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Zepbound vs Xenical

Last reviewed: September 2026Based on 2 clinical trials

Zepbound (tirzepatide, weekly injection) and Xenical (orlistat, capsule, three times daily with meals) are both approved for weight loss in the United States. No head-to-head trial has compared these two drugs. The figures below come from separate trials, each with its own participants, length and comparison group.

At a glance

Zepbound and Xenical compared on form, trial results, cost and reported side effects
AttributeZepboundXenical
FormWeekly injection3x daily with meals
How oftenOnce-weekly injectionThree capsules daily, taken with each fat-containing meal
Weight loss in trialsUp to 20.9% — SURMOUNT-1 (72 weeks)Up to 8.5% — Sjostrom 1-year RCT (52 weeks)
FDA approved20231999
Made byEli LillyRoche (Xenical) / GSK (Alli OTC)
How it worksA single molecule that activates two hunger-regulating signals in the brain — GIP and GLP-1 (both natural hormones released after eating).Blocks pancreatic lipase enzymes in the small intestine, preventing approximately 30% of dietary fat from being broken down and absorbed.
Monthly cost, self-pay$299–$449/mowith the manufacturer savings programme; list price ~$1,086$40–$400/moover-the-counter strength; prescription runs to $400
Most reported reactionNausea 31% (SURMOUNT-1)Oily/fatty stools (steatorrhoea) 27% (XENDOS)
Every figure in this table is read from the same trial and label records used everywhere else on this site.

Weight loss in each drug's main trial

No head-to-head trial has compared these two drugs.

Zepbound(tirzepatide)20.9%

SURMOUNT-1 (72 weeks)

Xenical(orlistat)8.5%

Sjostrom 1-year RCT (52 weeks)

In clinical trials, participants taking tirzepatide lost on average up to 20.9% of their starting body weight, and participants taking orlistat lost on average up to 8.5%. Those numbers come from two different studies: SURMOUNT-1 enrolled 2,539 adults with obesity or overweight with comorbidities, no type 2 diabetes over 72 weeks against placebo, while Sjostrom 1-year RCT enrolled 743 adults with obesity over 1 year (52 weeks) against placebo. Who took part, how long each trial ran and what each drug was measured against all move the percentage, so the two figures are not a measured difference between the drugs.

Monthly cost, self-pay

The bar spans the range in each drug's price record — lowest listed price to highest.

Zepbound$299–$449/mo

with the manufacturer savings programme; list price ~$1,086

Self-pay via LillyDirect from $299/month (2.5 mg) to $449/month (7.5 mg and above), per zepbound.lilly.com on 10 September 2026; list price without the savings programme ~$1,086/month; $25/month copay card for eligible commercial insurance.

Xenical$40–$400/mo

over-the-counter strength; prescription runs to $400

Prescription Xenical ~$200–$400/month; over-the-counter Alli (60mg) ~$40–$60/month.

Self-pay prices are what the manufacturer or the pharmacy lists, not what most people end up paying. Zepbound: $299–$449/month. Xenical: $40–$400/month. Insurance, dose and pharmacy all change both figures.

Side effects reported in the trials

SURMOUNT-1 and XENDOS did not report the same reactions, so there is no shared row to line up. Each drug's own reported rates are listed below.

Zepbound
  • Nausea31%
  • Diarrhoea23%
  • Vomiting18%
  • Constipation12%
  • Decreased appetite19%

From SURMOUNT-1

Xenical
  • Oily/fatty stools (steatorrhoea)27%
  • Faecal urgency22%
  • Oily spotting on underwear27%
  • Faecal incontinence8%
  • Abdominal pain/discomfort14%

From XENDOS

A rate is the share of trial participants who reported that reaction, not a prediction for any one person.

How they differ in practice

How you take it

  • Zepbound — Once-weekly subcutaneous injection (2.5, 5, 7.5, 10, 12.5, 15 mg)
  • Xenical — Oral capsule 120 mg, three times daily with meals (prescription). Also available OTC as Alli at 60 mg.

How soon it acts

  • Zepbound — Noticeable appetite reduction typically within 4–8 weeks; significant weight loss by 12–16 weeks
  • Xenical — Weight effects begin from the first week (related to calorie malabsorption), but significant loss takes 8–12 weeks

Heart and metabolic findings

  • Zepbound — Improvements in systolic/diastolic blood pressure, triglycerides, LDL, and HbA1c across SURMOUNT trials.
  • Xenical — In the 4-year XENDOS trial, orlistat reduced progression from prediabetes to type 2 diabetes by 37% compared to placebo plus lifestyle changes.

As stated in each drug’s trial record — not a claim about which drug protects the heart more.

Other findings recorded

  • Zepbound — Reduced progression to type 2 diabetes; improved sleep apnoea (SURMOUNT-OSA trial)
  • Xenical — 37% reduction in progression to type 2 diabetes (XENDOS, 4 years); only approved obesity drug with a 4-year safety dataset

If you stop taking it

  • Zepbound — In SURMOUNT-4, participants who switched to placebo regained an average of 14.0% body weight over 52 weeks.
  • Xenical — Weight is typically regained after stopping.

Common questions

Written and maintained by one person · Built with agentic AI tools · Every number checked against the cited trial · Not medical advice

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Next step most people take

Compare all optionsEvery approved drug side by side, plus the other head-to-head pagesZepbound in fullZepbound & Mounjaro — results, side effects, cost and how it is takenXenical in fullXenical & Alli — results, side effects, cost and how it is takenTake the option finder quizAnswer a few questions and see which options fit your situation

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Medical disclaimer: This website is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any treatment. Prices shown are United States self-pay or list prices and vary by insurance and country.