Non-Alcoholic Fatty Liver DiseaseNCT07269197
Association of SGLT2 Inhibitors Therapy With Elastographic and Molecular Markers of Liver Injury in Type 2 Diabetes
An observational study of Non-Alcoholic Fatty Liver Disease and Diabetes Mellitus, Type 2, run by Josip Juraj Strossmayer University of Osijek at 1 site in Croatia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2
- What is being tested?
- Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor
- How many people
- 67 participants
- Where
- 1 siteCroatia
- Study dates
- 22 Mar 2024to 10 Oct 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with Type 2 Diabetes Mellitus who have been prescribed SGLT2 inhibitor for the first time in eastern Croatia region.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Association of Sodium-Glucose Cotransporter 2 Inhibitors Therapy With Elastographic and Molecular Markers of Liver Injury in Patients With Type 2 Diabetes Mellitus
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:
- Measurement of liver stiffness and liver steatosis using novel ultrasound-based methods before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.
- 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.
- Evaluation of the relationship between biomarkers and ultrasound findings before the introduction of SGLT2 inhibitors and 6 months after the start of therapy.
Read the 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.
- Being tested
- Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor
- Keywords
- elastography, UGAP, MASLD, SGLT2 inhibitor, fatty liver, empagliflozin, dapagliflozin, Diabetes mellitus type 2
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Glucose Co-transporter 2 (SGLT2) InhibitorDrug
Also called Dapagliflozin, Empagliflozin, Jardiance, Forxiga
In patients with T2DM initiating therapy with a SGLT2 inhibitor, the effects on the liver have been assessed.
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in liver fibrosis (kPa)
Liver fibrosis is assessed using the two-dimensional shear wave elastography (2D-SWE)
Measured: Baseline, after 6 months
Change in liver steatosis (dB/cm/MHz)
Liver steatosis is assessed using the ultrasound-guided attenuation parameter (UGAP).
Measured: Baseline, after 6 months
Change in glucose levels (mmol/L)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in HbA1c (%)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in HbA1c (mmol/mol)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in enzyme activity (U/L) of AST, ALT, GGT, ALP
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in Prothrombin Time ratio and change in activated Partial Thromboplastin Time ratio
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in Prothrombin Time-INR
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in fibrinogen activity (g/L)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in Thrombin Time (s) and change in activated Partial Thromboplastin Time (s)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in concentration (g/L) of albumins and total proteins
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in concentration (µmol/L) of total bilirubin and conjugated bilirubin
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in concentration (mmol/L) of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
Assessment via biochemical analyses
Measured: 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
Measured: Baseline, after 6 months
Change in Red Blood Cell (RBC) Count (x 10^12/L)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in Hemoglobin concentration (g/L)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in Hematocrit ratio (L/L)
Assessment via biochemical analyses
Measured: Baseline, after 6 months
Change in concentration (ng/L) of SREBP-1, PPAR alpha, PPAR gamma and MTTP
Assessment via ELISA
Measured: Baseline, after 6 months
Secondary outcomes (1)
Questionnaire on lifestyle and dietary habits
Responses from a study-specific questionnaire including investigator-measured variables (weight [kg], height [cm], BMI [kg/m^2], blood pressure [mmHg], waist circumference [cm]) and patient-reported items (education, medical conditions, medications and side effects, recent antibiotic use, pregnancy/breastfeeding, supplement use). Lifestyle behaviors include alcohol intake, tobacco use, and physical activity (1 = never to 4 = very often). Dietary habits include frequency of consuming vegetables, fruits, meat, dairy, and high-calorie/junk foods (1 = almost never to 4 = very often). The questionnaire does not generate a composite or total score. Each variable will be analyzed individually as categorical, continuous, or ordinal data, depending on the question type.
Measured: Baseline, after 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2025
- Study start22 Mar 2024
- Primary completion10 Oct 2025
- Study completion10 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Josip Juraj Strossmayer University of Osijek
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Farah Khaznadar, Josip Juraj Strossmayer University of Osijek
- Investigators
- Martina Smolić, MD, PhD, Study director, Faculty of dental medicine and health Osijek, Josip Juraj Strossmayer University Osijek, 31000 Osijek, Croatia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07269197
- Sponsor's protocol ID
- 2158-61-46-23-122
- Status last verified
- Nov 2025
- First submitted
- 17 Nov 2025
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Association of Sodium-Glucose Cotransporter 2 Inhibitors Therapy With Elastographic and Molecular Markers of Liver Injury in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT07269197
- Acronym / sponsor ID
- 2158-61-46-23-122
- Keywords
- elastography, UGAP, MASLD, SGLT2 inhibitor, fatty liver, empagliflozin, dapagliflozin, Diabetes mellitus type 2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Josip Juraj Strossmayer University of OsijekUniversity, hospital or other
- Study start
- 22 Mar 2024 (actual)
- Primary completion
- 10 Oct 2025 (actual)
- Study completion
- 10 Oct 2025 (actual)
- First posted
- 8 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Measurement of liver stiffness and liver steatosis using novel ultrasound-based methods before initiating SGLT2 inhibitor therapy and 6 months after starting therapy.
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Type 2 Diabetes Mellitus who have been prescribed SGLT2 inhibitor for the first time in eastern Croatia region.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium Glucose Co-transporter 2 (SGLT2) InhibitorAlso: Dapagliflozin, Empagliflozin, Jardiance, ForxigaIn patients with T2DM initiating therapy with a SGLT2 inhibitor, the effects on the liver have been assessed. | Drug | – |
Primary outcome
Change in liver fibrosis (kPa)
Time frame: Baseline, after 6 months
Liver fibrosis is assessed using the two-dimensional shear wave elastography (2D-SWE)
Change in liver steatosis (dB/cm/MHz)
Time frame: Baseline, after 6 months
Liver steatosis is assessed using the ultrasound-guided attenuation parameter (UGAP).
Change in glucose levels (mmol/L)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in HbA1c (%)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in HbA1c (mmol/mol)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in enzyme activity (U/L) of AST, ALT, GGT, ALP
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in Prothrombin Time ratio and change in activated Partial Thromboplastin Time ratio
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in Prothrombin Time-INR
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in fibrinogen activity (g/L)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in Thrombin Time (s) and change in activated Partial Thromboplastin Time (s)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (g/L) of albumins and total proteins
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (µmol/L) of total bilirubin and conjugated bilirubin
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (mmol/L) of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in in White Blood Cell (WBC) Count (x 10^9/L) and Platelet Count (x 10^9/L)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in Red Blood Cell (RBC) Count (x 10^12/L)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in Hemoglobin concentration (g/L)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in Hematocrit ratio (L/L)
Time frame: Baseline, after 6 months
Assessment via biochemical analyses
Change in concentration (ng/L) of SREBP-1, PPAR alpha, PPAR gamma and MTTP
Time frame: Baseline, after 6 months
Assessment via ELISA
1 secondary outcome
Questionnaire on lifestyle and dietary habits
Time frame: Baseline, after 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martina Smolić, MD, PhD study director
Faculty of dental medicine and health Osijek, Josip Juraj Strossmayer University Osijek, 31000 Osijek, Croatia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-Alcoholic Fatty Liver Disease and Diabetes Mellitus, Type 2, run by Josip Juraj Strossmayer University of Osijek at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in liver fibrosis (kPa) (time frame: Baseline, after 6 months). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.