Glukoseregulation der Niere und SGLT2-Inhibition – Neue therapeutische Optionen bei Diabetes mellitus

Die Niere ist ganz wesentlich an der Glukosehomöostase durch Glukoneogenese, Clearance und Degradation des zirkulierenden Insulins sowie die Rückresorption von Glukose aus dem Glomerulumfiltrat beteiligt. Diese Erkenntnisse haben dazu beigetragen, ein innovatives Therapiekonzept zur Reduktion der Blutglukose zu entwickeln. Dieses basiert auf der Inhibition der durch Natrium-abhängige Glukose-Co-Transporter-2 (SGLT-2 / sodium dependent glucose co-transporter-2) mediierten Glukoserückresorption in der Niere. Die umfangreichste publizierte Studienlage liegt für den SGLT2-Inhibitor Dapagliflozin vor, der seit kurzem auf dem deutschen Markt verfügbar ist. Mit Canagliflozin steht eine weitere Substanz kurz vor der Markteinführung, Empagliflozin wird im kommenden Jahr folgen. Die Substanzgruppe zeigt in den bisherigen Studien bei Typ-2-Diabetes eine HbA_1c-Senkung bei Gewichtsabnahme und geringer Hypoglykämiegefahr. In der klinischen Routine wird sich zeigen, ob die erhöhte Rate an Harnwegs- bzw. Genitalinfektionen ein generelles Problem darstellt. Die Glukoseausscheidung über den Harn bewirkt eine leichte osmotische Diurese. Ist ein Patient nicht Hypotonie- oder Hypovolämie-gefährdet, kann er durch die blutdrucksenkende Wirkung der SGLT2-Inhibition zusätzlich profitieren. Aufgrund der zum Teil unzureichenden Blutdruckeinstellung bei Personen mit Typ-2-Diabetes kann die blutdrucksenkende Wirkung der SGLT2-Inhibition, die sich in einigen Studien zeigte, zusätzlichen therapeutischen Nutzen bieten.

The kidney is involved in the glucose homoeostasis by regulating gluconeogenesis, clearance and degradation of circulating insulin, as well as reabsorption of glucose from the glomerular filtrate. Recent research findings have contributed to the development of an innovative therapeutic concept to reduce blood glucose levels based on the inhibition of SGLT-2 mediated glucose reabsorption in the kidney. The largest number of clinical studies is published for the SGLT-2 inhibitor dapagliflozin, that was introduced into the German market recently. Canagliflozin is the next product that will be launched, Empagliflozin will follow later. The SGLT-2 inhibitors show in the published trials a reduction of HbA_1c together with weight loss and a low risk of hypoglycaemia. The agent's use in the clinical routine will show whether the increased incidence of urinary tract infections and genital infections is a general problem. The elimination of glucose via the urine produces a slight degree of os-motic diuresis. Patients not at risk of hypotension or volume depletion may also draw an additional benefit from the antihypertensive effect produced by SGLT-2 inhibition. In persons with type 2 diabetes with inadequate blood-pressure control, the antihypertensive effect of SGLT2 inhibition shown in several studies may hence be an additional therapeutic benefit.

Key words

Diabetes - kidney - blood glucose level - SGLT2 inhibition

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