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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM); Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD)
• Intervention / Treatment: Drug: SGLT2 inhibitor; Drug: GLP-1 RA

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russia
  • Moscow, Russia, 129110
    • Moscow Regional Research and Clinical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Participants in the control group received no drug therapy for metabolic dysfunction-associated fatty liver disease (MAFLD). They continued their standard antidiabetic therapy as prescribed by their treating physician without any additional study interventions. All participants in the control group met the same inclusion/exclusion criteria as the intervention groups.
Experimental: SGLT2 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.	Drug: SGLT2 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.
Experimental: GLP-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.	Drug: GLP-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.
Experimental: SGLT2 inhibitor + GLP-1 RA; Participants received combination therapy with an SGLT2 inhibitor and a GLP-1 receptor agonist for 6 months. The specific drugs, doses, and regimens followed standard clinical practice as per the study protocol.	Drug: SGLT2 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.; Drug: GLP-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in serum HMW-adiponectin levels	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in liver steatosis (CAP)	Baseline, 6 months

Collaborators and Investigators

• Sponsor: Moscow Regional Research and Clinical Institute (MONIKI)
• Collaborators: Botkin Hospital; Sechenov University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): April 8, 2024

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Pharmacologic Actions; Chemical Actions and Uses; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: Adipo_0222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No