Semaglutid – ein neuer langwirksamer GLP-1-Rezeptor-Agonist mit nachgewiesener kardiovaskulärer Ereignisreduktion bei Typ-2-Diabetes

Zusammenfassung

Zur Therapie von Menschen mit Typ-2-Diabetes wurde mit Semaglutid ein neuer, lang wirksamer Glucagon-like-peptide-1-Rezeptor-Agonist (GLP-1-RA) für die einmal wöchentliche Gabe entwickelt. Das weltweite Phase-3-Studienprogramm umfasste mehr als 7000 Patienten, die in eine der randomisierten, kontrollierten Studien SUSTAIN 1 bis 6 eingeschlossen wurden. In SUSTAIN 1 bis 5 zeigten sich nach 30 bzw. 56 Wochen mittlere HbA_1c-Reduktionen zwischen 1,2 und 1,45 % (Semaglutid 0,5 mg) bzw. 1,5 und 1,8 % (Semaglutid 1,0 mg) mit signifikanten Vorteilen gegenüber Placebo, Sitagliptin 1 × täglich 100 mg, Exenatid-Depot-Injektionssuspension (nur 1,0 mg Semaglutid untersucht) und Insulin glargin 100 E/ml (Startdosis 10 E 1 × täglich). Das Körpergewicht verringerte sich unter Semaglutid im Mittel um 3,5 bis 4,3 kg (0,5 mg) und 4,5 bis 6,4 kg (1,0 mg). Die kardiovaskuläre Outcome-Studie SUSTAIN 6 ergab nach 2-jähriger Behandlung mit Semaglutid 0,5 mg oder 1,0 mg im Vergleich zu Placebo – jeweils im Rahmen des „Standard of Care“ – eine relative Risikoreduktion hinsichtlich des primären kombinierten kardiovaskulären Endpunkts um 26 % von absolut 8,9 % auf 6,6 % (p = 0,02 für die Überlegenheit). Außerdem zeigten sich unter Semaglutid im Vergleich zur Placebogruppe weniger Nephropathie-Ereignisse (3,8 % vs. 6,1 %; p = 0,005), aber mehr Retinopathie-Komplikationen (3,0 % vs. 1,8 %; p = 0,02), um 0,66 %-Punkte (0,5 mg) und 1,05 %-Punkte (1,0 mg) stärkere HbA_1c-Reduktionen nach 104 Wochen (jeweils p < 0,0001) und um 2,9 kg (0,5 mg) und 4,4 kg (1,0 mg) stärkere Gewichtsreduktionen (jeweils p < 0,0001). Wie bei anderen GLP-1-RA finden sich unter Semaglutid Reduktionen des systolischen Blutdrucks, Anstiege der Herzfrequenz, vermehrt gastrointestinale Nebenwirkungen und ein in Anbetracht der deutlichen HbA_1c-Reduktion relativ geringes Hypoglykämierisiko. Zusammenfassend liegen die Stärken von Semaglutid in einer ausgeprägt effektiven HbA_1c-Reduktion, der deutlichen Gewichtsreduktion und vorteilhaften kardiovaskulären Endpunktdaten.

Abstract

Semaglutide, a new long-acting Glucagon-like peptide-1 receptor agonist (GLP-1-RA) with once weekly dosing, was developed for the treatment of people with type 2 diabetes. The worldwide phase 3 trial programme included more than 7000 patients in the randomised, controlled SUSTAIN 1 to 6 studies. SUSTAIN 1 to 5 showed mean HbA_1c reductions between 1.2 and 1.45 % (semaglutide 0.5 mg) and 1.5 and 1.8 % (semaglutide 1.0 mg), respectively, after 30 or 56 weeks, with significant advantages over placebo, sitagliptin 100 mg once daily, exenatide prolonged-release suspension for injection (only semaglutide 1.0 mg was investigated) and insulin glargine 100 U/ml (starting dose 10 U once daily). The mean loss of body weight in patients on semaglutide 0.5 mg and 1.0 mg was 3.5 to 4.3 kg and 4.5 to 6.4 kg, respectively. The cardiovascular outcome study SUSTAIN 6 resulted in a relative risk reduction regarding the primary combined cardiovascular endpoint by 26 % of 8.9 % to 6.6 % (p = 0.02 for superiority) after a 2-year treatment with semaglutide 0.5 mg or 1.0 mg compared with placebo – each treatment in the context of the “standard of care”. Moreover, compared with the placebo group, patients on semaglutide showed less renal events (3.8 % vs. 6.1 %; p = 0.005), but more retinopathy complications (3.0 % vs. 1.8 %; p = 0.02), stronger HbA_1c reductions after 104 weeks by 0.66 % points and 1.05 % points for 0.5 and 1.0 mg, respectively (p < 0.0001 for both), and a stronger weight reduction by 2.9 kg (0.5 mg) and 4.4 kg (1.0 mg) (p < 0.0001 for both). As with other GLP-1-RAs, semaglutide is associated with reductions of systolic blood pressure, increased heart rate, increased gastrointestinal side effects and a relatively low risk of hypoglycemia considering the marked HbA_1c reduction. In summary, the strengths of semaglutide are a substantial HbA_1c reduction, the pronounced weight loss and beneficial cardiovascular endpoint data.

Schlüsselwörter

Typ-2-Diabetes - GLP-1-Rezeptor-Agonist - Semaglutid - kardiovaskulär

Key words

type 2 diabetes - GLP-1 receptor agonist - semaglutide - cardiovascular

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