Early Changes in Non-Invasive Hepatic and Metabolic Indices After Incretin-Based Therapy in Patients With Overweight or Obesity: Real-World Evidence From a Turkish Cohort
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Change in Fibrosis-4 Index (FIB-4)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Semaglutide (Drug)
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.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Change in Fibrosis-4 Index (FIB-4)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- Change in Lipid Profile(Baseline and follow-up (median 23.7 weeks))
- Change in Anthropometric Measures(Baseline and follow-up (median 23.7 weeks))
- Change in Glycemic Parameters(Baseline and follow-up (median 23.7 weeks))
- Change in Liver Enzymes(Baseline and follow-up (median 23.7 weeks))
- Change in Body Mass Index (BMI)(Baseline and follow-up (median 23.7 weeks))
- Change in Fasting Plasma Glucose(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))
- Change in Waist-to-Height Ratio(Baseline and follow-up (median 23.7 weeks))
研究者
Ayse N Erbakan
Associate Professor
Goztepe Prof Dr Suleyman Yalcın City Hospital