Association of SGLT2 Inhibitors Therapy With Elastographic and Molecular Markers of Liver Injury in Type 2 Diabetes

NCT07269197 | Completed

• 1 other identifier: 2158-61-46-23-122
• Study Type: observational
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic dysfunction-associated steatotic liver disease (MASLD), a condition where fat builds up in the liver, is common in patients with type 2 diabetes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors may help improve liver health, but their effects on liver stiffness and fat are not yet well understood. This study aims to clarify these effects. Therefore, the aims of this study are:

1. 1.Measurement of liver stiffness and liver steatosis using novel ultrasound-based methods before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.
2. 2.Assessment of blood biomarkers that may indicate liver injury, increased fat accumulation, and cellular dysfunction before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.
3. 3.Evaluation of the relationship between biomarkers and ultrasound findings before the introduction of SGLT2 inhibitors and 6 months after the start of therapy.

Conditions

Non-Alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Keywords

elastography; UGAP; MASLD; SGLT2 inhibitor; fatty liver; empagliflozin; dapagliflozin; Diabetes mellitus type 2

Outcome Measures

Primary Outcomes (18)

• Change in liver fibrosis (kPa)

  Liver fibrosis is assessed using the two-dimensional shear wave elastography (2D-SWE)

  Baseline, after 6 months

• Change in liver steatosis (dB/cm/MHz)

  Liver steatosis is assessed using the ultrasound-guided attenuation parameter (UGAP).

  Baseline, after 6 months

• Change in glucose levels (mmol/L)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in HbA1c (%)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in HbA1c (mmol/mol)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in enzyme activity (U/L) of AST, ALT, GGT, ALP

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in Prothrombin Time ratio and change in activated Partial Thromboplastin Time ratio

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in Prothrombin Time-INR

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in fibrinogen activity (g/L)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in Thrombin Time (s) and change in activated Partial Thromboplastin Time (s)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in concentration (g/L) of albumins and total proteins

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in concentration (µmol/L) of total bilirubin and conjugated bilirubin

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in concentration (mmol/L) of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in in White Blood Cell (WBC) Count (x 10^9/L) and Platelet Count (x 10^9/L)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in Red Blood Cell (RBC) Count (x 10^12/L)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in Hemoglobin concentration (g/L)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in Hematocrit ratio (L/L)

  Assessment via biochemical analyses

  Baseline, after 6 months

• Change in concentration (ng/L) of SREBP-1, PPAR alpha, PPAR gamma and MTTP

  Assessment via ELISA

  Baseline, after 6 months

Secondary Outcomes (1)

• Questionnaire on lifestyle and dietary habits

  Baseline, after 6 months

Interventions

Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor DRUG

In patients with T2DM initiating therapy with a SGLT2 inhibitor, the effects on the liver have been assessed.

Also known as: Dapagliflozin, Empagliflozin, Jardiance, Forxiga

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with Type 2 Diabetes Mellitus who have been prescribed SGLT2 inhibitor for the first time in eastern Croatia region.

You may qualify if:

• Signed informed consent, information for the participants and questionnaire
• Patients that are 18 years of age or older
• Diagnosis of type 2 diabetes mellitus
• Patients being treated with an SGLT2 inhibitor for the first time
• Patients who have been on stable antihyperglycemic therapy for 90 days (3 months) before enrollment in the study

You may not qualify if:

• Patients taking drugs that are extremely hepatotoxic, i.e., require additional monitoring of liver function during therapy (e.g., chemotherapeutic agents, biological therapy)
• Patients taking drugs which cause drug-induced fatty liver disease (DIFLD): amiodarone, tamoxifen, methotrexate, 5-Fluorouracil, irinotecan, l-asparaginase, valproate, tetracycline, nucleoside reverse transcriptase inhibitors (NRTIs such as lamivudine, tenofovir, zidovudine etc.)
• Patients with liver cancer, hemochromatosis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), hepatitis C virus (HCV), hepatitis B virus (HBV), liver cirrhosis or autoimmune hepatitis.
• Patients who are alcohol addicted, i.e., consume more than two alcoholic beverages per day (for women) or more than three alcoholic beverages per day (for men)
• Mentally ill patients who are incapable of making their own independent decisions and have a legal custodian
• Pregnant women and nursing mothers
• Patients who are on insulin therapy

Sponsors & Collaborators

• Josip Juraj Strossmayer University of Osijek: lead

Study Sites (1)

Health Center Osijek-Baranja County

Osijek, 31000, Croatia

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Fatty Liver

Interventions

dapagliflozin; empagliflozin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Martina Smolić, MD, PhD

  Faculty of dental medicine and health Osijek, Josip Juraj Strossmayer University Osijek, 31000 Osijek, Croatia

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 8, 2025
• Study Start: March 22, 2024
• Primary Completion: October 10, 2025
• Study Completion: October 10, 2025
• Last Updated: December 8, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)