Tirzepatide vs. semaglutide: Differences & similarities explained

In this article:

• What is tirzepatide?
• What is semaglutide?
• Key differences
• Conditions treated
• Cost & coverage
• Side effects
• Drug interactions & warnings
• Which is best for weight loss?

In this article

• What is tirzepatide?
• What is semaglutide?
• Key differences
• Conditions treated
• Cost & coverage
• Side effects
• Drug interactions & warnings
• Which is best for weight loss?

Tirzepatide and semaglutide have exploded in popularity over the past few years, primarily due to their weight loss benefits. Tirzepatide is the active ingredient in both Mounjaro and Zepbound, while semaglutide is the active ingredient in Ozempic, Wegovy, and Rybelsus (an oral medicine). These medications act like natural hormones in the body, regulating appetite and reducing food noise (intrusive thoughts about food that interfere with weight loss efforts). While these drugs share some similarities, they also have some differences. 

Note that while there are compounded versions of tirzepatide and semaglutide, these drugs are not FDA approved. This article focuses on the five FDA-approved versions of tirzepatide and semaglutide.

What is tirzepatide?

Tirzepatide is the active ingredient in two medications approved by the Food and Drug Administration (FDA). Mounjaro is FDA approved for Type 2 diabetes but is prescribed off-label (for a non-FDA-approved use) for weight loss. Zepbound is FDA approved for weight loss and obstructive sleep apnea. These medications are given as once-weekly injections subcutaneously (under the skin). Eli Lilly manufactures both Mounjaro and Zepbound. 

What is semaglutide?

Semaglutide is the active ingredient in three FDA-approved medications. Ozempic is used for Type 2 diabetes and cardiovascular risk reduction (lowering the risk of major adverse cardiovascular events, including cardiovascular death, heart attack, and stroke) and is commonly prescribed off-label for weight loss. Wegovy is FDA approved for weight loss and cardiovascular risk reduction. Ozempic and Wegovy are given as once-weekly subcutaneous injections. Rybelsus is a tablet that is taken by mouth once a day. It is FDA approved for Type 2 diabetes. Novo Nordisk manufactures Ozempic, Wegovy, and Rybelsus.

RELATED: How long can you take semaglutide?

Tirzepatide vs. semaglutide: Key differences

Tirzepatide, which is the active ingredient in the brand-name drugs Mounjaro and Zepbound, is classified as a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, also known as a GIP receptor/GLP-1 receptor agonist. Semaglutide is the active ingredient in brand-name injectable drugs Ozempic and Wegovy, as well as the brand-name oral drug Rybelsus. It is classified as a GLP-1 receptor agonist. 

Compare tirzepatide vs. semaglutide key differences

	Tirzepatide	Semaglutide
Drug class	GIP/GLP-1 agonist	GLP-1 agonist
Brand/generic status	Brand	Brand
What is the brand name?	Mounjaro Zepbound	Ozempic Rybelsus Wegovy
What form(s) does the drug come in?	Injection	Ozempic and Wegovy: Injection Rybelsus: Oral tablet
What is the standard dosage?	Starting dose: 2.5 mg injected once a week. The healthcare provider will gradually increase the dose to a maximum of 15 mg injected once a week. Doses may vary based on condition, response to treatment, and side effects.	Starting dose of Ozempic and Wegovy: 0.25 mg injected once a week. The healthcare provider will gradually increase the dose to a maximum of 2 mg (Ozempic) or 2.4 mg (Wegovy) injected once a week. Doses may vary based on condition, response to treatment, and side effects. Starting dose of Rybelsus: There are two formulations. One formulation has a starting dose of 3 mg per day, with the dose gradually increased up to a maximum of 14 mg per day. The second formulation has a starting dose of 1.5 mg per day, with the dose gradually increased up to a maximum of 9 mg per day.
How long is the typical treatment?	Long-term	Long-term
Who typically uses the medication?	Adults	Ozempic, Rybelsus: Adults Wegovy: Adults and pediatric patients 12 years and older

 

Tirzepatide vs. semaglutide: Conditions treated

Tirzepatide is the active ingredient in both Mounjaro and Zepbound.

• Mounjaro is FDA approved to help control blood sugar levels in adults with Type 2 diabetes. It is often prescribed off-label for weight reduction. 
• Zepbound is FDA approved for weight loss and long-term maintenance of weight loss in adults with obesity, or adults who are overweight with at least one weight-related medical condition, such as high blood pressure or high cholesterol. It is also FDA approved for moderate to severe obstructive sleep apnea in adults with obesity. Obesity generally includes people with a body mass index, or BMI, of 30 or above.

Semaglutide is the active ingredient in Ozempic, Wegovy, and Rybelsus. 

• Ozempic is FDA approved for Type 2 diabetes. It is also FDA approved to reduce cardiovascular risk in adults with both Type 2 diabetes and heart disease. Ozempic is often prescribed off-label for weight loss. 
• Wegovy is FDA approved for weight loss and long-term weight maintenance in adults and pediatric patients 12 years and older with obesity, as well as adults who are overweight and have at least one weight-related health condition. It is also used to reduce cardiovascular risk in adults who have heart disease and either have obesity or are overweight.
• Rybelsus is FDA approved for Type 2 diabetes and is sometimes prescribed off-label for weight loss. 

Healthcare providers often recommend patients combine lifestyle changes with these medications, including a reduced-calorie diet and increased physical activity.

Tirzepatide vs. semaglutide cost & coverage

Since tirzepatide and semaglutide are active ingredients of brand-name drugs with no generic versions, the only way to compare prices is by looking at the brand-name drugs. Note that drug prices fluctuate and vary by pharmacy, and insurance coverage will vary by drug and condition treated. For example, some insurance plans may not cover a Type 2 diabetes drug, like Ozempic, when used off-label for weight loss. You can contact your insurance provider for the most recent information on coverage, as well as pricing estimates. You can use a free SingleCare card or coupon to save on any of these prescriptions. Here are some examples of savings: 

• Without insurance, a one-month supply of Zepbound 2.5 mg injections costs about $1,503, but you can pay as low as $947 with a free SingleCare coupon.
• A one-month supply of 2 mg Ozempic costs about $1,343, but a free SingleCare coupon can bring the price down to as low as $811.

Compare tirzepatide vs. semaglutide cost and coverage

	Mounjaro (tirzepatide)	Zepbound (tirzepatide)	Ozempic (semaglutide)	Rybelsus (semaglutide)	Wegovy (semaglutide)
Typically covered by insurance?	Coverage Varies by plan	Coverage Varies by plan	Coverage Varies by plan	Coverage Varies by plan	Coverage Varies by plan
Typically covered by Medicare Part D?	Coverage varies by plan	Coverage varies by plan	Coverage varies by plan	Coverage varies by plan	Coverage varies by plan
Quantity	4 syringes of 5 mg injections (one-month supply)	4 syringes of 2.5 mg injections (one-month supply)	1 pen containing a one-month supply of 2 mg injections	30, 7 mg tablets	1 pen containing a one-month supply of 2.4 mg injections
SingleCare cost*	$872	$947	$811	$873	$1,216

*Cost at time of publication. Drug prices fluctuate and vary by pharmacy.  

Tirzepatide vs. semaglutide side effects

Tirzepatide and semaglutide commonly cause gastrointestinal side effects. The most common side effects of all five FDA-approved drugs include:

• Nausea
• Vomiting
• Diarrhea or constipation
• Stomach pain

Other side effects that may occur include:

• Indigestion
• Gas/burping
• Bloating
• Tiredness
• Low blood sugar
• Decreased appetite 
• Hair loss 
• Injection site reactions (not applicable to Rybelsus, which is taken by mouth)

Symptoms of a serious allergic reaction, such as hives, trouble breathing, or swelling of the face, lips, tongue, or throat, require emergency medical help. 

Side effects will vary by drug and dosage. This is not a full list of side effects, and others may occur. Consult your healthcare professional for more information and a full list of side effects. 

Tirzepatide and semaglutide drug interactions

Before using tirzepatide or semaglutide, tell your healthcare provider about all the medications you take, including prescription and OTC drugs, vitamins, and supplements. Semaglutide and tirzepatide have some similar drug interactions to be aware of: 

• There is an increased risk of hypoglycemia (low blood sugar), including severely low blood sugar, when using tirzepatide or semaglutide along with insulin or certain types of diabetes drugs, such as sulfonylureas. Tell your healthcare provider if you use insulin or take any medicine for diabetes. You may need a dosage adjustment and close monitoring. 
• Tirzepatide and semaglutide affect gastric emptying, which may affect medicines that are taken by mouth. Consult your healthcare provider for medical advice regarding other medicines you take. If you are using birth control pills, you should use a non-oral form of birth control (such as condoms) or add a barrier method for one month after beginning treatment with tirzepatide and for one month following each dose increase.

Consult your healthcare provider for more information about drug interactions and how they may affect you. 

Tirzepatide and semaglutide drug warnings

Tirzepatide and semaglutide medications have a black box warning, which is the most serious warning required by the FDA. The warning states that these medications have caused thyroid cancer in animal studies. It is not known whether this applies to humans. However, if you have a personal or family history of medullary thyroid carcinoma (MTC) or you have multiple endocrine neoplasia syndrome type 2 (MEN 2), you should not use tirzepatide or semaglutide. While using tirzepatide or semaglutide, you should be alert to symptoms of thyroid cancer, such as difficulty breathing or swallowing, a hoarse voice, or a lump in the neck. Report any symptoms to your healthcare provider right away. 

Tirzepatide and semaglutide, in rare cases, may cause serious side effects, which include:

• Pancreatitis (inflammation of the pancreas)
• Vision problems
• Kidney problems, including kidney failure
• Gallbladder problems
• Pulmonary aspiration during sedation or procedures (tell your healthcare provider you use tirzepatide or semaglutide if you are planning any medical procedures)

Before using tirzepatide or semaglutide, tell your healthcare provider about all of your medical conditions, medical history, and family history. 

Which is best for weight loss? 

While you may see effective weight loss with any of these medications, a 2024 clinical trial compared tirzepatide versus semaglutide over 72 weeks. The researchers found that people who used tirzepatide had greater weight loss (20.2% of body weight) than those who used semaglutide (13.7% of body weight). This does not necessarily mean that tirzepatide will be the best option for everyone, as both drugs are effective—and different people respond differently to each drug. Consult your healthcare provider for medical advice. 

Bottom line

Tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy, Rybelsus) are used to treat conditions such as Type 2 diabetes and sleep apnea and are also often used for weight loss (whether FDA-approved or off-label). Consult your healthcare provider for more information and medical advice about which drug is best for you.