Diabetes Mellitus, Type 2, Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
elastography, UGAP, MASLD, SGLT2 inhibitor, fatty liver, empagliflozin, dapagliflozin, Diabetes mellitus type 2
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.
Interventions
In patients with T2DM initiating therapy with a SGLT2 inhibitor, the effects on the liver have been assessed.
Sponsors
Josip Juraj Strossmayer University of Osijek
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Red Blood Cell (RBC) Count (x 10^12/L) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in Hematocrit ratio (L/L) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in concentration (ng/L) of SREBP-1, PPAR alpha, PPAR gamma and MTTP | Baseline, after 6 months | Assessment via ELISA |
| Change in Hemoglobin concentration (g/L) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in liver fibrosis (kPa) | Baseline, after 6 months | Liver fibrosis is assessed using the two-dimensional shear wave elastography (2D-SWE) |
| Change in liver steatosis (dB/cm/MHz) | Baseline, after 6 months | Liver steatosis is assessed using the ultrasound-guided attenuation parameter (UGAP). |
| Change in glucose levels (mmol/L) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in HbA1c (%) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in HbA1c (mmol/mol) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in enzyme activity (U/L) of AST, ALT, GGT, ALP | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in Prothrombin Time ratio and change in activated Partial Thromboplastin Time ratio | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in Prothrombin Time-INR | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in fibrinogen activity (g/L) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in Thrombin Time (s) and change in activated Partial Thromboplastin Time (s) | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in concentration (g/L) of albumins and total proteins | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in concentration (µmol/L) of total bilirubin and conjugated bilirubin | Baseline, after 6 months | Assessment via biochemical analyses |
| Change in concentration (mmol/L) of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides | 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) | Baseline, after 6 months | Assessment via biochemical analyses |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Questionnaire on lifestyle and dietary habits | Baseline, after 6 months | 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. |
Countries
Croatia
Outcome results
None listed