Tirzepatide shows better weight loss results than semaglutide. A major study published in the New England Journal of Medicine found that people using tirzepatide lost 20.2% of their body weight on average, while those using semaglutide lost 13.7%. Both medications help with weight loss, but they work in different ways and have different benefits.

This guide will help you understand how these two popular weight loss medications compare. We’ll cover their effectiveness, side effects, costs, and what makes each one unique. By the end, you’ll know which option might work better for your weight loss goals.

How These Weight Loss Medications Work

What Is Semaglutide?

Semaglutide is a medication that copies a hormone your body makes naturally called GLP-1. This hormone helps control your appetite and blood sugar levels. When you take semaglutide, it:

• Makes you feel full longer after eating
• Slows down how fast food leaves your stomach
• Reduces food cravings
• Helps your body make insulin when needed

The medication comes in different brand names. Ozempic is used for diabetes, while Wegovy is specifically approved for weight loss. You can take semaglutide as a weekly injection or daily pill.

What Is Tirzepatide?

Tirzepatide works on two different hormone systems instead of just one. It targets both GLP-1 and GIP receptors in your body. This dual action means it can:

• Control appetite even better than single-hormone medications
• Improve blood sugar control more effectively
• Lead to greater weight loss in many people
• Help your body use insulin more efficiently

Tirzepatide is sold under the brand names Mounjaro for diabetes and Zepbound for weight loss. It’s only available as a weekly injection.

Weight Loss Effectiveness: Which Works Better?

Clinical Trial Results

The most recent head-to-head study showed tirzepatide provided 47% greater relative weight loss compared to semaglutide. On average, tirzepatide led to 20.2% weight loss compared to 13.7% with semaglutide over 72 weeks of treatment.

A comprehensive analysis published in JAMA Internal Medicine confirmed these findings in real-world clinical settings, showing that tirzepatide consistently outperformed semaglutide for weight loss across different patient populations.

Here’s what the research shows for weight loss:

Tirzepatide Results:

• Average weight loss: 15-21% of starting body weight
• Up to 65% of people lost 10% or more of their weight
• About 31% of people lost 20% or more of their weight

Semaglutide Results:

• Average weight loss: 13-16% of starting body weight
• Around 73% of people lost 5% or more of their weight
• About 58% of people lost 10% or more of their weight

Real-World Results

In real-world clinical settings, people taking tirzepatide were more likely to achieve significant weight loss milestones compared to those taking semaglutide. This matches what researchers found in controlled studies.

The bigger weight loss with tirzepatide likely happens because it works on two hormone systems instead of one. This gives it more ways to control appetite and help your body manage weight.

Side Effects Comparison

Common Side Effects for Both Medications

Both semaglutide and tirzepatide can cause similar side effects, mainly stomach-related issues:

• Nausea (most common)
• Vomiting
• Diarrhea
• Constipation
• Stomach pain
• Loss of appetite

Most side effects are mild to moderate and happen mainly when starting the medication or increasing the dose.

Important Differences in Side Effects

Tirzepatide side effects:

• Tirzepatide tends to cause fewer stomach side effects despite showing more weight loss
• Some people find it easier to tolerate than semaglutide
• Higher doses may increase the chance of stomach upset

Semaglutide side effects:

• May cause more pronounced nausea for some people
• Side effects often improve as your body gets used to the medication
• Generally well-tolerated when doses are increased slowly

Serious Side Effects to Know About

Both medications have important safety warnings from the FDA:

• Both have boxed warnings about the risk of thyroid C-cell tumors
• Don’t use if you have a personal or family history of certain thyroid cancers
• Can cause inflammation of the pancreas (rare but serious)
• May slow stomach emptying too much in some people

Cost and Insurance Coverage

Brand Name Medication Costs

Weight loss medications can be expensive without insurance. According to the Peterson-KFF Health System Tracker, U.S. prices are significantly higher than other countries:

• Wegovy (semaglutide): Around $1,349 per month in the U.S.
• Zepbound (tirzepatide): About $1,023 per month in the U.S.

Studies suggest tirzepatide may offer better value for money because of its higher effectiveness for weight loss over time.

Insurance Coverage Challenges

Most insurance plans don’t cover these medications for weight loss alone. However, they may cover them if you have:

• Type 2 diabetes
• Heart disease
• High blood pressure
• Other weight-related health conditions

More Affordable Options

Both drug companies now offer programs to help lower costs:

• Patient assistance programs for those who qualify
• Direct-to-consumer pricing (often lower than retail)
• Some telehealth companies offer compounded versions

At Yorktown Health’s GLP-1 weight loss program, we help patients find affordable options and work with insurance when possible.

Dosing and How to Take Them

Semaglutide Dosing

For weight loss (Wegovy):

• Start: 0.25 mg weekly for 4 weeks
• Increase gradually to 2.4 mg weekly
• Take as injection under the skin once per week
• Also available as daily pill (Rybelsus) for diabetes

Tirzepatide Dosing

For weight loss (Zepbound):

• Start: 2.5 mg weekly for 4 weeks
• Can increase up to 15 mg weekly
• Take as injection under the skin once per week
• Only available as injection, not as pills

Both medications work best when you increase the dose slowly. This helps your body get used to the medication and reduces side effects.

Who Should Consider Each Medication?

Semaglutide May Be Better If You:

• Want a medication with longer track record and more research
• Prefer having the option of pills instead of injections
• Have diabetes and need proven heart benefits
• Experience fewer side effects with single-hormone approach

Semaglutide has proven cardiovascular benefits and can reduce the risk of heart attack and stroke in people with diabetes.

Tirzepatide May Be Better If You:

• Want potentially greater weight loss results
• Can tolerate the higher starting dose
• Don’t mind that it’s a newer medication with less long-term data
• Have tried semaglutide but want better results

When to Avoid These Medications

Don’t use either medication if you have:

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2
• Severe kidney disease
• Active gallbladder disease
• History of pancreatitis

Making the Right Choice for You

Questions to Ask Your Doctor

Before starting either medication, discuss:

1. Your weight loss goals and timeline
2. Other health conditions you have
3. Medications you’re currently taking
4. Your budget and insurance coverage
5. Whether you prefer pills or injections

Getting Started Safely

Both medications require medical supervision. Your doctor will:

• Check if you’re a good candidate
• Start you on the lowest dose
• Monitor your progress and side effects
• Adjust your dose gradually
• Watch for any complications

At Yorktown Health, our team provides complete care for patients using these medications. We help with weight management through regular check-ups and support.

Lifestyle Changes Still Matter

Diet and Exercise Are Key

Even with these powerful medications, healthy habits are still important:

• Eat a balanced diet with plenty of protein
• Stay active with regular exercise
• Drink enough water throughout the day
• Get adequate sleep each night
• Manage stress in healthy ways

Long-Term Success

Research shows these medications work best when combined with lifestyle changes. The medication helps control your appetite, but building healthy habits ensures long-term success.

What to Expect When Starting Treatment

First Few Weeks

• Start with the lowest dose to minimize side effects
• Some nausea is normal but should improve
• You may notice reduced appetite quickly
• Weight loss usually starts within the first month

Ongoing Treatment

• Doses are increased every 4 weeks until you reach your target
• Most people see steady weight loss over 6-12 months
• Regular check-ups help monitor progress and side effects
• Some people need to try different doses to find what works best

Future of Weight Loss Medications

The success of semaglutide and tirzepatide has led to more research in this area. According to a recent analysis in Healio Endocrinology, these medications significantly outperform other FDA-approved weight loss drugs. The FDA continues to monitor these medications and has resolved previous shortages, making them more available to patients who need them.

Scientists are working on:

• New medications that work on additional hormone pathways
• Longer-lasting formulations
• Combinations of different approaches
• Ways to make treatment more affordable

Final Thoughts

Both semaglutide and tirzepatide are powerful tools for weight loss, but they work differently and have different benefits. Tirzepatide appears to provide greater weight loss for many people, while semaglutide has a longer track record and proven heart benefits.

The best choice depends on your individual situation, health conditions, and goals. Work with a healthcare provider who understands these medications to create a plan that’s right for you.

Remember that sustainable weight loss takes time and effort. These medications can be incredibly helpful, but they work best as part of a complete approach that includes healthy eating, regular activity, and ongoing medical care.

If you’re considering weight loss medication, contact Yorktown Health to learn more about our comprehensive approach to weight management. Our experienced team can help you understand your options and create a personalized plan for lasting success.

Always consult with a qualified healthcare provider before starting any weight loss medication. This information is for educational purposes and should not replace professional medical advice.