Introduction

Looking to lose weight with the help of a prescription? You’ve likely come across Zepbound, one of the newest hormone-based weight loss injections, and Orlistat, a long-time fat blocker available over the counter and by prescription as Alli or Xenical.

Though both are FDA-approved for weight loss, they work very differently. One alters how your body absorbs fat, while the other changes how your brain and gut regulate hunger.

In this blog, we compare Zepbound vs Orlistat in plain English to help you decide which approach is best for your goals.

Quick Comparison

Feature	Zepbound	Orlistat (Alli/Xenical)
FDA Approved For	Obesity (2023)	Obesity (1999)
How It Works	Appetite suppression via hormones	Blocks fat absorption in intestines
Average Weight Loss	15–22.5% of body weight	5–7% of body weight
Dosing Format	Weekly injection	3x daily pill with meals

Zepbound changes how you feel hunger. Orlistat changes how your body absorbs fat.

How Each Medication Works

Zepbound (tirzepatide)

• Mimics GLP-1 and GIP gut hormones
• Suppresses appetite
• Slows digestion
• Helps your body burn more fat
• Reduces insulin resistance

Orlistat

• Inhibits pancreatic lipase, the enzyme that digests fat
• About 30% of dietary fat passes through your digestive system unabsorbed
• Doesn’t affect hunger or metabolism

Weight Loss Comparison

Medication	Avg. Weight Loss	Study Reference
Zepbound	Up to 22.5%	SURMOUNT-1 Trial
Orlistat	5–7%	Xenical Trials

Zepbound produces 3–4x greater fat loss, especially in patients with insulin resistance or obesity.

Side Effects

Side Effect	Zepbound	Orlistat
Nausea	Common (early weeks)	Rare
Digestive Issues	Constipation	Oily stools, gas, diarrhea
Appetite Suppression	Strong	None
GI Accidents	Uncommon	Very common

Orlistat’s most common complaints include uncontrolled bowel movements and urgency, especially if you eat a high-fat meal.

Dosing & Convenience

Zepbound

• Weekly injection
• Simple pen device
• Doesn’t depend on what or when you eat

Orlistat

• Take a pill with every fat-containing meal (up to 3x/day)
• Requires low-fat diet for tolerability
• Over-the-counter (Alli) version is lower strength

Zepbound is simpler and more flexible, while Orlistat requires meal-by-meal planning.

Cost & Coverage

Factor	Zepbound	Orlistat (Xenical or Alli)
FDA Approved	For chronic weight management	For obesity
Prescription Required	Yes	Only for Xenical version
Retail Cost	~$1,060/month	~$30/month (Alli), ~$100/month (Xenical)
Savings Card	Zepbound Card	Alli Info

Orlistat is far cheaper, but comes with more digestive side effects and less weight loss.

Who Should Use Zepbound?

Ideal for:

• Individuals with 20+ lbs to lose
• Those struggling with appetite, cravings, or insulin resistance
• Patients who want long-term hormonal support
• Anyone looking for a once-a-week routine

Who Might Use Orlistat?

Consider if:

• You’re looking for an affordable, non-injection option
• You only need to lose a modest amount of weight
• You prefer to avoid hormonal or appetite-based medications
• You’re already eating a very low-fat diet

Can They Be Combined?

Not typically necessary.

Combining Zepbound and Orlistat offers minimal added benefit and may increase GI side effects. Most providers recommend using one or the other—not both.

Final Thoughts

Both Zepbound and Orlistat can support weight loss, but they are very different tools.

Zepbound = stronger weight loss, hormone-based, fewer lifestyle restrictions
Orlistat = lower cost, non-hormonal, but GI side effects may limit use

Visit our Weight Loss Medication Finder to get personalized guidance, compare options side-by-side, and connect with licensed providers.