How semaglutide works
Semaglutide is a GLP-1 receptor agonist. GLP-1 (glucagon-like peptide-1) is a hormone released naturally after eating that signals fullness to the brain and slows gastric emptying. Semaglutide mimics this effect, reducing appetite and caloric intake over time.
It was originally developed for type 2 diabetes management and later approved by the FDA for chronic weight management in adults with obesity or overweight with at least one weight-related condition.
Key FDA approvals:
- Ozempic (semaglutide 0.5mg-2mg weekly injection) - approved for type 2 diabetes
- Wegovy (semaglutide up to 2.4mg weekly injection) - approved for chronic weight management
- Rybelsus (oral semaglutide) - approved for type 2 diabetes
How tirzepatide works
Tirzepatide is a dual agonist - it activates both GLP-1 receptors and GIP (glucose-dependent insulinotropic polypeptide) receptors. GIP is another gut hormone that plays a role in insulin secretion and fat storage.
The dual mechanism appears to produce somewhat greater weight loss on average compared to semaglutide in clinical trials, though individual responses vary considerably.
Key FDA approvals:
- Mounjaro (tirzepatide weekly injection) - approved for type 2 diabetes
- Zepbound (tirzepatide weekly injection) - approved for chronic weight management
What clinical trials showed
Clinical trials for both medications showed meaningful weight loss in the right patient populations:
- Semaglutide (Wegovy dose): average weight loss of around 15-17% of body weight over 68 weeks in the STEP trials
- Tirzepatide (Zepbound dose): average weight loss of 20-22% of body weight over 72 weeks in the SURMOUNT trials
These are averages from trial populations. Individual results vary based on starting weight, adherence, diet, exercise, and other factors. Neither medication is a replacement for lifestyle changes, and both require ongoing use to maintain results - weight typically returns when the medication is stopped.
Compounded versions: what they are and why they exist
Brand-name semaglutide and tirzepatide are expensive without insurance, often $900-1,400 per month. Because of this, and because both drugs experienced periods of FDA-designated shortage, compounding pharmacies began producing lower-cost versions using the same active pharmaceutical ingredients.
Compounded semaglutide and tirzepatide are:
- Not FDA-approved (the compound itself is not evaluated by the FDA)
- Legally produced under 503A (patient-specific) or 503B (larger scale) pharmacy standards when a valid shortage designation applies
- Often significantly cheaper - many programs offer compounded versions for $150-400/month
- Widely available through telehealth clinics
The FDA has issued warnings about some compounded formulations, particularly regarding salt forms (like semaglutide sodium vs. semaglutide free acid base) and inaccurate dosing. When evaluating any compounded program, it matters which pharmacy produces the medication and what their quality standards are.
Cost comparison
The actual cost you pay depends on several factors:
| Option | Approx monthly cost |
|---|---|
| Brand-name Wegovy (with insurance) | $0-200 (if covered) |
| Brand-name Wegovy (without insurance) | $1,000-1,400 |
| Brand-name Zepbound (without insurance) | $1,000-1,400 |
| Compounded semaglutide via telehealth | $150-400 |
| Compounded tirzepatide via telehealth | $200-500 |
Insurance coverage for weight management medications is inconsistent - many plans exclude them entirely, including Medicare until 2026 changes begin to phase in coverage for some patients.
Questions to ask your doctor
When speaking with a physician about either medication, these are worth raising:
- Which medication makes more clinical sense for my situation, and why?
- Should I start with semaglutide or tirzepatide given my health history?
- Am I a candidate for the branded version, or would a compounded version be appropriate?
- If compounded, which pharmacy do you use and how do you verify quality?
- What dose will I start at, and how will it be titrated?
- What side effects should I expect, and what would cause you to stop or pause the medication?
- What lab monitoring do you recommend while I am on this?
- What happens if I need to stop - is there a tapering protocol?
Which one should you choose?
That is a question for your physician, not a comparison article. Both medications are FDA-approved and have real clinical evidence behind them. The right choice depends on your medical history, any existing conditions (particularly diabetes or cardiovascular history), your response to treatment, and cost and access factors specific to your situation.
What matters before you get to that conversation is finding a clinic with a physician who will actually review your history, discuss the options properly, and monitor your progress over time. Browse physician-supervised clinics to compare options near you.