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

NCT ID: NCT07269197

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 67 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-03-22
• Study Completion Date: 2025-10-10

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. Measurement of liver stiffness and liver steatosis using novel ultrasound-based methods before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.

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. Evaluation of the relationship between biomarkers and ultrasound findings before the introduction of SGLT2 inhibitors and 6 months after the start of therapy.

Detailed Description

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among patients with type 2 diabetes mellitus (T2DM), yet targeted therapeutic strategies remain limited. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated favorable metabolic and potential hepatoprotective effects, however, their impact on liver stiffness and steatosis has not been fully characterized.

This study was conducted to assess the effects of SGLT2 inhibitor therapy on non-invasive elastographic parameters and markers of liver injury in patients with T2DM. Liver stiffness was assessed using two-dimensional shear wave elastography (2D-SWE) and liver steatosis using ultrasound-guided attenuation parameter (UGAP), at baseline and after 6 months of treatment.

Comprehensive biochemical analysis was performed, including glucose, HbA1c, hematologic parameters, and standard liver function markers (AST, ALT, GGT, ALP, coagulation profile, albumin, total proteins, total and conjugated bilirubin, and lipid profile). Additionally, serum concentrations of key regulators of lipogenesis: Sterol Regulatory Element-Binding Protein 1 (SREBP1), Peroxisome Proliferator-Activated Receptor alpha (PPAR-α), Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ), and Microsomal Triglyceride Transfer Protein (MTTP), were assessed at both time points.

The analysis aims to determine whether SGLT2 inhibitor therapy is associated with measurable improvements in liver stiffness, steatosis, and molecular markers of hepatic metabolic dysfunction, as well as to explore correlations between elastographic findings and circulating biomarkers. The results are expected to inform future research on the utility of these markers for diagnosing and monitoring MASLD and to support the potential expansion of therapeutic indications for SGLT2 inhibitors.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

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

Intervention Type: DRUG

Other Intervention Names

Dapagliflozin; Empagliflozin; Jardiance; Forxiga

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent, information for the participants and questionnaire

2. Patients that are 18 years of age or older

3. Diagnosis of type 2 diabetes mellitus

4. Patients being treated with an SGLT2 inhibitor for the first time

5. Patients who have been on stable antihyperglycemic therapy for 90 days (3 months) before enrollment in the study

Exclusion Criteria

1. Patients taking drugs that are extremely hepatotoxic, i.e., require additional monitoring of liver function during therapy (e.g., chemotherapeutic agents, biological therapy)

2. 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.)

3. 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.

4. 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)

5. Mentally ill patients who are incapable of making their own independent decisions and have a legal custodian

6. Pregnant women and nursing mothers

7. Patients who are on insulin therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Josip Juraj Strossmayer University of Osijek

OTHER

Sponsor Role: lead

Responsible Party

Farah Khaznadar

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martina Smolić, MD, PhD

Role: STUDY_DIRECTOR

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

Locations

Health Center Osijek-Baranja County

Osijek, , Croatia

Countries

Croatia

Other Identifiers

2158-61-46-23-122

Identifier Type: -

Identifier Source: org_study_id