Orlistat vs Phentermine: Which Is Best for Weight Loss?

Phentermine vs Orlistat: How Do They Compare?

If you’ve been exploring weight loss medications, chances are orlistat and phentermine have come up more than once. Both are FDA-approved, have decades of clinical use, and may support weight loss for some individuals when paired with diet and exercise. But that’s where the similarities end. 

From how they work in your body to their side-effect profiles, orlistat vs. phentermine is a comparison of two very different approaches. 

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What Is Orlistat? 

Orlistat is a lipase inhibitor. This means it blocks roughly 30% of the dietary fat you consume from being absorbed. This undigested fat passes through your body and is excreted via your bowel movements.

It comes in two forms:

1. Xenical® (120 mg): This is a prescription-strength version FDA-approved in 1999. It’s typically taken three times daily with fat-containing meals.
2. Alli® (60 mg): This is a lower-dose, over-the-counter version of orlistat that became available in 2007, making it one of the few weight loss medications you can purchase without a prescription.

Orlistat is generally prescribed for adults with a BMI of 30 or higher, or 27 or higher with at least one weight-related condition. Because orlistat can reduce the absorption of fat-soluble vitamins (A, D, E, and K), most providers recommend taking a daily multivitamin as well.

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What Is Phentermine?

Phentermine is a sympathomimetic amine that works on your central nervous system, specifically by increasing norepinephrine levels in the brain. In turn, this may help reduce hunger signals and, for some people, lead to increased energy, which some individuals find helpful when following a reduced-calorie eating plan.

Phentermine has been available since 1959, making it one of the longest-standing weight-loss medications on the market. It’s typically taken once daily (15-37.5 mg) before breakfast or one to two hours after. Because of its stimulant properties, the FDA classifies phentermine as a Schedule IV controlled substance, and it’s generally prescribed for short-term use, usually up to 12 weeks.

Like orlistat, phentermine is intended for adults with a BMI of 30 or above, or 27 or above with a weight-related health condition such as high blood pressure, type 2 diabetes, or high cholesterol.

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‍Side Effects: Orlistat vs Phentermine 

Both medications come with potential side effects, but they look very different depending on which one you’re taking.

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Orlistat Side Effects 

Because orlistat works by blocking fat absorption, the most common side effects are gastrointestinal. These can include oily or fatty stools, gas, stomach discomfort, and, in some cases, fecal urgency. These effects tend to be more noticeable in the first few months of treatment and often improve over time, especially when paired with a reduced-fat diet. 

In rare cases, orlistat has been associated with liver injury and kidney issues, so it’s important to stay in touch with your provider.

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Phentermine Side Effects

Phentermine’s side effects reflect its stimulant nature. Dry mouth is the most commonly reported, followed by insomnia, headaches, increased heart rate, and feelings of restlessness or anxiety. 

Since it affects the central nervous system, phentermine isn’t recommended for people with cardiovascular disease, uncontrolled high blood pressure, hyperthyroidism, glaucoma, or a history of substance abuse. A licensed healthcare provider can help you weigh these factors based on your health history.

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Orlistat vs Phentermine: Key Differences 

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Final Thoughts 

Both orlistat and phentermine work best alongside healthy eating habits, regular movement, and ongoing support from a healthcare provider. Medication is one tool in a much bigger picture—and the best results tend to come from a comprehensive approach. 

If you’re not sure where to start, Eden can help simplify the process. Begin with a quick online intake and connect with a licensed healthcare provider who will review your health history, goals, and lifestyle to determine which medication (if any) is the right fit for you. If treatment is appropriate, your provider will create an individualized plan, and your medication will ship directly to your door through a licensed pharmacy. But our support doesn’t end there; you’ll also have access to 24/7 provider messaging and ongoing check-ins from your care team so you’re never navigating the journey alone.