Eficácia da Luseogliflozina Adicionada ao Semaglutido em Pacientes com Esteatohepatite Associada à Disfunção Metabólica e Diabetes Mellitus Tipo 2: Ensaio Randomizado em Label Aberto

Resumo original em inglês

O que aconteceu

Type 2 diabetes drives the progression of metabolic dysfunction-associated steatohepatitis (MASH). We evaluated whether antidiabetic therapy, specifically adding sodium-glucose cotransporter 2 (SGLT2) inhibitor to a glucagon-like peptide-1 receptor agonist (GLP-1RA), improves liver histology in adults with biopsy-proven MASH and type 2 diabetes.

In this 52-week, open-label, randomised, parallel-group trial in Japan, adults with biopsy-confirmed MASH and type 2 diabetes received semaglutide plus luseogliflozin or semaglutide alone at antidiabetic doses. Paired liver biopsies at baseline and Week 52 were evaluated by blinded pathologists. Primary histological endpoints included resolution of MASH without worsening fibrosis, ≥ 1-point improvement in the non-alcoholic fatty liver disease (NAFLD) activity score without worsening fibrosis and ≥ 1-stage improvement in fibrosis without worsening MASH.

UMIN Clinical Trials Registry (UMIN-CTR): UMIN000045003; Japan Registry of Clinical Trials (jRCT): jRCTs061210009.

O que encontraram

Sixty participants were randomised (combination, n = 24; monotherapy, n = 36). At Week 52, all histological endpoints numerically favoured combination therapy. Resolution of MASH without worsening fibrosis occurred in 34.9% versus 19.4%, ≥ 1-point improvement in the NAFLD activity score (NAS) in 75.5% versus 55.6% and ≥ 1-stage fibrosis improvement in 26.9% versus 13.9%. In the pre-specified per-protocol analysis, ≥ 1-point improvement in the NAS was nominally significant. Combination therapy reduced body weight, glycated haemoglobin levels, aminotransferase levels and FibroScan-derived liver stiffness.

Por que isso importa

In the pre-specified full analysis set, combination therapy at antidiabetic doses did not significantly improve pre-specified histological endpoints compared with monotherapy. In the pre-specified per-protocol analysis, a nominal improvement in the NAS was observed. Combination therapy improved body weight, glycemic control, aminotransferase levels and liver stiffness, with no new safety concerns identified.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.