Tirzepatide vs. semaglutide: A complete comparison guide

Key Points

• Tirzepatide works on two hormone pathways (GLP-1 and GIP) while semaglutide targets one pathway (GLP-1) that reduces appetite and controls blood sugar levels
• In a direct comparison, tirzepatide helped people lose more weight, on average
• Both medications require weekly injections and have similar side effects, like nausea and digestive issues
• Additionally, semaglutide has FDA approval for heart protection benefits, while tirzepatide is approved for sleep apnea treatment

Both tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) are transforming how doctors treat type 2 diabetes and obesity, but they're not identical medications.

If you're trying to understand which one offers better results for your health goals and how to make an informed decision between them, this article breaks down the key differences.

Here's what you need to know about how these medications compare for weight loss, diabetes management, side effects, and costs.

Tirzepatide vs Semaglutide: How do they work?

How does tirzepatide work?

Tirzepatide is available under two FDA-approved brand names: Mounjaro for type 2 diabetes and Zepbound for chronic weight management.

Tirzepatide works by mimicking two hormones that:

• Reduce your appetite
• Lower blood sugar levels

When you eat, your intestines naturally release hormones, called GLP-1 and GIP, which signal your brain when you're full and help your pancreas manage blood sugar levels.

"Tirzepatide is unique because it activates both GLP-1 and GIP hormone pathways at the same time," explains Eapen, MD. "In contrast, most other GLP-1 medications, like Ozempic, target one pathway."

"Semaglutide mimics the GLP-1 hormone, which plays a crucial role in blood sugar regulation and appetite control," notes Eapen, MD. "When you eat, GLP-1 helps your body release insulin, slows down digestion, and signals to your brain that you're full. Semaglutide amplifies these processes.”

Tirzepatide vs. semaglutide: Weight loss

When it comes to weight loss, both medications have shown effectiveness in clinical trials, although tirzepatide appears to have an advantage based on what the research shows so far.

Research shows that tirzepatide has slightly better weight loss results than semaglutide.

In the study, people with obesity (but without diabetes) were followed for over a year. 

The results:

• People taking tirzepatide lost an average of 20.2% of their body weight
• Those on semaglutide lost 13.7%.

To put that in perspective, a person with a starting weight of 240 pounds lost 50 pounds with tirzepatide compared to 33 pounds with semaglutide.

Please note that everyone responds differently to these medications. What works best in studies might not be what works best for you, so talk to your healthcare provider about your options.

Tirzepatide vs. semaglutide: Type 2 diabetes

For blood sugar control, both tirzepatide and semaglutide appear to be effective, based on current studies. However, with tirzepatide, the dose makes a difference.

Here's what the research shows: Higher doses of tirzepatide (10 mg and 15 mg) were more effective at lowering A1C levels compared to semaglutide. But at the lower 5 mg dose, tirzepatide and semaglutide performed about the same.

This means that if you're considering tirzepatide for diabetes management, higher doses may provide better blood sugar control. However, they may also come with a higher price tag and potentially more intense side effects.

Tirzepatide vs semaglutide: Heart health

“Semaglutide (Wegovy) is FDA approved to help reduce the risk of serious heart problems like heart attacks, strokes, and cardiovascular death in people who already have heart disease and are overweight," explains Eapen, MD. "Tirzepatide is still being studied for these heart benefits, so we don't yet have that same level of data or FDA approval for heart protection."

The research supporting semaglutide's heart benefits shows clear outcomes. Studies have shown that semaglutide reduces the risk of cardiovascular events, such as stroke and heart attack, by around 20% in people who are overweight or obese but do not have a prior history of diabetes.

However, tirzepatide does help you lose weight, and research shows that even a 5-10% weight loss can significantly reduce blood pressure, improve cholesterol levels, and lower the risk of heart disease, even in people with type 2 diabetes.

So, with your healthcare provider’s recommendation about what meds to take, diet, and lifestyle changes, you can begin to reap sustainable weight loss and health benefits.

Tirzepatide vs semaglutide: Sleep apnea

Tirzepatide (Zepbound) is FDA-approved to treat moderate to severe obstructive sleep apnea in people with obesity. Semaglutide, while effective for weight loss, doesn't currently have FDA approval specifically for treating sleep apnea.

Sleep apnea is a serious condition that goes far beyond a snoring problem. This breathing disorder significantly increases the risk of heart failure by 140%, stroke by 60%, and coronary heart disease by 30%. It could even be an early warning that diabetes may be on the way.

Since excess fat in the neck and throat area can obstruct breathing, weight loss becomes a crucial part of treatment.

Tirzepatide vs semaglutide: Dosage

Both medications are given as weekly injections, but they follow different dosing schedules.

Tirzepatide (Zepbound and Mounjaro):

• Starts at 2.5 mg weekly
• Increases gradually in 2.5 mg steps
• Maximum dose: 15 mg weekly

Semaglutide dosing varies by brand:

• Ozempic (for diabetes): Starts at 0.25 mg weekly for 4 weeks, then increases to 0.5 mg, 1 mg, or 2 mg weekly
• Wegovy (for weight loss): Starts at 0.25 mg weekly, increases every 4 weeks until reaching 1.7 mg or 2.4 mg maintenance dose

Your healthcare provider will determine the appropriate starting dose and any necessary adjustments based on your individual needs and how well you tolerate the medication.

Tirzepatide vs semaglutide: Side effects

Both medications share similar side effect profiles, primarily affecting the digestive system. The most common side effects include nausea, vomiting, diarrhea, and constipation.

"The side effects are quite similar between tirzepatide and semaglutide," says Eapen, MD. "Starting with a lower dose and gradually increasing it can help minimize side effects, which is why both medications have a starter dose for a few weeks to learn how they affect your body. Some people may find one medication more tolerable than the other, but this varies from person to person.”

Note: Both carry a boxed warning regarding thyroid C-cell tumors.

Tirzepatide vs semaglutide: Costs

The cost of tirzepatide varies depending on which brand you're prescribed.

Tirzepatide costs

• Zepbound: ~$1,086 per monthly supply
• Mounjaro: ~$1,080 per monthly supply

Semaglutide costs

• Wegovy (weight management): ~$1,349 per monthly supply
• Ozempic (diabetes): ~$997.58 per pen (lasts one month/four doses)

While the list prices for both tirzepatide and semaglutide might seem high, your actual out-of-pocket costs may be much lower, depending on your insurance plan.

Please consult your insurance company and healthcare provider to discuss coverage and determine which medications may be right for you.

Tirzepatide vs semaglutide: Which one’s better?

There is no simple answer to whether tirzepatide or semaglutide is “better.” It really depends on each individual’s situation.

The decision involves multiple factors, including:

• Your specific health conditions and medical history
• Your weight loss or diabetes management goals
• How your body responds to each medication
• Your insurance coverage and cost considerations

Since both medications require a prescription and ongoing medical supervision, your healthcare provider is in the best position to evaluate these factors and help determine which option might work best for you. They can also monitor your progress and make adjustments as needed.

How to lose weight on tirzepatide and semaglutide?

Both tirzepatide and semaglutide can be gamechangers for weight loss and diabetes management, but they're not magic bullets. They work better when combined with healthy eating habits and lifestyle changes.

"These medications work best when people see them as an opportunity to transform their overall lifestyle," notes experienced Registered Dietitian, Rita Faycurry, RD. "The most successful patients combine their medication with healthier eating habits and regular exercise. Working with a registered dietitian can help you develop a sustainable plan that maximizes your results."

A registered dietitian can help you:

• Develop a balanced eating plan that supports your medication
• Learn portion control strategies
• Address any nutritional deficiencies
• Create sustainable habits for long-term success
• Manage side effects of Mounjaro, Wegovy, or other GLP-1 medications
• Help you get the nutrition you need even with a reduced appetite

Final thoughts: Tirzepatide vs. semaglutide

Both tirzepatide and semaglutide represent significant advances in treating type 2 diabetes and supporting weight loss. While tirzepatide showed slightly better weight loss results in clinical trials, both medications can be highly effective when used appropriately.

The decision between these medications should always involve your healthcare provider, who can assess your individual situation and help you make the best choice for your health.

Remember that medications like Mounjaro and Ozempic are just one part of a holistic approach to health that includes diet, exercise, and ongoing medical care.

Find a weight loss 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.