Toxicity and Safety Concerns in Orlistat Therapy for Obesity: A Critical Evaluation

Abstract

Orlistat is a selective inhibitor of gastric and pancreatic lipase indicated for the treatment of obesity. It is also known to significantly reduce risk of associated co-morbidities such as heart attack, type-2 diabetes mellitus, hypertension and stroke. Recent reports have raised concerns on the possible occurrence of serious adverse effects with prolonged use. Orlistat has been shown to inhibit carboxylesterase-2, a major detoxification enzyme, predisposing to severe liver, pancreatic and kidney damage. Orlistat alters the pharmacodynamic response of some drugs when co-administered leading to severe toxicity and reduced efficacy. Safety is a major concern considering the widespread use of this drug both as a prescription and over-the-counter medication. There is need for large-scale observation studies on orlistat use to generate appropriate data that will guide the regulatory agencies in taking relevant decision on continued use of orlistat as anti-obesity drug.