Keywords
insulin resistance
non-alcoholic steatohepatitis
fetuin-A
sodium-glucose cotransporter 2 inhibitors
dapagliflozin
empagliflozin
How to Cite
Abstract
Non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes (T2D) remains one of the leading medical and social problems of a modern time due to the increased risk of developing steatogenic liver cirrhosis and macrovascular complications. Metabolic dysfunction-associated steatotic liver disease worsens the course of T2D and forms a continuum of pathogenetic disorders. Modern therapeutic strategies require the introduction of biomarkers that reflect the effectiveness of treatment and help to evaluate alternative mechanisms of pharmacological effect of hypoglycemic drugs. The aim is to determine the level of fetuin-A as a marker of hepatoprotective efficacy of a 12-week course of therapy with sodium-dependent glucose cotransporter 2 inhibitors (SGLT2і) in individuals with T2D and NASH. Material and methods. The study included 48
patients with T2D and NASH, who were divided into four groups according to their therapeutic strategy: Group I (n=12) received basic drug therapy (BDT): metformin 2000 mg/day, α-lipoic acid 600 mg/day, rosuvastatin 10 mg/day; Group II (n=12) – BDT in combination with insulin therapy; Group III (n=12) received BDT in combination with 10 mg/day dapagliflozin (DAPA); Group IV (n=12) received BDT in combination with 10-25 mg/day empagliflozin (EMPA). The study lasted 12 weeks. Results. After 12 weeks of treatment, the most pronounced hepatoprotective effect was observed in patients of groups III and IV who received gliflozins as part of BDT. Mediation analysis showed that when insulin therapy was used, the reduction in fetuin-A levels was almost entirely due to improved glycemic control through glycated hemoglobin (HbA1c) (ACME=-0.10; 95% CI -0.22; -0.01), while the direct hepatocentric effect was minimal. SGLT2і in groups III and IV of the study enhanced the reduction in fetuin-A
content, both indirectly through HbA1c (ACME = -0.23 and -0.20) and directly (ADE -0.32 and -0.30; both p<0.01), with about 40% of the effect explained by the glycemic mechanism and the rest by direct hepatoprotective properties. Conclusions. Assessment of fetuin-A level as an early biomarker of the hepatoprotective effect of gliflozins allows to improve personalized NASH therapy in patients with T2D. Timely prescription of SGLT2і (DAPA 10 mg/day or EMPA 10-25 mg/day) as part of BDT is an effective, pathogenetically justified treatment algorithm with pronounced epatoprotective properties.
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