Tirzepatide vs. Semaglutide: What You Should Know

By now, you’ve probably heard a lot about GLP-1 agonists, like Ozempic®, Wegovy®, Mounjaro® and Zepbound®.

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But when it comes to the different types of GLP-1s, like tirzepatide vs. semaglutide, what’s the difference?

Endocrine clinical pharmacist Diana Isaacs, PharmD, explains how each works.

Differences between semaglutide and tirzepatide, GLP-1s

Tirzepatide vs. semaglutide

It can be confusing to know whether tirzepatide or semaglutide will benefit you and your health. While similar, they differ in how they work and how they’re dosed.

Tirzepatide is approved by the U.S. Food and Drug Administration (FDA) for:

Type 2 diabetes in adults and children 10 years or older
Weight management
Moderate-to-severe obstructive sleep apnea in adults with obesity

Semaglutide is approved by the FDA for:

Type 2 diabetes
Weight management in adults and children 12 years or older
Cardiovascular risk reduction in adults with Type 2 diabetes and established heart disease

How each one works

Let’s dive into how each medication works.

How semaglutide works

Semaglutide medications, like Ozempic, Rybelsus® and Wegovy, work by mimicking a hormone known as glucagon-like peptide-1 (GLP-1). When you eat, the hormone triggers the production of insulin and sends your brain signals that you’re full.

Semaglutide can:

Improve blood sugar
Increase insulin sensitivity
Slow stomach emptying
Reduce appetite
Aid in weight loss
Reduce body fat

Semaglutide is available as a daily oral pill or a weekly injectable medication.

How tirzepatide works

While semaglutide works to mimic GLP-1 hormones, tirzepatide (like Mounjaro and Zepbound) is considered a dual agonist. It increases GLP-1 and another hormone called glucose-dependent insulinotropic polypeptide (GIP)

This means it works in two ways — while semaglutide only mimics GLP-1 hormones, tirzepatide also mimics GIP hormones. Like GLP-1 hormones, GIP hormones are triggered when you eat and increase insulin production.

Tirzepatide can:

Improve blood sugar
Increase insulin sensitivity
Slow stomach emptying
Reduce appetite
Aid in weight loss
Reduce body fat

Currently, tirzepatide is only available as a once-a-week injectable medication.

Tirzepatide vs. semaglutide for weight loss

Both can be effective in weight loss, but in head-to-head trials, tirzepatide has a slight edge over semaglutide. It had more weight loss and glucose-lowering, although researchers didn’t use the highest dose of semaglutide when comparing the two.

“Typically, tirzepatide is superior for glucose-lowering and for weight loss,” reinforces Dr. Isaacs. “We’ve also seen this from real-world data. If someone is on semaglutide and we switch them to tirzepatide, often, they’re going to experience more weight loss.”

But she notes that the response can vary from person to person. And some people have fewer side effects on one drug versus another.

Tirzepatide vs. semaglutide side effects

While they may work differently, tirzepatide and semaglutide both share common digestive side effects, like:

Nausea and vomiting
Diarrhea
Constipation
Abdominal pain
Heartburn

Other side effects may include:

Fatigue
Headaches
Low blood sugar (hypoglycemia) if taken with other medications that can cause hypoglycemia, like insulin or sulfonylureas

Dr. Isaacs says that while most people can safely take a GLP-1, you should avoid it if you have severe gastroparesis (stomach paralysis). Both tirzepatide and semaglutide come with boxed warnings from the FDA (the strongest safety warning for prescription drugs) about the risk of developing thyroid C-cell tumors.

“This particular form of cancer is genetic, so if someone has a family history, they’re already at an increased risk,” she explains.

These medications also aren’t recommended during pregnancy.

Which is the right choice for you?

The best thing you can do is have a conversation with a healthcare provider. They can take your medical history and other factors into consideration — and help you determine which GLP-1 may be the right fit for you.

Overall, it’s important to understand the benefits and risks of taking a GLP-1 and to know that it’s not a quick fix. You will also need to focus on lifestyle changes, like physical activity and healthy eating.

“Tirzepatide and semaglutide are meant to be long-term medications,” stresses Dr. Isaacs. “Obesity is a chronic condition, just like diabetes. When you stop taking either drug, your blood sugar may rise and you may gain weight. Healthy lifestyle changes can help a lot, though. ”