Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD), Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
Background. Metabolic dysfunction-associated fatty liver disease (MAFLD/MASLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with insulin resistance. Adiponectin, particularly its high-molecular-weight (HMW) form, is a promising biomarker of metabolic status. However, its role in predicting response to antidiabetic therapy remains unclear. Objective. To evaluate the association between circulating HMW-adiponectin levels and the clinical course of MAFLD in patients with T2DM receiving different treatment regimens: glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors), and their combination. Study Design. Open-label randomized controlled trial. Population. Adults aged 40-65 years with confirmed T2DM and MAFLD, body mass index 25-39.9 kg/m², with glycated hemoglobin exceeding the target by no more than 1%. Interventions. Patients were randomized into three intervention groups (n=30 each): SGLT2 inhibitor monotherapy, GLP-1 RA monotherapy, or combination therapy. A control group (n=40) received no drug therapy for MAFLD. Outcome Measures. Primary outcome: change in serum HMW-adiponectin levels from baseline to 6 months. Secondary outcome: change in liver steatosis measured by Controlled Attenuation Parameter (CAP). Timeframe. Follow-up duration: 6 months. Conclusion. This study will determine whether baseline HMW-adiponectin levels predict the reduction in liver steatosis in response to SGLT2 inhibitors, GLP-1 RAs, or their combination in patients with T2DM and MAFLD/MASLD.
Interventions
DRUGSGLT2 inhibitor
SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors) are antidiabetic drugs that lower blood glucose by promoting glucosuria, leading to caloric loss and weight reduction. In this study, patients received standard clinical doses (e.g., dapagliflozin 5-10 mg once daily or empagliflozin 10-25 mg once daily) for 6 months.
DRUGGLP-1 RA
GLP-1 receptor agonists (glucagon-like peptide-1 receptor agonists) are antidiabetic drugs that enhance glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying, and reduce appetite. In this study, patients received standard clinical doses (e.g., liraglutide 1.2-1.8 mg once daily or semaglutide 0.5-1.0 mg once weekly) for 6 months.
Sponsors
Moscow Regional Research and Clinical Institute (MONIKI)
Botkin Hospital
Sechenov University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent of the patient to participate in the study * Glycated hemoglobin level exceeding the target by no more than 1%. * Age 40 to 65 years inclusive * Verified diagnosis of MAFLD, according to the criteria of EASL 2020, * Confirmed diagnosis of type 2 diabetes mellitus * Body mass index (BMI) 25-39.9 kg/m2 * Refusal to take any dietary supplements Non-inclusion criteria: * Chronic alcohol abuse (alcoholic fatty liver disease) * Insulin-dependent diabetes * Use of hepatoprotective agents * High risk of atherosclerotic cardiovascular disease (age \> 55 years with coronary, carotid, or lower extremity artery stenosis, or left ventricular hypertrophy) * Chronic kidney disease * Chronic heart failure
Exclusion criteria
* Patient withdrawal of consent * Pregnancy (if applicable) * Decompensation of diabetes during therapy * Development of adverse events associated with therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in serum HMW-adiponectin levels | Baseline and 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in liver steatosis (CAP) | Baseline, 6 months |
Countries
Russia
Outcome results
None listed