# Long‐Term Effects of Orlistat on Lipid Metabolism and Anthropometric Indices: A Meta‐Analysis of Clinical Trials

## TL;DR

Orlistat lowers BMI but may reduce HDL cholesterol, with uncertain effects on waist circumference and triglycerides.

## Contribution

A meta-analysis of clinical trials revealing orlistat's long-term effects on lipid metabolism and body measurements.

## Key findings

- Orlistat significantly reduces BMI but lowers HDL cholesterol.
- Triglyceride and waist circumference reductions are uncertain due to conflicting results.
- Prolonged use may lead to a modest decline in triglycerides over time.

## Abstract

Orlistat is a potent lipase inhibitor utilized as a preventive agent for obesity and fat absorption control. Existing literature presents conflicting findings regarding its impact on lipid parameters.

This systematic review followed the PRISMA guidelines and was registered in PROSPERO (ID: CRD42024550889). A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Register of Controlled Trials was conducted for studies published before January 19, 2025. Eligible studies included randomized controlled trials (RCTs) evaluating orlistat in adults (≥ 18 years) with dyslipidemia. Furthermore, the Grading of Recommendations, Assessment, Development, and Evaluations assessment tool was employed to analyze the certainty of evidence or each outcome.

A total number of 1369 participants, with 682 in treatment and 687 in control categories, were included in our study. Orlistat reduced body mass index (BMI) (SMD [95% CI]: −0.30 [‐0.58, −0.03], p value (heterogeneity) = 0.026), and also it was associated with a decrease in high‐density lipoprotein cholesterol (SMD (95% CI): −0.31 [‐0.48, −0.13], p value (heterogeneity) = 0.436). Changes in waist circumference (WC) and triglycerides (TGs) did not reach statistical significance in the primary analysis (WC: SMD [95% CI] −0.1562 [‐0.3138; 0.0015], I
2 = 0.0%, p‐value (heterogeneity) = 0.7572; TG: SMD [95% CI] −0.1668 [‐0.7979; 0.4642], I
2 = 97.7% p value (heterogeneity) < 0.0001); however, after publication‐bias adjustment using the trim‐and‐fill sensitivity analysis, meaningful reductions were discovered for WC (SMD (%95CI): −0.1712 [‐0.3248; −0.0176], I
2 = 0.0%, p value (heterogeneity) = 0.7696) and TG (SMD (%95CI): −0.8900 [‐1.6619; −0.1181], I
2 = 97.9%, p value (heterogeneity) < 0.0001). The secondary analysis demonstrated that follow‐up duration accounted for 30% of TG heterogeneity, suggesting a small but significant decline in orlistat’s TG‐lowering effect over time (slope: −0.1239; 95% CI: −0.2355, −0.0123; p value = 0.0295). No significant changes were observed in other parameters of the study. Besides, gastrointestinal issues were the most frequently reported adverse events among the studies.

Our findings suggest that orlistat meaningfully reduces BMI but is associated with decreased HDL‐C, which may be undesirable given HDL‐C’s protective role in cardiovascular health. Evidence for reductions in TG and WC is uncertain: the primary meta‐analysis showed no statistically significant effects, whereas trim‐and‐fill sensitivity analysis suggested potential reductions. No significant short‐term impact on TG was observed, though a modest reduction may emerge with prolonged use.