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Zepbound vs Xenical

Quick read · 5 min

Last reviewed: September 2026Based on 2 clinical trialsEvery claim linked to source

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
 ZepboundXenical
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–$1,086/mowith the manufacturer savings programme; list ~$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–$1,086/mo

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

Self-pay vials via LillyDirect from $299/month (2.5 mg) to $699/month (10–15 mg), per zepbound.lilly.com on 4 September 2026; list price ~$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–$1,086/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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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.