Two drugs dominate the GLP-1 weight loss conversation right now: semaglutide (sold as Ozempic for diabetes and Wegovy for obesity) and tirzepatide (Mounjaro for diabetes, Zepbound for obesity). Both work. Both produce meaningful weight loss. But they are not identical — and the difference matters when you're comparing clinics and trying to figure out which one your insurance will actually cover.
How They Work
Semaglutide is a GLP-1 receptor agonist. It mimics a gut hormone that signals fullness to your brain, slows stomach emptying, and reduces appetite. It's a once-weekly injectable.
Tirzepatide is a dual GIP/GLP-1 receptor agonist — it hits both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. The second target appears to amplify the weight loss effect, which is why clinical trials show slightly higher average weight loss with tirzepatide.
Weight Loss: What the Trials Show
In clinical trials at the highest doses:
- Semaglutide (Wegovy 2.4mg): Average 14–16% body weight reduction over 68 weeks (STEP 1 trial)
- Tirzepatide (Zepbound 15mg): Average 20–22% body weight reduction over 72 weeks (SURMOUNT-1 trial)
A 6–8% difference sounds modest in a trial setting, but at 250 lbs that's 15–20 additional pounds lost. Individual results vary substantially — some patients lose 30%+ on semaglutide while others lose less than 10% on tirzepatide.
Side Effects
Both drugs share the same primary side effect profile: nausea, constipation, diarrhea, and occasionally vomiting — especially in the first several weeks as your dose increases. For most people these fade after the first 1–2 months.
The side effects aren't meaningfully different between the two drugs. Some patients who had significant nausea on semaglutide tolerate tirzepatide better, and vice versa. There's no reliable way to predict this in advance.
Cost and Insurance
This is where the real difference shows up day-to-day:
- Brand-name Wegovy: $1,100–$1,350/month without insurance. Many major commercial insurers now cover it for obesity. Manufacturer savings cards can bring cost to $0–$25/month for commercially insured patients.
- Brand-name Zepbound: $1,000–$1,100/month without insurance. Coverage is growing but narrower than Wegovy. Eli Lilly savings card available for commercially insured patients.
- Compounded semaglutide: $150–$350/month. Widely available from licensed 503B compounding pharmacies through telehealth and clinic programs. FDA-approved shortage status determines availability.
- Compounded tirzepatide: $200–$450/month. Available through similar channels, though Eli Lilly has been more aggressive about restricting compounding.
Which One Should You Try First?
The answer is usually: whichever your insurance covers, or whichever your clinic's physician recommends based on your medical history. There's no universally "better" drug — only the one that works best for you individually.
If you have type 2 diabetes, semaglutide (Ozempic) has the longest track record and broadest insurance formulary coverage for the diabetes indication. If you're treating obesity without diabetes, the coverage picture is more complex — ask a clinic to run your benefits before your first appointment.
If cost is the primary concern, compounded semaglutide through a telehealth provider is typically the most accessible entry point.