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World J Hepatol. Oct 27, 2026; 18(10): 125505
Published online Oct 27, 2026. doi: 10.4254/wjh.125505
Changes in lipid biomarkers, liver stiffness and steatosis following sodium-glucose cotransporter two inhibitor therapy in type two diabetes
Farah Khaznadar, Kristina Bojanić, Omar Khaznadar, Ana Jurić, Marija Hefer, Kristina Kralik, Ana Petrović, Ana Hrženjak, Ana Lončar, Justinija Steiner, Martina Smolić, Robert Smolić
Farah Khaznadar, Kristina Bojanić, Marija Hefer, Ana Petrović, Martina Smolić, Robert Smolić, Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
Farah Khaznadar, Department of Pharmacology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
Kristina Bojanić, Department of Radiology, Health Center Osijek-Baranja County, Osijek 31000, Croatia
Omar Khaznadar, Department of Radiology, “Dr. Juraj Njavro” National Memorial Hospital Vukovar, Vukovar 32000, Croatia
Ana Jurić, Ana Hrženjak, Department of Internal Medicine, Našice General County Hospital, Našice 31500, Croatia
Kristina Kralik, Department of Medical Statistics and Medical Informatics, Faculty of medicine, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
Ana Lončar, Teaching Institute of Public Health for the Osijek Baranja County, Osijek 31000, Croatia
Justinija Steiner, Directorate, Health Center Osijek-Baranja County, Osijek 31000, Croatia
Author contributions: Smolić M, Bojanić K and Smolić R designed the research; Jurić A, Hrženjak A and Khaznadar F recruited patients, collected clinical samples, and acquired laboratory data; Kralik K performed the statistical analysis; Khaznadar F, Khaznadar O and Lončar A performed the literature search; Khaznadar F, Smolić M and Smolić R analyzed and interpreted the data; Khaznadar F wrote the original draft of the manuscript; Khaznadar F, Bojanić K, Khaznadar O, Smolić M and Lončar A reviewed and edited the manuscript; Smolić M, Smolić R, Bojanić K, Jurić A and Steiner J critically revised the manuscript for important intellectual content; Bojanić K, Khaznadar O, Hefer M, Petrović A and Khaznadar F performed imaging and experimental procedures; Smolić R acquired funding. All authors read and approved the final version of the manuscript.
AI contribution statement: No part of the manuscript was generated by AI. ChatGPT (OpenAI) was used solely for language polishing to improve readability. The authors take full responsibility for the scientific content, accuracy, integrity, and originality of the manuscript.
Supported by European Union-Next Generation EU through programme funding of the University of Osijek (UNIOS)-Institutional Project, No. 581-UNIOS-46.
Institutional review board statement: This study was approved by the Ethical Committee of the Faculty of Medicine, Josip Juraj Strossmayer University of Osijek (Approval No. 2158-61-46-23-122), the Health Center of Osijek-Baranja County (Approval No. 03-1311-1/23), the General County Hospital Našice (Approval No. 01-348/2-2024), and the Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek (Approval No. 2158/97-97-10-24-55).
Informed consent statement: All study participants provided written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare that they have no relevant conflicts of interest related to this article.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Martina Smolić, Full Professor, Research Dean, Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Crkvena 21, Osijek 31000, Croatia.
msmolic@fdmz.hr
Received: July 9, 2026
Revised: August 3, 2026
Accepted: September 10, 2026
Published online: October 27, 2026
Processing time: 104 Days and 18.1 Hours
BACKGROUND
Metabolic dysfunction-associated steatotic liver disease is a rapidly growing and often underrecognized public health challenge affecting most patients with type 2 diabetes mellitus (T2DM). Despite its high prevalence and substantial hepatic and cardiovascular burden, effective pharmacological treatment remains limited. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are promising therapeutic candidates because they lower glucose independently of insulin, improve insulin sensitivity, and provide renoprotective and cardioprotective benefits, with emerging evidence of potential hepatoprotective effects.
AIM
To assess changes in circulating lipogenesis biomarkers and liver imaging parameters following SGLT2i therapy.
METHODS
In this single-arm prospective observational study, 79 patients with T2DM initiating SGLT2i therapy were followed for six months. Peroxisome proliferator-activated receptor alpha (PPAR-α) and peroxisome proliferator-activated receptor gamma (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), and microsomal triglyceride transfer protein (MTTP) were assessed by enzyme-linked immunosorbent assay. Liver stiffness and steatosis were assessed using two-dimensional shear wave elastography (2D-SWE) and ultrasound-guided attenuation parameter (UGAP), with additional biochemical, anthropometric, and noninvasive fibrosis assessments.
RESULTS
Sixty-seven patients with T2DM completed six months of SGLT2i therapy. Treatment was associated with significant reductions in body mass index, waist circumference, fasting plasma glucose, and glycated hemoglobin (all P ≤ 0.04). Circulating PPAR-γ levels decreased from 895 ng/L to 565.4 ng/L, whereas MTTP concentrations increased from 198.4 ng/L to 428.9 ng/L (P < 0.001 for both). 2D-SWE-measured liver stiffness decreased from 6.2 kPa to 6.1 kPa (P < 0.001) and correlated positively with UGAP-assessed liver steatosis (ρ = 0.422, P < 0.001) and inversely with MTTP levels (ρ = -0.268, P = 0.03). Erythrocyte count, hemoglobin, hematocrit, and red blood cell indices changed significantly, while MTTP, SREBP-1c, and PPAR-α showed distinct associations with lipid and liver function markers (all P ≤ 0.04). Fibrosis and steatosis stages, along with non-alcoholic fatty liver disease fibrosis score and Fibrosis-4 index risk categories, remained largely stable, with a numerical increase in F0/F1 fibrosis, a decrease in F4, and balanced steatosis stages.
CONCLUSION
SGLT2i therapy was associated with modulation of circulating PPAR-γ and MTTP levels and a statistically significant but modest reduction in liver stiffness whose clinical relevance remains uncertain, while fibrosis and steatosis categories remained largely stable over 6 months. These findings support the metabolic effects of SGLT2i and warrant confirmation in larger controlled studies with longer follow-up and histological endpoints to determine whether these effects are accompanied by improvements in liver fibrosis and steatosis.
Core Tip: Metabolic dysfunction-associated steatotic liver disease lacks effective pharmacologic therapies and robust biomarkers for monitoring treatment response. In this prospective observational study, sodium-glucose cotransporter 2 inhibitors therapy was associated with modulation of selected circulating lipogenesis biomarkers and a modest reduction in liver stiffness of uncertain clinical relevance, whereas steatosis measures remained largely unchanged over 6 months.
