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Guide · updated 2026-08-24

Semaglutide vs tirzepatide, on the evidence

Last verified 2026-08-24 · methodology · conflict-of-interest disclosure · dataset: open JSON

Mechanism: semaglutide is a GLP-1 agonist; tirzepatide adds GIP — and in the approved products’ head-to-head (SURMOUNT-5), tirzepatide averaged ≈20.2% body-weight reduction versus ≈13.7% for semaglutide. Cost on file: verified compounded floors of $69/mo (semaglutide) versus $97/mo (tirzepatide) — a $28/mo premium for the dual mechanism. Trial evidence belongs to the approved products; the choice belongs to a prescriber looking at you, not an average. Last verified 2026-08-24.

The trial record, attributed properly

Semaglutide (approved product)Tirzepatide (approved product)
Flagship trialSTEP-1: ≈14.9% at 68 weeksSURMOUNT-1: ≈20.9% at 72 weeks (highest dose)
Direct head-to-headSURMOUNT-5: ≈13.7%SURMOUNT-5: ≈20.2%
MechanismGLP-1GIP + GLP-1
Verified compounded floor$69/mo$97/mo

Those trials tested Wegovy and Zepbound — the FDA-approved products. Compounded preparations carry the molecule, not the trial file; that evidence status is the honest asterisk on every compounded comparison, ours included.

Side effects: same family, different intensity curve

Both lead with nausea, constipation, diarrhea, and fatigue, front-loaded in titration. Trial discontinuation-for-adverse-events ran modestly higher for tirzepatide at top doses; plenty of individual patients report the reverse. Tolerability is discovered, not predicted — which is why slow titration and an adjustable provider matter more than the molecule choice.

The decision, honestly framed

Bigger average effect and budget room: tirzepatide has the stronger trial case. Tightest budget: semaglutide’s $69 floor is the market’s entry point, and ≈15% average loss is transformative, not a consolation. History of rough GI tolerance, retinopathy, thyroid-cancer family history, or pregnancy plans: that’s a prescriber conversation before a price conversation — see the safety page. Rankings: semaglutide · tirzepatide.

Update log
  • 2026-08-24 — Page created per the Pass-12 audit; sources inline.