Short answer: Xenical (orlistat) is a 120 mg capsule taken with each main meal that contains fat; it blocks some fat from being absorbed. Wegovy (semaglutide) is a GLP-1 drug taken as a weekly injection or daily tablet.12 They were tested in separate trials, not head to head: Xenical averaged about 3% more weight loss than placebo at 1 year; Wegovy 2.4 mg averaged −14.9% vs −2.4% at 68 weeks.
| Xenical (orlistat) | Wegovy (semaglutide) | |
|---|---|---|
| How it works | Blocks gut lipase enzymes, so some dietary fat passes unabsorbed; very little reaches the blood1 | GLP-1 receptor agonist2 |
| Form and dose | 120 mg capsule three times a day with each main meal containing fat (during or up to 1 hour after)1 | Injection: 0.25 mg weekly, stepped up every 4 weeks; usual dose 2.4 mg. Tablet: 1.5 mg daily, stepped up every 30 days to 25 mg2 |
| Approved for | Weight loss and maintenance with a reduced-calorie diet; lowering weight regain; BMI 30 or more, or 27 or more with risk factors1 | Weight reduction (ages 12 and up for the injection); lowering heart attack, stroke and cardiovascular death in adults with heart disease; MASH with liver fibrosis2 |
| 1-year label trials | Pooled 5 trials: −13.4 lb vs −5.8 lb on placebo; about 3% difference1 | Study 2, 68 weeks: −14.9% vs −2.4% on placebo2 |
| Lost at least 5% | 35.5% to 54.8% vs 16.0% to 27.4% on placebo across 5 trials1 | 83.5% vs 31.1% on placebo2 |
| Longest trial | XENDOS, 4 years: 45% vs 28% lost at least 5%; mean difference 2.5%1 | 68 weeks in the weight trials2 |
| Most common side effects | Year 1: oily spotting 26.6% vs 1.3%; gas with discharge 23.9% vs 1.4%; urgent bowel movements 22.1% vs 6.7%1 | Nausea 44% vs 16% on placebo2 |
| Vitamins | Take a multivitamin with fat-soluble vitamins at least 2 hours apart from Xenical1 | No vitamin rule in the label2 |
| Boxed warning | None | Risk of thyroid C-cell tumors2 |
No. Xenical's 1-year numbers come from pooled trials that report pounds lost and the share reaching 5% and 10%, and from the 4-year XENDOS study, where only 52% on Xenical and 34% on placebo finished.1 Wegovy's Study 2 ran 68 weeks in 1,961 adults and reports percent change in body weight.2 These numbers come from separate placebo-controlled trials with different people, lengths and methods, so they are not a head-to-head comparison.
That is a decision for you and your prescriber, based on your health, other medicines, whether you prefer a capsule with meals or a weekly shot, and coverage. For other options, see Wegovy vs Contrave: what do the labels show? and Lomaira vs Qsymia: what is the difference?.
More detail: Xenical side effects, Wegovy side effects, the Xenical and Wegovy dosing schedules, a missed Wegovy dose and how to store Wegovy.