Tirzepatide vs Semaglutide for Weight Loss: Complete Comparison Guide
If you’re looking into prescription weight loss options, two medications keep coming up: tirzepatide and semaglutide.
You’ve probably heard they’re both effective GLP-1 medications, and clinical research backs that up when they’re used alongside diet and exercise changes. But here’s the thing: they don’t work exactly the same way, and those differences matter when you’re deciding which one is right for you.
This guide walks through how tirzepatide and semaglutide actually compare. We’ll cover weight loss results from clinical studies, what side effects look like, how dosing works, and what to know if you’re thinking about switching from one to the other.
What’s the Difference Between Tirzepatide and Semaglutide?
Both medications are GLP-1 receptor agonists, but they work differently enough that it may affect your overall results.
How Semaglutide Works
Semaglutide mimics a hormone called GLP-1 (glucagon-like peptide-1) that your body naturally makes after you eat. This hormone tells your brain you’re full, slows down how fast food moves through your stomach, and helps keep your blood sugar steady by triggering insulin release.
How Tirzepatide Works
Tirzepatide is the first medication that targets two hormones instead of one: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). That second hormone, GIP, adds extra metabolic benefits like better insulin response, more efficient fat burning, and increased energy use.
When both hormones are working together, your brain and gut get stronger “I’m full” signals, which means you feel less hungry overall and experience less food noise (those constant thoughts about eating and cravings).
Tirzepatide vs Semaglutide Weight Loss: What the Clinical Data Shows
Clinical trials consistently demonstrate that both medications produce meaningful results when combined with lifestyle changes, but tirzepatide appears to deliver more pronounced outcomes.
Semaglutide Weight Loss Results
The landmark STEP trials evaluated semaglutide’s effectiveness for weight management in adults with obesity or who are overweight. In the STEP 1 trial with 1,961 participants, patients taking 2.4 mg semaglutide weekly alongside reduced caloric intake and increased physical activity lost an average of 14.9% of their body weight over 68 weeks. Additionally, 69% of participants achieved at least 10% weight loss, a threshold associated with clinically meaningful health improvements.
Tirzepatide Weight Loss Results
The SURMOUNT trials demonstrated stronger outcomes. In the SURMOUNT-1 trial with 2,539 participants, patients taking 15 mg tirzepatide weekly (combined with diet and exercise) lost an average of 20.9% of their body weight over 72 weeks.
Head-to-Head Comparison
The most direct comparison came from the SURMOUNT-5 trial, which evaluated tirzepatide compared to semaglutide in adults with obesity. At 72 weeks, tirzepatide resulted in 20.2% average weight loss compared to 13.7% with semaglutide. When looking at weight loss thresholds, 78% of patients on tirzepatide achieved at least 15% weight loss, compared to 51% with semaglutide.
Real-World Evidence
A study published in JAMA Internal Medicine analyzed 18,386 adults who are overweight or with obesity in real-world clinical settings. At 12 months, tirzepatide users lost 15.3% of body weight compared to 8.3% with semaglutide.
Tirzepatide vs Semaglutide Dosage: How These Medications Are Prescribed
Both medications require gradual dose escalation (called titration) to minimize gastrointestinal side effects. This step-up approach, called titration, is essential for tolerability.
Semaglutide Dosing Schedule
With standard FDA-approved dosing, semaglutide starts at 0.25 mg once weekly for the first 4 weeks, then increases gradually every 4 weeks through a structured progression: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg. The maximum dose is typically reached around week 17-20. For detailed guidance, visit our semaglutide dosage chart.
Tirzepatide Dosing Schedule
Tirzepatide’s standard FDA-dosing begins at 2.5 mg once weekly for 4 weeks, then increases in 2.5 mg increments: 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg. The maximum dose is typically reached around week 21-24. See our tirzepatide dosage chart for full timing details.
While the milligram numbers look different, these doses aren’t directly comparable. Each medication has its own therapeutic range.
Tirzepatide vs Semaglutide Side Effects: What to Expect
Both medications affect the gastrointestinal system and appetite regulation, which means they share similar side effect profiles. Most side effects are mild to moderate, temporary, and improve as your body adjusts.
Common Side Effects of Tirzepatide and Semaglutide
The most frequently reported side effects include:
- Nausea (particularly during dose increases)
- Diarrhea or constipation
- Vomiting
- Abdominal discomfort
- Decreased appetite (expected effect)
Most side effects occur during dose escalation and typically improve within 4-8 weeks as your body adjusts to the medication. Many patients find that supportive strategies like proper hydration, gut health support, and working closely with their provider can help manage these effects effectively.
Switching from Semaglutide to Tirzepatide
Many patients successfully transition between these medications under proper medical supervision, whether moving from semaglutide to tirzepatide or tirzepatide to semaglutide.
When to Consider Switching From Semaglutide to Tirzepatide
You might benefit from transitioning if you’ve reached a weight loss plateau, are experiencing challenging side effects, have insurance coverage changes, or your provider recommends optimization based on your progress.
The Switching Protocol
If switching from semaglutide to tirzepatide:
- Take your last dose of semaglutide as scheduled
- Wait one week (your normal injection day)
- Start tirzepatide at the initial dose recommended by your provider
- Follow the prescribed titration schedule
Start tirzepatide at the dose recommended by your provider, even if you were on a higher dose of semaglutide. Yes, you’ve already been on a GLP-1 medication, but tirzepatide works on two receptors instead of one, so your body needs time to get used to it.
If switching from tirzepatide to semaglutide:
- Take your last dose of tirzepatide as scheduled
- Wait one week (your normal injection day)
- Start semaglutide at the initial dose recommended by your provider
- Follow the prescribed titration schedule
Even though you’re moving from a dual-agonist to a single GLP-1 agonist, your provider will still start you at the appropriate beginner dose to minimize side effects.
What to Expect During the Transition
You might notice some mild stomach side effects come back during the first few weeks, which is a normal part of adjusting to the new medication. Both medications stay in your system for several days, so you’ll maintain benefits and shouldn’t lose your progress during the transition.
Important: Never take tirzepatide and semaglutide together. It won’t give you better results and will only increase your risk of side effects.
Supporting Your Weight Loss Journey
While GLP-1 medications are powerful tools, supporting your muscle health during weight loss is essential. Research shows that adequate protein intake, amino acids and minerals, and resistance training can help preserve lean mass while losing fat.
Quality sleep also plays a crucial role in weight management and medication tolerability. Many patients find that addressing these foundational elements alongside their medication leads to better outcomes.
For men, understanding how GLP-1 medications interact with testosterone and muscle preservation can be particularly important. Women navigating menopause may benefit from combining GLP-1 therapy with hormone optimization for comprehensive metabolic support.
The Ivim Health Approach: GLP-1 ID for Individualized Results
Understanding the differences between tirzepatide and semaglutide is just the beginning. How these medications are prescribed, dosed, and supported can dramatically impact your outcomes.
Ivim Health’s GLP-1 ID program takes a different approach than traditional one-size-fits-all weight loss programs. Instead of standard dosing protocols, the GLP-1 ID model uses individualized virtual integrative medicine (IVIM) to personalize your treatment based on your unique response, tolerance, and goals.
What Makes GLP-1 ID Different
The semaglutide and tirzepatide used in this program are compounded medications*, custom formulations prepared by licensed compounding pharmacies. Compounding allows our providers to personalize dosing and tailor treatment for your specific needs and goals. Here’s what the GLP-1 ID program includes:
- Customized Dosing: Your medication dosing is tailored to your individual response, not just a standard dosing schedule. More frequent, slower dose increases allow for improved outcomes with lower risk of side effects.
- Comprehensive Support: Access to coaching, community support, and the iVIM Health app for ongoing guidance
- Formulated Supplements: Science-backed nutritional support designed specifically for GLP-1 therapy
- Data-Driven Adjustments: Regular monitoring and dose optimization based on your progress and tolerability
* The semaglutide and tirzepatide used in this program are compounded medications, custom formulations prepared by licensed compounding pharmacies. Compounding allows our providers to personalize dosing and tailor treatment for your specific needs and goals. Compounded medications may be prescribed only after a consultation with an IVIM Health provider and your provider will help you determine which drug is right for you. Compounded drugs are not FDA-approved and have not been reviewed by the FDA for safety, effectiveness, or quality. These products carry risks and are not appropriate for everyone.
Published Results
In a peer-reviewed study published in 2025, researchers analyzed 1,131 patients following the IVIM Protocol on semaglutide therapy. The results demonstrated significant weight loss outcomes: patients lost an average of 21.8% of their total body weight (46.9 lbs) at 68 weeks. At the 52-week mark, average weight loss was 19.5% of total body weight.
The study also found that 99.2% of patients achieved at least 5% weight loss, 93.9% lost 10% or more, and nearly half (47.8%) achieved 20% or more body weight loss. These outcomes highlight the effectiveness of personalized dosing, ongoing medical support, and comprehensive lifestyle coaching working together.
Whether you’re considering compounded semaglutide or compounded tirzepatide, the GLP-1 ID program provides the framework for maximizing your results while minimizing side effects through careful, personalized dosing and comprehensive support.
Tirzepatide vs Semaglutide Comparison Chart
*When combined with reduced-calorie diet and increased physical activity
Which Is Better: Tirzepatide or Semaglutide?
There’s no universal “best” medication. The right choice depends on your individual health history, goals, side effect tolerance, and practical considerations.
Tirzepatide may be appropriate if: You have tried semaglutide with good tolerance but want to see if tirzepatide would enhance your weight loss results, you have type 2 diabetes but have not had adequate glucose control on other GLP-1 medications, or have sleep apnea.
Semaglutide may be appropriate if: You have kidney disease, metabolic associated steatohepatitis (fatty liver) or cardiovascular disease.
Both may be contraindicated if you have: Personal or family history of medullary thyroid carcinoma, Multiple Endocrine Neoplasia syndrome type 2, history of severe pancreatitis, current pregnancy or plans to become pregnant, or severe kidney disease.
Get Started with Personalized Support at Ivim Health
If you’re ready to explore whether tirzepatide or semaglutide is right for your weight management journey, Ivim Health offers comprehensive telehealth support with board-certified providers who specialize in GLP-1 medications through our GLP-1 ID program.
Our Process
- Complete online assessment
- Virtual consultation with provider
- Individualized treatment plan with customized dosing
- Prescription & delivery directly to your door
- Ongoing support with coaching, community, and 24/7 messaging
Transparent Pricing
- Compounded Semaglutide Program: Starting at $150/month
- Compounded Tirzepatide: Starting at $224/month
Includes unlimited provider and coaching visits, medication and supplies, full app features for tracking and community support, live Q&As, and personalized dosing through our GLP-1 ID Program. Want to learn more about compounded medications and how they compare to brand-name options? Our team can walk you through your options during your free consultation.
Ready to start your weight loss journey with expert medical guidance and individualized support?
Reviewed by Emily Bigby, MD, Physician with Ivim Health
Medical Disclaimer:
This content is for informational and educational purposes only and is not intended as medical advice, diagnosis, or treatment. Always consult with a licensed healthcare provider before starting any new medication or treatment program.
Weight loss results may vary based on individual factors including starting weight, adherence to medication and lifestyle modifications, and underlying health conditions. The weight loss data presented represents average results from clinical trials when medications were combined with reduced calorie intake and increased physical activity.
Tirzepatide and semaglutide are prescription medications that require medical supervision. Compounded medications have not been approved by the FDA for safety, effectiveness, or quality and should only be used when FDA-approved medications are unavailable. Brand names mentioned are for informational purposes only. Ivim Health is not affiliated with any pharmaceutical manufacturers.
Sources:
Jensterle M, et al. Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Adv Ther. 2022;39(6):2452-2471. https://pmc.ncbi.nlm.nih.gov/articles/PMC9063254/
Kumar D, et al. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Cureus. 2022;14(1):e21340. https://pmc.ncbi.nlm.nih.gov/articles/PMC8736331/
Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2416394
Rodriguez PJ, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. 2024;184(9):1056-1064. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2821080
Kantor T, et al. Individualized virtual integrative medicine (IVIM): A clinical model for enhanced GLP-1 therapeutic outcomes. PMC. 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12272120/
