Quick Answer
Both semaglutide (Wegovy) and tirzepatide (Zepbound) are effective weekly GLP-1 injections for weight loss, but they work differently. Tirzepatide targets two hormone receptors (GIP and GLP-1) while semaglutide targets one (GLP-1 only). In a head-to-head clinical trial (SURMOUNT-5), tirzepatide produced greater average weight loss — approximately 20.2% of body weight compared to 13.7% with semaglutide over 72 weeks. However, the right choice depends on your medical history, tolerability, insurance coverage, cost, and your licensed provider's clinical judgment.
Semaglutide vs Tirzepatide: Comparison at a Glance
The table below summarizes the key differences between semaglutide and tirzepatide for weight loss based on FDA-approved prescribing information, published clinical trials, and publicly available cost data.
| Feature | Semaglutide (Wegovy) | Tirzepatide (Zepbound) |
|---|---|---|
| Drug class | GLP-1 receptor agonist | Dual GIP/GLP-1 receptor agonist |
| Brand names (FDA-approved) | Wegovy (weight loss), Ozempic (type 2 diabetes) | Zepbound (weight loss), Mounjaro (type 2 diabetes) |
| Dosing frequency | Once weekly (subcutaneous injection) | Once weekly (subcutaneous injection) |
| Starting dose | 0.25 mg weekly | 2.5 mg weekly |
| Maintenance dose range | 1.7–2.4 mg weekly | 5–15 mg weekly |
| Average weight loss (clinical trials) | ~15% of body weight (STEP 1 trial, 68 weeks) | ~21% of body weight (SURMOUNT-1, 72 weeks) |
| Most common side effects | Nausea, diarrhea, vomiting, constipation, abdominal pain | Nausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite |
| Head-to-head result (SURMOUNT-5) | 13.7% mean weight loss at 72 weeks | 20.2% mean weight loss at 72 weeks |
Sources: Zepbound prescribing information (FDA, 2023); Wegovy prescribing information (FDA, 2021); SURMOUNT-1 (NEJM, 2022); STEP 1 (NEJM, 2021); SURMOUNT-5 (JAMA Internal Medicine, 2025). Compounded preparations are not included in this comparison.
How Each Medication Works
Semaglutide acts on a single hormone pathway. Tirzepatide acts on two. This mechanistic difference appears to explain some of the additional weight loss seen in clinical trials.
Semaglutide: GLP-1 Receptor Agonist
Mimics the glucagon-like peptide-1 (GLP-1) hormone, which signals the brain to reduce appetite, slows stomach emptying, and increases insulin release when blood sugar is high. It acts on a single receptor type.
Tirzepatide: Dual GIP/GLP-1 Receptor Agonist
Mimics both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). This dual action may enhance appetite suppression, increase energy expenditure, and improve how the body processes fat — effects that appear to produce greater weight reduction than GLP-1 agonism alone.
Source: Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. NEJM. 2022. PubMed
Which Produced Greater Average Weight Loss in Head-to-Head Research?
Tirzepatide produced greater mean weight loss than semaglutide in the only published head-to-head trial of FDA-approved formulations for weight loss — SURMOUNT-5.
SURMOUNT-5 directly compared tirzepatide (Zepbound) with semaglutide (Wegovy) in adults with obesity or overweight with at least one weight-related condition, without type 2 diabetes. The trial lasted 72 weeks.
SURMOUNT-5 Results at 72 Weeks
Semaglutide (Wegovy)
13.7%
mean weight loss
Tirzepatide (Zepbound)
20.2%
mean weight loss
For a person weighing 220 pounds, a 13.7% reduction would mean losing approximately 30 pounds, while a 20.2% reduction would translate to roughly 44 pounds — a difference of about 14 pounds between the two medications on average. These are averages; individual results vary.
Source: Trico D, et al. Tirzepatide vs Semaglutide for Weight Loss — SURMOUNT-5. JAMA Internal Medicine. 2025. PubMed. Individual results vary. These results reflect branded FDA-approved medications in a controlled clinical trial and do not guarantee results from compounded formulations.
How Quickly Results May Appear
Weight loss typically begins within the first month, becomes more noticeable after 8–12 weeks, and tends to be most pronounced once the maintenance dose is reached.
In clinical trials, both semaglutide and tirzepatide showed measurable weight reduction within the first 4 weeks. However, the rate of loss and total reduction differed. Tirzepatide's dual mechanism may produce faster initial weight loss for some patients, but quicker onset does not guarantee a better long-term result.
The licensed provider determines the titration schedule — how quickly the dose increases — based on your individual response and any side effects you experience. Going faster is not always better or safer.
Side-Effect Comparison
Both medications share similar gastrointestinal side effects. The severity and duration vary by individual.
| Side Effect | Semaglutide | Tirzepatide |
|---|---|---|
| Nausea | Very common (44%) | Very common (29–33%) |
| Diarrhea | Common (30%) | Common (21–23%) |
| Vomiting | Common (24%) | Common (9–13%) |
| Constipation | Common (24%) | Common (12–16%) |
| Abdominal pain | Common (20%) | Common (9–13%) |
| Decreased appetite | Common (9%) | Common (12–15%) |
| Injection-site reaction | Uncommon | Uncommon (3–4%) |
Percentages reflect rates reported in clinical trials. Individual experiences vary. Most gastrointestinal side effects are mild to moderate and tend to decrease over time. Sources: Wegovy PI (FDA); Zepbound PI (FDA); SURMOUNT-1 (NEJM, 2022); STEP 1 (NEJM, 2021).
Dose and Titration Comparison
Both medications follow a gradual dose-escalation schedule designed to help your body adjust and minimize side effects. Neither medication starts at the full therapeutic dose.
Semaglutide Titration
Tirzepatide Titration
Note: The licensed provider determines the actual titration pace and final maintenance dose. Not all patients reach the maximum dose. Compounded prescriptions follow the licensed provider's clinical judgment, not the branded titration schedule above.
Cost and Insurance Considerations
Cost varies dramatically depending on whether you use an FDA-approved branded medication through insurance, a branded medication paid out of pocket, or a compounded formulation through a telehealth provider.
Cost Comparison Overview
Branded, with insurance
Copays vary widely ($25–$200+/month). Prior authorization is often required. Coverage depends on the specific plan's formulary.
Branded, without insurance (cash price)
List prices exceed $1,000/month for both Wegovy and Zepbound. Manufacturer savings programs may reduce the cost for eligible patients.
Compounded, through a telehealth provider
Typically $200–$500/month including provider review, medication, supplies, and shipping. Open Water Rx offers semaglutide at $169/mo and tirzepatide at $219/mo — an all-inclusive monthly price within the selected treatment plan.
Open Water Rx pricing as of publication date. Prices are subject to change. View current pricing.
For more on what tirzepatide programs charge, see this breakdown of tirzepatide cost.
FDA-Approved Versus Compounded Formulations
There is an important regulatory distinction between FDA-approved branded medications and compounded preparations.
FDA-Approved (Branded)
- Reviewed by the FDA for safety and efficacy
- Manufactured under strict quality standards
- Delivered in a branded autoinjector pen
- Usually more expensive; may be covered by insurance
Compounded
- Not reviewed by the FDA for safety, efficacy, or quality
- Prepared by state-licensed compounding pharmacies
- Delivered in vials with syringes (not autoinjector pens)
- Usually less expensive; generally not covered by insurance
Compounded medications are not generic versions of branded medications and are not FDA-approved. They are prescribed based on a licensed provider's clinical judgment. FDA: Compounding Q&A
Which Option May Suit Different Patient Priorities?
There is no single "better" medication for everyone. The right choice depends on your specific priorities, medical history, and your licensed provider's recommendation.
Greatest potential weight loss, based on clinical trial data
Tirzepatide showed greater mean weight loss in head-to-head research. However, individual response varies — some patients lose more weight on semaglutide.
Lower medication cost
Compounded semaglutide is often priced lower than compounded tirzepatide. Check current pricing and included services from each provider.
Minimizing side effects
Side-effect rates differ slightly between the two. Semaglutide was associated with higher rates of nausea and vomiting in SURMOUNT-5, while tirzepatide had higher rates of decreased appetite. Your provider can adjust the titration pace to improve tolerability for either medication.
Insurance coverage
Check your plan's formulary for Wegovy and Zepbound coverage. If neither is covered, a compounded option through a telehealth provider may be more affordable than the branded cash price.
Longest available clinical data
Semaglutide has a longer history of use for weight management (FDA-approved in 2021). Tirzepatide was approved for weight loss more recently (2023). Both have extensive safety data from large clinical trial programs.
Questions to Ask a Licensed Provider
Before starting either medication, consider asking your provider these questions.
- Based on my medical history, is semaglutide or tirzepatide more appropriate for me?
- What dose would I start on, and how quickly would it increase?
- What side effects should I watch for, and how can I manage them?
- How often will we check in to monitor my progress?
- Is this a branded or compounded formulation? If compounded, which pharmacy prepares it?
- What am I paying for — just the medication, or does the price include provider visits, supplies, and shipping?
- If my insurance doesn't cover this, what are my options?
Key Takeaways
- Tirzepatide targets both GIP and GLP-1 receptors; semaglutide targets GLP-1 only.
- In the SURMOUNT-5 head-to-head trial, tirzepatide produced greater mean weight loss (20.2% vs 13.7% at 72 weeks).
- Both medications share similar gastrointestinal side effects, though rates differ slightly.
- Dose titration schedules are different — tirzepatide has more dose steps than semaglutide.
- Compounded formulations are not equivalent to branded medications.
- Cost varies considerably depending on insurance coverage, branded vs compounded route, and provider pricing model.
- The right choice depends on your medical history, priorities, tolerability, and your licensed provider's clinical judgment.
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Check My EligibilityReferences
- U.S. Food and Drug Administration. Zepbound (tirzepatide) prescribing information. accessdata.fda.gov
- U.S. Food and Drug Administration. Wegovy (semaglutide) prescribing information. accessdata.fda.gov
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387:205-216. PubMed
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021;384:989-1002. PubMed
- Trico D, et al. Tirzepatide vs Semaglutide for Weight Loss — SURMOUNT-5. JAMA Internal Medicine. 2025. PubMed
- National Institutes of Health. Prescription Medications to Treat Overweight & Obesity. niddk.nih.gov
- U.S. Food and Drug Administration. Compounding and FDA: Questions and Answers. fda.gov