NCT07701005·Not applicable·OBSERVATIONAL

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

Tirzepatide Semaglutide Glucagon Weight loss Completed

Status

Completed

Phase

Not applicable

Enrollment

154

Locations

Results

Not posted

Publications

Study summary

What the protocol is testing.

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.

Full 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

Treatment arms and agents.

DRUG

Semaglutide

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.

DRUG

Tirzepatide

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.

Timeline

From registration to results.

First posted
Jul 14, 2026
Study start
Jan 1, 2024
Primary completion
Mar 30, 2026
Study completion
Apr 15, 2026
Results posted
Not reported
Registry updated
Jul 15, 2026

Outcomes

What the study measures.

Primary outcomes

Change in Fibrosis-4 Index (FIB-4)

Time frame · 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)

Time frame · 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)

Time frame · 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

Time frame · 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.