Phentermine vs semaglutide: Which weight loss medication is right for you?

Key points

• Phentermine suppresses appetite short-term, and semaglutide works long-term
• Semaglutide achieves an average of 15%-20% weight loss versus phentermine's 5-10%
• Phentermine acts fast but has heart risks, and semaglutide has digestive side effects
• Both need diet and lifestyle changes to work effectively

When you're in your doctor's office discussing weight loss medications, two names may come up: phentermine and semaglutide.

One's been America's go-to appetite suppressant since 1959. The other arrived more recently as a weekly injection promising weight loss, blood sugar control, and heart health.

But which one works best for lasting weight loss? Let’s take a look.

What is phentermine? How does it work?

Phentermine has been around since 1959, and it is a stimulant prescribed for short-term weight loss. Because it's similar to amphetamines, phentermine is a controlled substance. Doctors typically prescribe it for 12 weeks at a time to minimize the risk of dependency.

Gia Eapen, MD, elaborates, “It works by raising brain chemicals like norepinephrine and dopamine, which help control hunger signals and food cravings. Along with reduced appetite, users often feel more energized and focused, making it easier to maintain an active lifestyle and reach their weight loss goals.”

The FDA approved phentermine in adults aged 17 and older, typically for those with a BMI of 30 or higher, or 27 or higher with weight-related conditions. Common brand names include Adipex-P and Lomaira. Qsymia combines phentermine with topiramate for chronic weight management.

What is semaglutide? How does it work?

Semaglutide (Wegovy, Ozempic, Rybelsus) takes a different approach from phentermine. The biggest difference is that semaglutide is not a stimulant.

It works by slowing digestion, helping you feel full faster and for longer. It reduces hunger by stimulating the brain's appetite center. It also promotes insulin release during meals, which helps control blood sugar.

Semaglutide is available in different versions:

• Wegovy: A weekly injectable approved for weight loss in adults and children aged 12 and older with obesity.
• Ozempic and Rybelsus: Approved for type 2 diabetes management in people with obesity. However, they are sometimes prescribed off-label for weight loss. Ozempic is a once-weekly injection, while Rybelsus is a pill form of semaglutide.

In general, injectable semaglutide tends to be more effective than the oral version because it delivers higher and more consistent levels of the medication in the body.

Phentermine vs. semaglutide: Weight loss

Semaglutide delivers stronger, longer-lasting weight loss than phentermine, though it costs more and requires injections. Phentermine works faster and costs less, but is only for short-term use.

Semaglutide weight loss

Studies show semaglutide helps people lose 15-20% of their body weight over several months. It's designed for ongoing use and provides blood glucose control and cardiovascular benefits.

Disadvantages of semaglutide include the fact that they are weekly injection (except the oral form, Rybelsus), higher costs, and side effects.

Phentermine weight loss

Phentermine suppresses appetite quickly and costs less, but it produces more modest results of 5-10% weight loss.

Additionally, since it is a stimulant, it can't be used long-term due to potential side effects and the risk of dependence. Doctors typically limit use to 12 weeks or less.

Phentermine vs. semaglutide: Blood sugar management

Semaglutide has direct, measurable effects on blood sugar regulation and is used as a diabetes medication. Phentermine's effects on blood sugar are indirect, primarily through weight loss rather than metabolic action.

Semaglutide and blood sugar levels

Semaglutide directly improves blood sugar control in several ways. It stimulates insulin release after meals while suppressing glucagon, a hormone that raises blood sugar. The medication also slows digestion to prevent post-meal glucose spikes.

The FDA has approved semaglutide for the treatment of type 2 diabetes under the brand names Ozempic and Rybelsus. People taking semaglutide typically see lowered A1c levels, which measure average blood sugar over three months.

Phentermine is not approved to treat diabetes and works differently from diabetes medications. Unlike semaglutide, it doesn't directly affect insulin or blood sugar mechanisms.

Any blood sugar improvements come indirectly through weight loss, which helps the body respond better to insulin. However, because phentermine is a stimulant, it may raise blood sugar through stress hormones. People with diabetes need careful monitoring while taking it.

Phentermine vs. semaglutide: Side effects

Knowing potential side effects helps you prepare and make informed decisions.

Phentermine side effects

Phentermine's side effects come from its stimulant properties. Common issues include dry mouth, trouble sleeping, headaches, and jitteriness. Some people experience elevated heart rate and blood pressure. High doses may cause overstimulation or irritability.

Eapen, MD, says, “Dependency and withdrawal symptoms are more serious concerns. People with heart disease, hyperthyroidism, glaucoma, or uncontrolled hypertension should not take phentermine. Rare cases have involved serious heart valve problems and dangerously high blood pressure.”

Semaglutide side effects

Semaglutide primarily affects the digestive system.

Common semaglutide side effects are typically digestive, including nausea, vomiting, diarrhea, constipation, stomach pain, and bloating. These symptoms usually improve as your body adjusts. Starting with a low dose and increasing gradually helps minimize discomfort.

Rare but serious side effects include pancreatitis, gallbladder problems, and kidney issues.

Semaglutide carries a warning about thyroid tumors found in animal studies. This has not been confirmed in humans. People with a personal or family history of certain thyroid cancers should talk to their healthcare provider.

Final thoughts: Phentermine vs. semaglutide?

Both phentermine and semaglutide can help with weight loss, but they work differently and suit different needs.

Phentermine is a short-term weight loss drug. It is only prescribed for about 12 weeks.

Semaglutide, on the other hand, leads to greater weight loss and can be used long-term if required. It also directly lowers blood sugar levels and even lowers the risk of heart attacks and stroke in people with a high risk of heart disease.

Consult your healthcare provider about which option fits your needs. Medication alone is not enough for sustained weight loss or to manage blood glucose levels. A sustainable lifestyle, like a nutritious diet and exercise, is also needed.

Frequently asked questions (FAQs)

Which is better, phentermine or semaglutide?

Neither medication is universally better. Phentermine costs less and works quickly for initial weight reduction. Semaglutide produces more significant results and better maintains those results. It also helps manage blood sugar and reduces cardiovascular risks. Your best choice depends on your health status, goals, and your healthcare provider’s evaluation.

Is phentermine FDA-approved?

Yes, phentermine has been FDA-approved since 1959 and has been widely prescribed as a weight loss drug in the United States. A combination product, Qsymia (phentermine plus topiramate), is also available for extended treatment.

Is semaglutide better than phentermine for weight loss?

Research shows semaglutide produces greater weight reduction in clinical trials. Studies also suggest it supports longer-term use compared to phentermine, which has a limited treatment duration.

However, "better" depends on individual circumstances. Phentermine may be more appropriate for some people based on medical history and treatment goals.

What is safer, phentermine or Wegovy?

Both medications are generally safe when used as prescribed, but they have different risk profiles. Phentermine carries risks of dependency, elevated heart rate, and increased blood pressure. It's not safe for people with heart disease or certain other conditions. Semaglutide (Wegovy, Ozempic, and Rybelsus) has primarily digestive side effects that usually improve over time. It's approved for long-term use and shows cardiovascular benefits in people with heart disease. Your doctor will determine which is safer based on your specific health situation.

What is more powerful than semaglutide for weight loss?

Tirzepatide (marketed as Zepbound for weight loss and Mounjaro for diabetes) is currently the most effective weight loss medication available. It's a dual GLP-1 and GIP receptor agonist. This means it activates two hormone pathways instead of one. Semaglutide only activates the GLP-1 pathway.

How to sustain weight loss on phentermine or semaglutide?

Weight loss medications help reduce appetite and jumpstart your progress, but they are only the first step. Sustainable weight loss requires the right nutritious diet tailored to your needs.

Get your personalized weight loss plan with a registered dietitian who accepts your insurance.

The views expressed by authors and contributors of such content are not endorsed or approved by Fay and are intended for informational purposes only. The content is reviewed by Fay only to confirm educational value and audience interest. You are encouraged to discuss any questions that you may have about your health with a healthcare provider.