GLP-1 comparison
Tirzepatide vs Semaglutide
The two heavyweights of weight loss. Tirzepatide (Zepbound, Mounjaro) hits two hormone targets and wins on average weight loss; semaglutide (Wegovy, Ozempic) has the longer track record and a pill option. Here's how they really stack up.
Tirzepatide
The efficacy leader
Dual GIP + GLP-1 action and the largest average weight loss of any approved obesity drug — up to ~21% at 15 mg. Injection only.
Semaglutide
The proven standard
Powerful ~15% average loss, a longer real-world track record, and the only one with an oral pill option (Rybelsus).
Side by side
Tirzepatide
Zepbound / Mounjaro
Semaglutide
Wegovy / Ozempic
Highlighted cells indicate the stronger option for that row. The efficacy figures above come from each drug's own pivotal trial and are not a head-to-head comparison — those trials enrolled different patients under different designs. For direct evidence, see SURMOUNT-5 below.
What do head-to-head studies show?
The pivotal trials in the table above shouldn't be compared directly: STEP 1 and SURMOUNT-1 enrolled different patients, ran for different lengths, and used different study designs. A cross-trial comparison can only hint at a difference — it can't prove one.
SURMOUNT-5 settles that by putting the two drugs in the same randomized trial. It compared tirzepatide and semaglutide, each titrated to its maximum tolerated dose, in adults with obesity but without diabetes over 72 weeks — the first large head-to-head between them.
Tirzepatide
≈ 20%
average body-weight loss at 72 weeks
Semaglutide
≈ 14%
average body-weight loss at 72 weeks
In plain terms: in this one trial, tirzepatide produced meaningfully greater average weight loss than semaglutide, and more participants reached the larger weight-loss milestones. Both drugs still produced substantial loss, and the side-effect profiles were broadly similar.
See your numbers on each
Enter your weight and compare projected loss on tirzepatide vs semaglutide, using the real SURMOUNT-1 and STEP 1 trial averages.
Which one is right for you?
You want maximum average weight loss
Tirzepatide has the edge on the numbers, thanks to its dual GIP/GLP-1 mechanism and higher ceiling of loss.
You'd prefer a pill, or a longer track record
Semaglutide is the only one with an oral option (Rybelsus) and has been in wide use longer, which some people and prescribers prefer.
Access and cost are the deciding factor
For most people it comes down to what their insurance covers and what they can tolerate. The best drug is the one you can actually stay on.
Either way — protect your muscle
Whichever you choose, up to 40% of the weight lost can be muscle without enough protein and resistance training. That's the real make-or-break for keeping it off.
Frequently Asked Questions
Sources
Evidence hierarchy: FDA prescribing information, pivotal clinical trials, and the SURMOUNT-5 head-to-head trial for direct comparison.
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)Aronne LJ, Horn DB, le Roux CW, et al. N Engl J Med. 2025;393:26–36. doi:10.1056/NEJMoa2416394
- Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)Wilding JPH, Batterham RL, Calanna S, et al. N Engl J Med. 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183
- Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)Jastreboff AM, Aronne LJ, Ahmad NN, et al. N Engl J Med. 2022;387(3):205–216. doi:10.1056/NEJMoa2206038
- Wegovy (semaglutide) Prescribing InformationU.S. Food & Drug Administration (FDA). 2023.
- Zepbound (tirzepatide) Prescribing InformationU.S. Food & Drug Administration (FDA). 2023.
Tool Information
July 24, 2026
Dr. Jaydeep Sanghani
Meet Akabari
Dr. Jaydeep Sanghani
MBBS, MD, DNB(Anaesth.), PDCC(CCM), DrNB(CCM)
AIIMS Bhubaneswar · AIIMS Rishikesh
Critical care specialist and anesthesiologist with advanced training from AIIMS. Reviews health calculators at Calqulate to ensure medical accuracy and evidence-based standards.