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
Semaglutide
Tirzepatide
Drug class
GLP-1 agonist
Dual GIP + GLP-1 agonist
Brands
Wegovy, Ozempic
Zepbound, Mounjaro
Avg. weight loss
~14.9% (STEP 1)
~20.9% at 15 mg (SURMOUNT-1)
Head-to-head
Tirzepatide ~20.2% vs semaglutide ~13.7% (SURMOUNT-5)
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.
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.
SURMOUNT-5 found tirzepatide produced roughly 50% more relative weight loss — but semaglutide still delivered substantial, clinically meaningful results.
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.
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.
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).
Many do, starting tirzepatide low rather than dose-matching, under clinical supervision.
Clinical references
Wilding JPH, et al. STEP 1. N Engl J Med. 2021;384(11):989–1002.
Jastreboff AM, et al. SURMOUNT-1. N Engl J Med. 2022;387(3):205–216.
Aronne LJ, et al. Tirzepatide vs Semaglutide (SURMOUNT-5). N Engl J Med. 2025.
Frías JP, et al. SURPASS-2. N Engl J Med. 2021;385(6):503–515.
Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes (SELECT). N Engl J Med. 2023;389(24):2221–2232.
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.