Tirzepatide vs semaglutide for weight loss — a comparison

Weight loss drugs with the active ingredient tirzepatide or semaglutide are increasingly popular for chronic weight management as part of a medication-managed approach to weight loss. And if you’re wondering how tirzepatide vs semaglutide for weight loss compares, you’re in the right place.

In this article, we cover available weight loss medications with tirzepatide (Zepbound) and semaglutide (Wegovy) and compare how these active ingredients work for weight loss. Topics include:

• What are tirzepatide and semaglutide?
• Tirzepatide vs semaglutide for weight loss review — Is tirzepatide better?
• Tirzepatide vs semaglutide weight loss medications at-a-glance
• Tirzepatide vs semaglutide side effects
• Taking both semaglutide and tirzepatide or switching from one to another

What are tirzepatide and semaglutide?

Tirzepatide and semaglutide are the active ingredients in the brand name weight loss drugs Zepbound and Wegovy, respectively. They’re also the active ingredients in type 2 diabetes injectables Mounjaro (tirzepatide) and Ozempic (semaglutide), and the oral pill for type 2 diabetes, Rybelsus (semaglutide). 

Tirzepatide and semaglutide for weight loss are once-weekly injectable medications that are U.S. Food and Drug Administration (FDA)-approved for use in adults with a body mass index (BMI) of:

• 30 or greater 
• 27 or greater who have a weight-related health condition, such as type 2 diabetes, high cholesterol, or high blood pressure 

Semaglutide is also approved for use in adolescents aged 12 and older with a BMI in the 95th percentile for sex and age.

For best results, both tirzepatide and semaglutide should be used as part of a medical weight loss program that includes increased physical activity and a reduced calorie diet. 

What is tirzepatide?

Tirzepatide is known as a dual agonist medication. It works for weight loss by mimicking two hormones that are found naturally in the body — glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP).

After eating, GLP-1 works to stimulate insulin production and slow gut movement, while GIP stabilizes insulin levels. These actions increase blood sugar control and satiety, or feeling full after eating, which causes you to eat less and leads to weight loss. 

Tirzepatide started out as a medication to treat type 2 diabetes under the brand Mounjaro, which was approved by the FDA in 2022. The following year, Zepbound made its debut when the FDA approved it for weight loss. While Mounjaro has been used off-label (to treat something it’s not FDA approved to treat) for weight loss, with Zepbound now available, choose it if using tirzepatide for chronic weight management without type 2 diabetes.

Zepbound is available in 6 different doses — 2.5, 5, 7.5, 10, 12.5, and 15 milligrams. The starting dose is 2.5 milligrams. The tirzepatide dosage is increased every four weeks until a maintenance dose is reached, which is usually 15 milligrams for weight loss, but may be less depending on how it’s tolerated and how well it works. 

What is semaglutide?

Semaglutide is a GLP-1 receptor agonist medication which works for weight loss by mimicking the GLP-1 hormone to stimulate insulin production, inhibit glucagon (a glucose-secreting hormone), and slow gut movement. The overall effect is more stable blood sugar and increased satiety, making you want to eat less. Semaglutide is a single receptor agonist and doesn’t affect the GIP hormone like dual receptor agonist tirzepatide does. 

Semaglutide was originally approved as an injectable medication for the treatment of type 2 diabetes in 2017 under the brand Ozempic made by Novo Nordisk. An oral semaglutide pill, Rybelsus, followed in 2019 and is approved to improve blood sugar in adults with type 2 diabetes when combined with diet and exercise. 

In 2021, semaglutide was approved for weight loss under the Novo Nordisk’s brand name Wegovy. 

Like tirzepatide, semaglutide as Wegovy comes in multiple dosages that are increased every 4 weeks to a maximum tolerated maintenance dose. The 5 available doses are 0.25, 0.5, 1.0, 1.7, and 2.4 milligrams. You’ll start with the 0.25 milligram dose and increase your dosage every 4 weeks until you reach a maintenance dose of 2.4 milligrams, which is the maximum dose you can take.

Like Mounjaro, Ozempic has been used off-label for weight loss. If using semaglutide for weight loss, it’s best to choose Wegovy.

Tirzepatide vs semaglutide for weight loss reviews

Current data shows that both tirzepatide and semaglutide lead to effective weight loss. 

• A clinical trial for tirzepatide reported that patients without type 2 diabetes taking the highest dose (15 milligrams) lost an average of 20.9% body weight over 72 weeks.
• A double-blind trial on semaglutide found that individuals  lost 14.9% of their initial body weight on average in 68 weeks. Participants had obesity or overweight without type 2 diabetes.

Data supports that tirzepatide may be better for weight loss. 

• A trial done to compare tirzepatide to semaglutide in people with type 2 diabetes to determine the effect on participants’ glycated hemoglobin level found that tirzepatide led to more weight loss. 
• A analysis of the SURMOUNT-1 and STEP 1 trial data that intended to compare the monetary value of weight loss on tirzepatide vs semaglutide found that not only did people lose more weight on tirzepatide than semaglutide — 17.8% compared to 12.4% in 72 weeks — it cost more than $5,300 less for 68 weeks of tirzepatide than semaglutide.

No direct comparison study of the tirzepatide and semaglutide specifically for weight loss in people without type 2 diabetes has been completed. But a randomized, controlled study comparing the 2 active ingredients for weight loss is underway and expected to wrap up in 2024. Trial participants are obese or overweight with a weight-related health condition and don’t have type 2 diabetes. 

Patient reviews point to a better experience using tirzepatide. 79% of tirzepatide reviews on drugs.com report a positive experience, giving the medication an overall rating of 8.4 out of 10. Just 53% of semaglutide patients gave it positive reviews for an overall rating of 6.5 out of 10.

Experiences with weight loss injections vary among individuals. Talk to your healthcare provider about whether tirzepatide, semaglutide, or another option  is best for your weight loss journey.

Tirzepatide vs semaglutide weight loss medications at a glance

Tirzepatide vs semaglutide: side effects

Like any medication, tirzepatide and semaglutide can cause side effects. Before starting either,  know the potential risks and side effects. And talk to your healthcare provider if you experience side effects while taking tirzepatide or semaglutide.

Common tirzepatide side effects

The most common side effects of tirzepatide include:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Stomach pain
• Indigestion and/or heartburn
• Gas and/or belching
• Fatigue
• Injection site reactions
• Hair loss

Serious side effects of tirzepatide

Serious side effects reported with tirzepatide use include: 

• Allergic reaction
• Inflammation of the pancreas (pancreatitis)
• Gallbladder problems
• Low blood sugar (hypoglycemia)
• Kidney problems
• Changes in vision
• Severe stomach problems

Reach out to your healthcare provider immediately if you experience these or any other serious side effects while taking tirzepatide. 

Tirzepatide comes with a boxed warning for thyroid cancer. A boxed warning is the FDA’s most serious safety warning. You shouldn’t take tirzepatide if you have a personal or family history of medullary thyroid cancer (MCT) or multiple endocrine neoplasia (MEN) syndrome.

Common semaglutide side effects

Common side effects of semaglutide include: 

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Stomach pain
• Indigestion/heartburn
• Gas/bloating
• Fatigue
• Headache or dizziness
• Runny nose
• Sore throat

Serious side effects of semaglutide

The serious side effects reported with semaglutide use include:

• Allergic reaction
• Inflammation of the pancreas (pancreatitis)
• Gallbladder problems
• Low blood sugar (hypoglycemia)
• Kidney problems
• Changes in vision
• Increased heart rate
• Depression and/or suicidal behavior or thoughts

If you experience any of these side effects or your condition seems life-threatening, reach out to your healthcare provider immediately or call 911.

Semaglutide also comes with a boxed warning for thyroid cancer. Tell your provider if you or a family member have a history of medullary thyroid cancer (MCT) or multiple endocrine neoplasia (MEN) syndrome before taking semaglutide.

Taking both semaglutide and tirzepatide or switching from one to another

Taking semaglutide and tirzepatide together isn’t recommended. Because these weight loss drugs work on similar pathways, using them at the same time can increase the risk of side effects and may not offer any added benefits. 

If you currently take Wegovy and are considering switching to Zepbound, or vice versa, talk to your healthcare provider. They can help decide if the switch is right for you and guide you through the process. It’s important to follow your provider’s instructions when switching medications. You should also report any side effects you experience so your provider can adjust your treatment plan as needed. 

Key takeaway

Tirzepatide and semaglutide are active ingredients in brand name drugs approved for weight loss drugs or people with type 2 diabetes. Both help with weight loss and have similar side effects. Currently available research suggests that Zepbound (tirzepatide) may result in more weight loss than Wegovy (semaglutide). 

Off-label use isn’t recommended for medications containing either ingredient as this has led to shortages for people who need them for type 2 diabetes. Talk to your healthcare provider or local pharmacy about any concerns you have regarding the availability of Zepbound or where to find Wegovy in stock.

If you’re considering medically-supervised weight loss, work with a healthcare provider to determine whether tirzepatide, semaglutide, or another prescription weight loss option is right for you.

Find a provider on Klarity and see what’s best for your weight loss goals

If you’re ready to start your weight loss journey, use the Klarity platform to connect you with a licensed healthcare professional specialized in weight loss and weight management. Find a provider today!

The information provided in this article is for educational purposes only and should not be construed as medical advice. Always seek the guidance of a qualified healthcare professional with any questions or concerns you have regarding your health.

How we reviewed this article: This article goes through rigorous fact-checking by a team of medical reviewers. Reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the author.