Using the shot

Tirzepatide or semaglutide?

One produced larger average weight loss in a head-to-head trial. The other is gentler on the wallet and, for some people, on the stomach.

Illustration of an open book with a path drawn across it

Updated 2026-09-18


Both are weekly injections. Both reduce appetite. They are not the same drug, and there is a trial that compared them directly.

SURMOUNT-5 compared the two drugs directly. Participants on tirzepatide lost an average of 50.3 lb (22.8 kg); those on semaglutide lost 33.1 lb (15.0 kg). That is a substantial difference, and it is the main reason tirzepatide costs more nearly everywhere you look.

How they differ

Tirzepatide — A single weekly injection that activates two gut hormone receptors, GIP and GLP-1, rather than one. Sold as Zepbound and Mounjaro. In SURMOUNT-1, adults with obesity lost an average of 19.5% of body weight on 10 mg and 20.9% on 15 mg over 72 weeks.

Semaglutide — A weekly injection that activates the GLP-1 receptor, slowing stomach emptying and reducing appetite signalling. Sold as Wegovy and Ozempic. In STEP-1, adults on 2.4 mg lost an average of about 14.9% of body weight over 68 weeks.

Reasons people choose semaglutide anyway

  • It costs less almost everywhere — roughly $149 to $298 a month against $199 to $449 for tirzepatide.
  • It has been in wide use longer, so there is more accumulated real-world experience.
  • Some people tolerate it better, though both carry the same broad side-effect profile.
  • Insurance is somewhat more likely to have a pathway for branded semaglutide.

The dose ladders side by side

TirzepatideSemaglutide
Doses2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg
Step up every~4 weeks~4 weeks
Cheapest all-in$199/mo$149/mo
Typical all-in$278–$449/mo$178–$297/mo

Full tables in the cheapest weekly shots.

Side effects

Tirzepatide: Nausea, diarrhoea, constipation and reflux, concentrated in the weeks after each dose increase.

Semaglutide: Nausea, vomiting, diarrhoea and constipation, usually worst in the first weeks and after dose increases.

For both, the pattern follows the dose increases — see side effects week by week.

So which?

If budget is the constraint, semaglutide is the sensible starting point and still produced about 15% average weight loss in its trials. If you can afford the difference and want the larger average result, tirzepatide. Either way it is a decision for the clinician who will be prescribing — both have contraindications, and neither is right for everyone.

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