Non-Invasive Hepatic and Metabolic Index Changes After Incretin Therapy in Overweight/Obesity

NCT07701005 | Completed

• 1 other identifier: GLP-NIT
• Study Type: observational
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, retrospective observational cohort study evaluated early changes in non-invasive hepatic and metabolic indices (FIB-4, APRI, HSI, and the triglyceride-glucose \[TyG\] index) in adults with overweight or obesity who received once-weekly subcutaneous semaglutide or tirzepatide for metabolic risk reduction related to metabolic dysfunction-associated steatotic liver disease (MASLD). Baseline and follow-up (minimum 12 weeks) clinical, anthropometric, and laboratory data from 154 patients treated at a single tertiary-care center in Turkey were analyzed. The study assessed whether short-term incretin-based therapy was associated with changes in fibrosis-related indices (FIB-4, APRI) versus steatosis- and insulin resistance-related indices (HSI, TyG), and identified independent predictors of these changes using multivariable linear regression.

Conditions

Steatosis of Liver; Metabolic Liver Injury; Obesity; Overweight; Insulin Resistance

Keywords

MASLD; semaglutide; tirzepatide; FIB-4; Hepatic Steatosis Index; triglyceride-glucose index; incretin-based therapy; real-world evidence

Outcome Measures

Primary Outcomes (4)

• Change in Fibrosis-4 Index (FIB-4)

  FIB-4 = (Age × AST) / (Platelet count × √ALT), calculated at baseline and after ≥12 weeks of therapy.

  Baseline and follow-up (median 23.7 weeks; minimum 12 weeks)

• Change in AST-to-Platelet Ratio Index (APRI)

  APRI = (AST / 40 U/L ULN) / Platelet count × 100, calculated at baseline and after ≥12 weeks of therapy.

  Baseline and follow-up (median 23.7 weeks; minimum 12 weeks)

• Change in Hepatic Steatosis Index (HSI)

  HSI = 8 × (ALT/AST) + BMI + 2 (if type 2 diabetes) + 2 (if female), calculated at baseline and after ≥12 weeks of therapy.

  Baseline and follow-up (median 23.7 weeks; minimum 12 weeks)

• Change in Triglyceride-Glucose (TyG) Index

  yG = ln\[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL) / 2\], calculated at baseline and after ≥12 weeks of therapy.

  Baseline and follow-up (median 23.7 weeks; minimum 12 weeks)

Secondary Outcomes (7)

• Change in Liver Enzymes

  Baseline and follow-up (median 23.7 weeks)

• Change in Fasting Plasma Glucose

  Baseline and follow-up (median 23.7 weeks)

• Change in Lipid Profile

  Baseline and follow-up (median 23.7 weeks)

• Change in Body Weight

  Baseline and follow-up (median 23.7 weeks)

• Change in Glycated Hemoglobin (HbA1c)

  Baseline and follow-up (median 23.7 weeks)

Study Arms (2)

Semaglutide

Adults with overweight or obesity at increased metabolic risk for MASLD who received continuous once-weekly subcutaneous semaglutide for at least 12 weeks (n=81). Dose titration was at the treating physician's discretion.

Drug: Semaglutide

Tirzepatide

Adults with overweight or obesity at increased metabolic risk for MASLD who received continuous once-weekly subcutaneous tirzepatide for at least 12 weeks (n=73). Dose titration was at the treating physician's discretion.

Drug: Tirzepatide

Interventions

Semaglutide DRUG

Once-weekly subcutaneous GLP-1 receptor agonist administered for at least 12 weeks; dose individualized and titrated at the treating physician's discretion according to routine clinical practice and patient tolerability.

Also known as: Ozempic; Wegovy

Semaglutide

Tirzepatide DRUG

Once-weekly subcutaneous dual GIP/GLP-1 receptor agonist administered for at least 12 weeks; dose individualized and titrated at the treating physician's discretion according to routine clinical practice and patient tolerability.

Also known as: Mounjaro; Zepbound

Tirzepatide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with overweight or obesity at increased metabolic risk for MASLD, treated with subcutaneous semaglutide or tirzepatide for at least 12 weeks at a single tertiary-care internal medicine clinic in Turkey; both medications were self-funded (out-of-pocket), as they are not covered by the national health insurance system.

You may qualify if:

• Adults aged 18 years or older
• Overweight (BMI 25.0-29.9 kg/m²) or obesity (BMI ≥30.0 kg/m²)
• Considered at increased metabolic risk for MASLD (overweight/obesity plus ≥1 additional cardiometabolic risk factor)
• Continuous treatment with subcutaneous semaglutide or tirzepatide for at least 12 weeks

You may not qualify if:

• Significant alcohol consumption (\>30 g/day for men; \>20 g/day for women)
• Chronic liver disease of other etiology (viral hepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease)
• Prior bariatric surgery
• Initiation or dose modification of pioglitazone, SGLT-2 inhibitors, or high-dose vitamin E within 3 months before baseline
• Concurrent use of known hepatotoxic agents (e.g., amiodarone, methotrexate)
• Missing clinical, anthropometric, or laboratory data at baseline or follow-up

Sponsors & Collaborators

• Goztepe Prof Dr Suleyman Yalcın City Hospital: lead

Study Sites (1)

Facility: Istanbul Medeniyet University, Göztepe Prof. Dr. Süleyman Yalçın City Hospital

Istanbul, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Fatty Liver; Obesity; Overweight; Insulin Resistance

Interventions

semaglutide; Tirzepatide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Ozgur Bahadir, MD

  Istanbul Medeniyet University, Faculty of Medicine, Department of Gastroenterology

  PRINCIPAL INVESTIGATOR

• Ayse N Erbakan, MD,PhD

  Istanbul Medeniyet University, Faculty of Medicine, Department of Internal Medicine

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 14, 2026
• Study Start: January 1, 2024
• Primary Completion: March 30, 2026
• Study Completion: April 15, 2026
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)