Semaglutide vs Tirzepatide
This is the central question in GLP-1 treatment. Semaglutide (Wegovy/Ozempic) targets one gut-hormone receptor; tirzepatide (Zepbound/Mounjaro) targets two. In head-to-head data, tirzepatide produces more weight loss on average — but semaglutide has the longer track record and landmark cardiovascular-outcome evidence. Here's how to choose.
Last reviewed 2026-09-01 by the TopGLP1 Editorial Team
Educational, not medical advice. This page explains GLP-1 medications in general terms. Only a licensed clinician who knows your history can decide what's right for you.
For maximum average weight loss, tirzepatide is the stronger choice — a head-to-head trial (SURMOUNT-5) confirmed it beats semaglutide. Choose semaglutide if you value the longer track record and proven cardiovascular benefit.
Choose Semaglutide if…
you want the longest track record and proven cardiovascular-event reduction (SELECT).
Choose Tirzepatide if…
you want the highest average weight loss and didn't reach your goal on semaglutide.
Side by side
| Semaglutide | Tirzepatide | |
|---|---|---|
| Drug class | GLP-1 receptor agonist | Dual GIP/GLP-1 receptor agonist |
| Brand names | Wegovy, Ozempic, Rybelsus | Zepbound, Mounjaro |
| Route | Weekly injection (or daily oral) | Weekly injection |
| Avg. weight loss | ~15% (STEP 1, 68 wks) | ~15–21% (SURMOUNT-1, 72 wks) |
| Head-to-head | Less weight loss in SURMOUNT-5 | Superior weight loss in SURMOUNT-5 |
| Cardiovascular data | 20% MACE reduction (SELECT) | Strong metabolic data; CV outcomes maturing |
| Approval | FDA-approved | FDA-approved |
How they compare on results
In their pivotal trials, semaglutide 2.4 mg produced about 15% average weight loss over 68 weeks (STEP 1), while tirzepatide reached roughly 15%, 19% and up to ~21% across its 5, 10 and 15 mg doses over 72 weeks (SURMOUNT-1). A direct head-to-head trial, SURMOUNT-5, found tirzepatide produced greater average weight loss than semaglutide.
So on the single question of 'which takes off more weight on average,' tirzepatide wins. But semaglutide's SELECT trial showed a 20% reduction in major cardiovascular events in adults with obesity and existing heart disease — the kind of hard-outcome evidence tirzepatide is still accumulating. If cardiovascular protection is your priority, that tilts things back toward semaglutide.
Side effects & safety
Side-effect profiles are very similar — mostly gastrointestinal (nausea, constipation, diarrhea), worst during dose escalation, plus the same class warnings (pancreatitis, gallbladder, thyroid C-cell boxed warning). Neither is safe with a personal/family history of medullary thyroid carcinoma or MEN 2.
Cost
Branded, both list around $1,000+/month cash. Compounded versions are far cheaper — our top pick Embody offers compounded semaglutide at $69/mo and tirzepatide at $119/mo, flat.
Full drug guides
Semaglutide vs Tirzepatide: common questions
Sources & references
Clinical figures on this page trace to peer-reviewed trials and official regulators. We link the primary record so you can verify it yourself.
- 1.Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002.Clinical trialNew England Journal of Medicine
- 2.Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216.Clinical trialNew England Journal of Medicine
- 3.Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025.Clinical trialNew England Journal of Medicine
- 4.Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221–2232.Clinical trialNew England Journal of Medicine