BOSTON, MA—The SGLT2 inhibitor remogliflozin etabonate (Remo) might help improve fibrosis stage, according to a post-hoc analysis presented at The Liver Meeting® 2016.
“Remo improves insulin sensitivity, significantly lowers ALT and improves both FIB-4 and NAFLD-fibrosis scores,” reported lead study author William O. Wilkison, PhD, of BHV Pharma, Research Triangle Park, NC. “After 12 weeks of treatment with Remo, the improvement in FIB-4 scores are consistent with a predicted improvement in fibrosis stage.”
“Taken together, the preclinical and clinical data are highly suggestive that Remo may be a useful treatment for NASH,” he concluded.
Non-alcoholic steatohepatitis (NASH) is associated with insulin resistance and oxidative stress. Prior research has shown that Remo reduces HbA1 and improves glycemic control.
The authors of the new study sought to determine if that improved glycemic control is attributable to changes in insulin sensitivity, “and to what extent Remo may affect the non-invasive markers of fibrosis; FIB-4 and NAFLD Fibrosis scores.”
The analysis involved data for 336 adult patients (age 18–70 years) with type 2 diabetes and an HbA1c of >7.0–<9.5%, who had participated in a 12-week, double-blind, randomized, placebo-controlled trial. They were randomly assigned to placebo, pioglitazone (daily), or 1 of 5 Remo treatment doses (50, 100, 250, 500 or 1000mg, twice daily).
Labs were measured at baseline and every four weeks through Week 12. These included serum alanine aminotransferases (ALT), homeostatic model assessment (HOMA) for insulin sensitivity (HOMA-IS) and beta cell function (HOMA -BCF). Post-prandial assessments of glucose, insulin, and C-peptide were performed at Baseline and at Week 12 using a 2-hour oral glucose tolerance test (OGTT) in a subgroup of subjects. FIB-4 and NAFLD Fibrosis Scores were determined at Baseline and Week 12.”
“At Week 12, Remo improved both insulin sensitivity (6–39%) and beta cell function (23–43%) in a dose-dependent manner,” Dr Wilkison reported. “In subjects with elevated baseline ALT, Remo treatment resulted in a significant reduction (32–42%) in ALT at Week 12.”
Baseline FIB-4 scores suggested a range of fibrosis stages among patients, he noted.
“Remo, at all doses, had an effect of reducing the FIB-4 scores (5–17% reduction) compared to placebo,” Dr Wilkison said. “After 12 weeks of treatment with Remo, the FIB-4 scores were consistent with a predicted improvement in fibrosis stage. Similar results were noted for NAFLD Fibrosis scores.”
The findings indicate that Remo’s reversal of insulin resistance is associated with decreased ALT, improved FIB-4, and improved NAFLD Fibrosis scores, he concluded.