Gewichtszunahme und Hypoglykämiegefahr auskommen, nämlich Dipeptidylpeptidase 4-Inhibitoren, GLP1-Rezeptor-Agonisten und SGLT2-Inhibitoren. Alle Medikamente weisen ein günstiges kardiovaskuläres Risikoprofil auf. Für diese neueren, innovativen Substanzen stehen die Ergebnisse von Endpunktstudien jedoch noch aus.

Summary

Recommendations for lifestyle modification form the basis of current treatment recommendations for patients with type 2 diabetes mellitus. An additional focus is the multiple risk intervention with a drug strategy to optimally reduce the risk for the development of micro- and macrovascular vessel damage. In the treatment of hyperglycemia metformin is undisputed the first choice drug, the use is recommended already at diagnosis. Of the additionally available antihyperglycemic drugs the article highlights those substances which act without weight gain and without risk of hypoglycaemia, namely dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors. All drugs have a favorable cardiovascular risk profile. For these newer innovative substances, however, the results of outcome trials are still pending.

Schlüsselwörter

Typ-2-Diabetes mellitus - antihyperglykäme Therapie - GLP1-Agonisten - DPP4-Hemmer - SGLT2-Hemmer

Keywords

Type 2 diabetes mellitus - antihyperglycemic therapy - GLP1-agonists - DPP4-inhibitors - SGLT2-inhibitors

• Literatur

• 1 Bailey CJ, Gross JL, Pieters A. et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010; 375: 2223-2233.
• 2 Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574-579.
• 3 Bolinder J, Ljunggren O, Kullberg J. et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012; 97: 1020-1031.
• 4 Chan NN, Brain HP, Feher MD. Metformin-associated lactic acidosis: a rare or very rare clinical entity?. Diabetes Care 1998; 21: 1659-1663.
• 5 Derosa G, Maffioli P. Dipeptidyl Peptidase-4 Inhibitors: 3 Years of Experience. Diabetes Technol Ther 2012; Feb 10 [Epub ahead of print].
• 6 Faramarz IB, Moghissi E, Tiktin M. et al. Individualizing Glycemic Targets in Type 2 Diabetes Mellitus: Implications of Recent Clinical Trials. Ann Intern Med 2011; 154 (08) 554-559.
• 7 Fox CS, Pencina MJ, Wilson PW. et al. Lifetime risk of cardiovascular disease among individuals with and without diabetes stratified by obesity status in the Framingham heart study. Diabetes Care 2008; 31: 1582-1584.
• 8 Gæde P, Lund-Andersen H, Parving HH. et al. Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes. N Engl J Med 2008; 358: 580-591.
• 9 Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci 2011; 1243: 54-68.
• 10 Garber A, Duncan T, Goodman A. et al. Efficacy of metformin in type-II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med 1997; 102: 491-497.
• 11 Giorgino F, Leonardini A, Laviola L. Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials. Ann N Y Acad Sci 2013; 1281 (01) 36-50.
• 12 Henry RR, Murray AV, Marmolejo MH. et al. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract 2012; 66: 446-456.
• 13 Inzucchi SE, Bergenstal RM, Buse JB. et al. American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35 (06) 1364-1379.
• 14 Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 08 (12) 728-742.
• 15 Mottillo S, Filion KB, Genest J. et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010; 56 (14) 1113-1132.
• 16 Musso G, Gambino R, Cassader M. et al. A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med 2012; 44: 375-393.
• 17 Nauck MA, Del Prato S, Meier JJ. et al. Dapagliflozin versus Glipizide as Add-on Therapy in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin: A randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011; 34: 2015-2022.
• 18 Neumiller JJ. Differential chemistry (structure), mechanism of action, and pharmacology of GLP-1 receptor agonists and DPP-4 inhibitors. J Am Pharm Assoc 2009; 49 (Suppl. 01) S16-29.
• 19 Ptaszynska A, Johnsson KM, Apanovitch AM. et al. Safety of Dapagliflozin in Clinical Trials for T2DM. Diabetes 2012; 61 (01) 1011-P.
• 20 Rudofsky G, Rüssmann HJ, Siegmund T. SGLT2-Inhibition: Ein wirksames Therapieprinzip des Diabetes mellitus?. Dtsch Med Wochenschr 2013; 138: 1-7.
• 21 Wilding JP, Woo V, Soler NG. et al. Dapagliflozin 006 Study Group. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012; 156 (06) 405-415.
• 22 Yamaoka K, Tango T. Effects of lifestyle modification on metabolic syndrome: a systematic review and meta-analysis. BMC Medicine 2012; 10: 138.