Orlistat

What the evidence says

Orlistat inhibits gastrointestinal lipases, reducing absorption of some dietary fat. Because it acts mainly in the gut, efficacy and adverse effects are tightly linked to what is eaten; it is prescribed with a nutritionally balanced, reduced-calorie diet.^[5]

Long-term meta-analysis found about 2.7 kg more weight loss than placebo at one year. A later network meta-analysis likewise ranked it below the most effective modern medicines but confirmed that more people achieve at least 5% weight loss than with placebo.^[2][3]

In XENDOS, 3,305 adults received lifestyle intervention plus orlistat or placebo for four years. Mean weight loss was 5.8 versus 3.0 kg, and diabetes incidence was lower overall, with the prevention signal concentrated in participants who had impaired glucose tolerance at baseline.^[1]

Across 33 randomized trials, orlistat also improved LDL cholesterol beyond weight change alone. These biomarker effects do not establish a mortality or cardiovascular-event benefit, and high attrition in long studies makes real-world persistence important.^[4][2]

Oily spotting, urgency, flatus with discharge, and fatty stools are common, especially after high-fat meals. The label also addresses fat-soluble vitamin supplementation, drug interactions, kidney-stone or oxalate-nephropathy risk, gallstones, and rare severe liver injury reports.^[5]