Hepatocentric approach to achieving compensation of diabetes mellitus in people with non-alcoholic steatohepatitis

Abstract

Background. Non-alcoholic steatohepatitis (NASH) in individuals with type 2 diabetes mellitus (T2DM) is considered a comorbid condition with an unfavorable prognosis and a signifi­cant economic burden on the global healthcare system. Despite patient-centered treatment goals and the coordinated efforts of a multidisciplinary team of physicians, a significant proportion of patients fail to achieve glycemic control, indicating the complex and multifactorial pathogenesis of T2DM. Achieving glycemic targets with a hepatocentric approach should be considered an alternative way to improve the treatment algorithm for patients with T2DM and NASH. The purpose of the study was to evaluate the hepatoprotective effect of dapagliflozin on achieving glycemic control in individuals with T2DM and NASH. Materials and methods. Sixty patients with T2DM and NASH were examined and divided into two groups based on antidiabetic therapy: group I (n = 30) received basic medi­cal therapy (BMT) which included metformin (2000 mg/day), alpha-lipoic acid (600 mg/day), and rosuvastatin (10 mg/day) in combination with insulin therapy; group II (n = 30) received BMT in combination with dapagliflozin at a daily dose of 10 mg. All patients underwent comprehensive laboratory tests, including calculations of non-invasive screening biomarkers (HEPAmet fibrosis score) and liver fibrosis severity (Fibrosis-4 index, FIB-4), as well as clinical and instrumental diagnostics using liver shear wave elastography (METAVIR, kPa). The study period lasted 12 weeks. Results. After 3 months of treatment, group I showed a tendency toward norma­lization of glycemic control parameters, while the level of glycated hemoglobin significantly decreased (∆ –22.92 %, p < 0.001) in group II. Throughout the study period, no episodes of hypoglycemia or adverse events were reported. The effectiveness of the additional administration of dapagliflozin supports the hepatocentric approach to achieving glycemic control with normalization of fibrosis markers (HEPAmet: AUC 0.828 (95% CI: 0.712–0.943, p < 0.001); FIB-4: AUC 0.765 (95% CI: 0.643–0.887, p < 0.001)) and a significant reduction of METAVIR scores (AUC 0.996 (95% CI: 0.986–1.005, p < 0.001)) according to liver shear wave elastography. Conclusions. The study results indicate that administration of dapagliflozin at a dose of 10 mg/day with BMT effectively impacts glycemic control and activates additional hepatoprotective mechanisms in patients with T2DM and NASH. A hepatocentric approach to the safe and effective management of T2DM in individuals with NASH is justified by the timely use of an updated treatment algorithm with an emphasis on sodium-glucose cotransporter 2 inhibitors.

Keywords

• type 2 diabetes mellitus
• non-alcoholic steatohepatitis
• sodium-glucose cotransporter 2 inhibitors
• dapagliflozin