Kardiovaskuläre Studien-Endpunkte bei Typ-2-Diabetes und die Sulfonylharnstoff-Kontroverse

 

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Zusammenfassung

Sulfonylharnstoffe (SH) sind häufig verwendete glukosesenkende Therapeutika für Patienten mit Typ-2-Diabetes-mellitus (T2DM). In Bezug auf kardiovaskuläre Effekte dieser Substanzen zeigen Beobachtungs- und Registerstudien divergierende und zum Teil widersprüchliche Ergebnisse. Die vorliegende Arbeit analysierte den Einfluss von SH auf kardiovaskuläre Endpunkte in längerfristigen randomisierten Studien mit aktivem Vergleichsarm. Die Auswertung von insgesamt 18 Studien zeigte keinen Anhalt für eine erhöhte Inzidenz kardiovaskulärer Ereignisse unter einer SH-Therapie. Die verfügbaren Daten sind jedoch begrenzt und darüber hinaus herrscht ein Mangel an prospektiv geplanten, wirkstoffkontrollierten Studien mit hinreichender Teststärke für eine vergleichende Bewertung kardiovaskulärer Effekte. Da SH weiterhin als Zweitlinienmedikamente in Kombination mit Metformin und gegebenenfalls als Erstlinientherapie bei Typ-2-Diabetes empfohlen werden, sind konkrete kardiovaskuläre Sicherheitsdaten aus einer prospektiven, randomisierten, kontrollierten Studie dringend benötigt. Die CAROLINA^®-Studie ist bis heute die größte Studie für kardiovaskuläre Endpunkte, die einen SH und einen Dipeptidyl-Peptidase-4-Inhibitor (DPP-4) direkt vergleicht. Aufgrund ihres Designs und ihrer Teststärke kann CAROLINA^® im Direktvergleich einen detailierten Einblick in die kardiovaskuläre Sicherheit dieser Wirkstoffe geben.

Abstract

Sulphonylureas (SUs) are antidiabetic agents widely used in patients with Type 2 Diabetes Mellitus (T2DM). Observational retrospective studies have raised concerns regarding the cardiovascular (CV) safety of this class of drugs, and data from observational and registry studies are conflicting. To address the SU controversy, this review looked at longer-term RCTs, where SUs were compared in a head-to-head fashion with active comparators. An analysis of 18 studies did not find any increase in the incidence of CV events with SU therapy. However, the available data are limited and most importantly, there is a lack of prospective, adequately powered, formal head-to-head CV outcome trials. Since SUs are still being used as second-line therapy in combination with metformin and in some cases as first-line treatment of T2DM, there is a definite need for CV safety data from a prospective RCT. The CAROLINA^® study is currently the largest CV outcome study with a direct comparison of an SU and a dipeptidyl peptidase-4 inhibitor (DPP-4). Based on the study design and statistical power of CAROLINA^®, its results will provide a unique perspective regarding CV outcomes of these 2 commonly used agents.

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