Efficacy of Luseogliflozin Added to Semaglutide in Patients With Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes Mellitus: A Randomised, Open-Label Trial.
Teruki Miyake, Osamu Yoshida, Shinya Furukawa et al.
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In 30 seconds
This 52-week, open-label, randomised, parallel-group trial in Japan compared luseogliflozin plus semaglutide with semaglutide alone in adults with biopsy-proven MASH and type 2 diabetes. Sixty participants were randomised, and blinded pathologists assessed paired liver biopsies. In the full analysis set, combination therapy did not significantly improve the prespecified histological endpoints. MASH resolution without worsening fibrosis occurred in 34.9% versus 19.4%, respectively. Combination therapy improved several metabolic and liver-related measures; a NAS improvement was nominally significant only in the prespecified per-protocol analysis.
Key findings
- MASH resolution without worsening fibrosis occurred in 34.9% with combination therapy versus 19.4% with semaglutide alone.
- NAS improved by at least 1 point in 75.5% versus 55.6%; this was nominally significant in the per-protocol analysis.
- At least 1-stage fibrosis improvement occurred in 26.9% versus 13.9%, but prespecified histological endpoints were not significantly improved in the full analysis set.
- Combination therapy reduced body weight, glycated haemoglobin, aminotransferase levels and FibroScan-derived liver stiffness; no new safety concerns were identified.
Why it matters
The trial tests whether adding an SGLT2 inhibitor to a GLP-1 receptor agonist can improve liver histology in people with MASH and type 2 diabetes. Although the numerical differences favoured combination therapy, the primary full-analysis findings do not establish a significant histological benefit. Improvements in metabolic measures and liver stiffness are relevant outcomes, but should be distinguished from demonstrated histological improvement.
What to keep in mind
The trial was open-label and included 60 participants. The full analysis set did not show significant improvement in the prespecified histological endpoints; the nominal NAS finding was confined to the per-protocol analysis.