Insulin Resistance, Metabolic Liver Injury, Obesity, Overweight, Steatosis of Liver
Conditions
Keywords
MASLD, semaglutide, tirzepatide, FIB-4, Hepatic Steatosis Index, triglyceride-glucose index, incretin-based therapy, real-world evidence
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.
Detailed description
Adults aged 18 years or older with overweight or obesity who were considered at increased metabolic risk for MASLD and who received continuous subcutaneous semaglutide or tirzepatide for at least 12 weeks were retrospectively identified at the internal medicine clinic of a tertiary-care state hospital in Istanbul, Turkey. Patients with significant alcohol consumption, other chronic liver disease etiologies, prior bariatric surgery, recent initiation/dose change of MASLD-relevant medications, concurrent hepatotoxic agent use, or missing baseline/follow-up data were excluded. Baseline values were defined as the most recent measurements within 4 weeks before treatment initiation; follow-up values were the earliest measurements obtained after at least 12 continuous weeks of therapy. FIB-4, APRI, HSI, and TyG were calculated at both time points. Wilcoxon signed-rank tests compared baseline-to-follow-up changes. Kendall's tau assessed exploratory correlations among change scores; Spearman's rho assessed two prespecified correlations (percentage body-weight change vs. index changes; ΔHbA1c vs. index changes in the diabetic subgroup). Multivariable linear regression (enter method) identified independent predictors of ΔFIB-4, ΔAPRI, ΔHSI, and ΔTyG, adjusting for baseline index value, weight change, follow-up duration, baseline HbA1c, sex, and age. Agent choice (semaglutide vs. tirzepatide) and dose titration were at the discretion of the treating physician; patients receiving either agent were analyzed together as a drug class, without dose-based stratification, since the study's aim was to characterize the class-level early index response rather than compare individual agents.
Interventions
DRUGSemaglutide
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.
DRUGTirzepatide
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.
Sponsors
Goztepe Prof Dr Suleyman Yalcın City Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fibrosis-4 Index (FIB-4) | Baseline and follow-up (median 23.7 weeks; minimum 12 weeks) | FIB-4 = (Age × AST) / (Platelet count × √ALT), calculated at baseline and after ≥12 weeks of therapy. |
| Change in AST-to-Platelet Ratio Index (APRI) | Baseline and follow-up (median 23.7 weeks; minimum 12 weeks) | APRI = (AST / 40 U/L ULN) / Platelet count × 100, calculated at baseline and after ≥12 weeks of therapy. |
| Change in Hepatic Steatosis Index (HSI) | Baseline and follow-up (median 23.7 weeks; minimum 12 weeks) | HSI = 8 × (ALT/AST) + BMI + 2 (if type 2 diabetes) + 2 (if female), calculated at baseline and after ≥12 weeks of therapy. |
| Change in Triglyceride-Glucose (TyG) Index | Baseline and follow-up (median 23.7 weeks; minimum 12 weeks) | yG = ln\[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL) / 2\], calculated at baseline and after ≥12 weeks of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Liver Enzymes | Baseline and follow-up (median 23.7 weeks) | AST, ALT, and GGT levels (U/L). |
| Change in Fasting Plasma Glucose | Baseline and follow-up (median 23.7 weeks) | Fasting plasma glucose (mg/dL) |
| Change in Lipid Profile | Baseline and follow-up (median 23.7 weeks) | Total cholesterol, HDL-C, LDL-C, and triglycerides (mg/dL) |
| Change in Body Weight | Baseline and follow-up (median 23.7 weeks) | Body weight (kilograms). |
| Change in Glycated Hemoglobin (HbA1c) | Baseline and follow-up (median 23.7 weeks) | HbA1c (percentage of total hemoglobin, %). |
| Change in Body Mass Index (BMI) | Baseline and follow-up (median 23.7 weeks) | BMI (kg/m\^2), calculated from body weight and height. |
| Change in Waist-to-Height Ratio | Baseline and follow-up (median 23.7 weeks) | Waist-to-height ratio (unitless ratio: waist circumference \[cm\] / height \[cm\]). |
Countries
Turkey (Türkiye)
Contacts
PRINCIPAL_INVESTIGATOROzgur Bahadir, MD
Istanbul Medeniyet University, Faculty of Medicine, Department of Gastroenterology
STUDY_DIRECTORAyse N Erbakan, MD,PhD
Istanbul Medeniyet University, Faculty of Medicine, Department of Internal Medicine
Outcome results
None listed