Baseline Characteristics of Patients With and Without Diabetes in STELLAR-3 and -4: Two Global Phase 3 Clinical Trials for Advanced Fibrosis Due to Nonalcoholic Steatohepatitis

Background:

Greater than 50% of patients with diabetes are estimated to have nonalcoholic steatohepatitis (NASH). Here we describe the baseline characteristics of patients with and without diabetes enrolled in 2 randomized, placebo-controlled, Phase 3 trials of selonsertib (SEL), an apoptosis signal-regulating kinase 1 (ASK1) inhibitor, studied for the treatment of advanced fibrosis in NASH.

Methods:

Patients recruited from > 400 sites in 24 countries underwent liver biopsy and were eligible based on presence of NASH and advanced fibrosis. Enrollment was stratified by diabetes status.

Results:

A total of 1679 patients (60% females; median age 60 y with diabetes and 58 y without diabetes) were enrolled. Patients with compensated cirrhosis had more diabetes (77% vs. 70% with bridging fibrosis). Patients with diabetes had higher values of hemoglobin A1C (HbA1c; 6.9% vs. 5.5%) and BMI (33.1 vs. 31.5 kg/m2) vs. without diabetes (all p < 0.05). Patients with diabetes had more severe liver fibrosis as estimated by liver stiffness by transient elastography (Fibroscan®; 16.8 vs. 14.0 kPa; all p < 0.001). SGLT-2 and GLP-1 medications were used in 20% of enrolled patients with diabetes. Long acting Insulins were used more in patients with compensated cirrhosis (27% vs. 21% in bridging fibrosis).

Conclusion:

Diabetes is an important risk factor for advanced fibrosis due to NASH; ˜70% of patients enrolled in these global Phase 3 trials have diabetes. Patients with diabetes appear to have more severe liver fibrosis.