Adiponectin in Patients With Metabolic Disorders

Adiponectin and Its Role in the Treatment of Patients With Metabolic Disorders

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.

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.