Semaglutide vs Tirzepatide: Which GLP-1 Should You Start On?

Semaglutide is a GLP-1 receptor agonist: it copies a gut hormone that slows stomach emptying, increases fullness and lowers appetite. It is sold as Wegovy (approved for chronic weight management) and Ozempic (approved for type 2 diabetes).

Tirzepatide activates both the GLP-1 receptor and the GIP receptor, a second appetite- and metabolism-related hormone pathway. It is sold as Zepbound (approved for chronic weight management) and Mounjaro (type 2 diabetes). Both are usually taken as a weekly injection, starting at a low dose that a clinician steps up over several months.

On average, tirzepatide. The key trial numbers:

• STEP-1 (semaglutide 2.4 mg): about 15% average body-weight loss at 68 weeks.
• SURMOUNT-1 (tirzepatide 15 mg): about 21% at 72 weeks.
• SURMOUNT-5, the direct head-to-head published in NEJM in 2025: tirzepatide about 20.2% vs semaglutide about 13.7% at 72 weeks.

Those are trial averages with brand-name medication, diet and activity support. Individual results vary widely - some people do very well on semaglutide, and some respond less than average to either. Compounded versions were not the products tested in these trials.

The side-effect profiles are similar: nausea, vomiting, diarrhea, constipation, reflux, fatigue and reduced appetite, usually worst in the days after a dose increase. Both carry the same boxed warning about thyroid C-cell tumors seen in rodents, and neither is used by people with a personal or family history of medullary thyroid carcinoma or MEN2, or during pregnancy.

There is no reliable way to predict in advance which one you will tolerate better. If one drug causes persistent side effects, a clinician may slow the titration, hold your dose or switch you to the other. Our guide to side effects in the first 12 weeks covers what to expect.

Tirzepatide costs more almost everywhere. Compounded prices on our list:

• embody: semaglutide $69/mo, tirzepatide $119/mo (month-to-month)
• wellmedr: semaglutide $49/mo on a 12-month plan, tirzepatide $89/mo
• altRx: semaglutide $89/mo, tirzepatide $149/mo (promo rates; regular $199 and $299)
• trimrx: semaglutide $149/mo, tirzepatide $259/mo
• MEDVi: semaglutide $99/mo, tirzepatide $166/mo (promo rates; regular $199 and $299)

On brand-name self-pay, Zepbound is listed at $1,249-$1,599/mo and Wegovy at $1,579/mo on the platforms we track. With insurance, the picture depends entirely on your plan - ro can check coverage for both. Full breakdown: the real cost of GLP-1 weight loss.

• If maximum average weight loss is your priority and the higher price fits your budget, tirzepatide has the stronger head-to-head data.
• If cost is the deciding factor, semaglutide is typically $40-$110 a month cheaper compounded and still produced about 15% average loss in STEP-1.
• If your insurance covers only one, start with the covered one - the savings usually outweigh the difference in averages.
• If you would prefer a pill to a weekly injection, ask about oral options: ro offers brand-name oral medication, and embody offers a daily oral compounded option.
• If you have tried one and stalled or could not tolerate it, ask your clinician whether switching makes sense.

A licensed clinician makes the final call based on your history, other medications and goals. Compare providers side by side in our GLP-1 provider rankings.

This article is general information, not medical advice. A licensed clinician should decide what treatment, if any, is right for you. Results vary.