Semaglutide vs. Tirzepatide: A Detailed Comparison

The two leading GLP-1 weight-loss medications, compared on the evidence.

✓ Medically reviewedUpdated 2026

The bottom line

Tirzepatide produces more weight loss on average — about 20% vs semaglutide’s 14% in the SURMOUNT-5 head-to-head. Both are highly effective once-weekly injections with similar, manageable GI side effects. Semaglutide has the longer track record and dedicated cardiovascular data; tirzepatide is the newer, more potent dual-agonist. The right choice comes down to tolerability, history, cost and clinician judgment.

At a glance

 SemaglutideTirzepatide
Drug classGLP-1 agonistDual GIP + GLP-1 agonist
BrandsWegovy, OzempicZepbound, Mounjaro
Avg. weight loss~14.9% (STEP 1)~20.9% at 15 mg (SURMOUNT-1)
Head-to-headTirzepatide ~20.2% vs semaglutide ~13.7% (SURMOUNT-5)
Top dose2.4 mg15 mg
Compounded from$199/mo$129/mo

How they work

Semaglutide activates one receptor (GLP-1); tirzepatide activates two (GIP + GLP-1). Both are once-weekly injections that curb appetite and slow gastric emptying; the second pathway is thought to drive tirzepatide's larger average effect.

Weight loss: the evidence

Average weight loss in pivotal obesity trials (68–72 weeks)
STEP 1 (semaglutide 2.4 mg) and SURMOUNT-1 (tirzepatide). Different trials — not head-to-head.
Semaglutide 2.4 mgSemaglutide 2.4 mg: 14.9%14.9% STEP 1Tirzepatide 5 mgTirzepatide 5 mg: 15.0%15.0% SURMOUNT-1Tirzepatide 10 mgTirzepatide 10 mg: 19.5%19.5%Tirzepatide 15 mgTirzepatide 15 mg: 20.9%20.9%

Those are different trials. The fairest read is the direct comparison, SURMOUNT-5:

Head-to-head: SURMOUNT-5 (72 weeks)
Aronne LJ et al., NEJM 2025 — first direct obesity trial.
TirzepatideTirzepatide: 20.2%20.2% top doseSemaglutideSemaglutide: 13.7%13.7% 2.4 mg
SURMOUNT-5 found tirzepatide produced roughly 50% more relative weight loss — but semaglutide still delivered substantial, clinically meaningful results.

Dosing

Typical once-weekly dose escalation
Wegovy (semaglutide) & Zepbound (tirzepatide) labeling.
Semaglutide0.250.51.01.72.4 mgTirzepatide2.557.51012.515 mg
Each step is typically maintained ~4 weeks before increasing, as tolerated. Your clinician sets and adjusts your schedule.

Side effects

Similar and mostly gastrointestinal — nausea, diarrhea, constipation, vomiting — usually mild-to-moderate, dose-dependent, and eased by slow titration. Both carry a thyroid C-cell tumor boxed warning.

Cost

Typical monthly cost (cash, before insurance)
Brand list prices approximate; compounded = DripVitals start rate. Compounded is not FDA-approved.
Brand (Wegovy/Zepbound)Brand (Wegovy/Zepbound): $1,349$1,349 listCompounded semaglutideCompounded semaglutide: $199$199 DripVitalsCompounded tirzepatideCompounded tirzepatide: $129$129 DripVitals

Which is right for you?

Semaglutide may fit if you…

  • Want the longest real-world track record
  • Value its cardiovascular-outcomes data (SELECT)
  • Prefer a simpler titration

Tirzepatide may fit if you…

  • Want the largest average weight loss in trials
  • Haven't reached your goal on a GLP-1 alone
  • Want the lower starting price

Getting treatment online

DripVitals is an online clinic: complete a secure intake, a licensed clinician reviews it, and if a GLP-1 medication is appropriate it ships from a licensed pharmacy to your door, with follow-ups by message or video.

See if you qualifyExplore GLP-1 treatments

Related comparisons

Wegovy vs. ZepboundOzempic vs. WegovyMounjaro vs. ZepboundCompounded vs. brand-name

Frequently asked questions

Is tirzepatide better than semaglutide?

In SURMOUNT-5 tirzepatide produced greater average weight loss (~20% vs ~14%). But the best option depends on tolerability, history, cost and goals — many people do very well on semaglutide.

What's the core difference?

Semaglutide acts on one receptor (GLP-1); tirzepatide acts on two (GIP + GLP-1).

Are Ozempic and Mounjaro the same thing?

Ozempic/Wegovy are semaglutide; Mounjaro/Zepbound are tirzepatide. See Ozempic vs Wegovy and Mounjaro vs Zepbound.

Can I switch from semaglutide to tirzepatide?

Many do, starting tirzepatide low rather than dose-matching, under clinical supervision.

Clinical references

  1. Wilding JPH, et al. STEP 1. N Engl J Med. 2021;384(11):989–1002.
  2. Jastreboff AM, et al. SURMOUNT-1. N Engl J Med. 2022;387(3):205–216.
  3. Aronne LJ, et al. Tirzepatide vs Semaglutide (SURMOUNT-5). N Engl J Med. 2025.
  4. Frías JP, et al. SURPASS-2. N Engl J Med. 2021;385(6):503–515.
  5. Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes (SELECT). N Engl J Med. 2023;389(24):2221–2232.
  6. FDA prescribing information: Wegovy; Zepbound.
Medically reviewed. For general education only — not medical advice, and not a substitute for a consultation with a licensed clinician. Trial figures are group averages; individual results vary. Compounded medications are not FDA-approved.
GLP-1 medications are prescription treatments with risks and contraindications, including a boxed warning for thyroid C-cell tumors; do not use with a personal or family history of medullary thyroid carcinoma or MEN 2. This page is not medical advice; a licensed clinician determines whether treatment is appropriate for you.