Tirzepatide vs semaglutide
Every row cites its source. Where a cell reflects our own reading of the evidence rather than an external source, the row says so.
| Dimension | Tirzepatide | Semaglutide (Wegovy / Ozempic) | Source |
|---|---|---|---|
| Mechanism | Dual GIP and GLP-1 receptor agonist | Selective GLP-1 receptor agonist (94% homology to human GLP-1) | source |
| FDA-approved uses | Type 2 diabetes (Mounjaro, 2022); chronic weight management (Zepbound, 2023); moderate to severe OSA with obesity (2024) | Type 2 diabetes (Ozempic); chronic weight management and cardiovascular risk reduction in established CV disease (Wegovy) | source |
| Head-to-head weight loss (obesity, no diabetes) | -20.2% mean at 72 weeks (SURMOUNT-5) | -13.7% mean at 72 weeks (semaglutide 2.4 mg, same trial) | source |
| Waist circumference (head-to-head) | -18.4 cm | -13.0 cm | source |
| Head-to-head in type 2 diabetes (SURPASS-2) | HbA1c -2.01 to -2.30 points; up to 5.5 kg more weight loss; noninferior and superior | HbA1c -1.86 points at the 1 mg diabetes dose | source |
| Cardiovascular outcomes evidence | Noninferior to dulaglutide in T2D (HR 0.92, superiority not shown); placebo-controlled obesity CV trial (SURMOUNT-MMO, n=15,374) reads out around 2027 | SELECT: 20% relative reduction in major CV events vs placebo (HR 0.80) in obesity with CV disease; approved CV indication | source |
| Most common side effects | GI-led: nausea 25 to 29%, diarrhea 19 to 23%, vomiting 8 to 13% (vs placebo 8%, 8%, 2%) | GI-led: nausea, diarrhea, vomiting, constipation among reactions in 5% or more; in SURPASS-2 the head-to-head GI rates were similar (nausea 17 to 22% vs 18%) | source |
| Dosing and titration | Start 2.5 mg weekly; 2.5 mg steps every 4 or more weeks; maintenance 5, 10, or 15 mg | Start 0.25 mg weekly; steps every 4 weeks (0.5, 1, 1.7); maintenance 2.4 mg (or 1.7 mg) from week 17 | source |
| Missed-dose window | Take within 4 days (96 hours); otherwise skip | Take only if next dose is more than 48 hours away; otherwise skip | source |
Two weekly incretin injectables, one receptor apart. Tirzepatide activates GIP and GLP-1; semaglutide activates GLP-1 alone. In the only head-to-head obesity trial, tirzepatide reduced weight more (20.2% vs 13.7% at 72 weeks); semaglutide holds the cardiovascular-outcome indication tirzepatide does not yet have. Every row below is cited.
Cross-trial numbers are never directly comparable; only SURMOUNT-5 and SURPASS-2 measured these drugs head to head, and SURMOUNT-5 was open-label. SURPASS-2 used semaglutide 1 mg (the diabetes dose available at the time), not 2.4 mg. Semaglutide's SELECT cardiovascular result has no published tirzepatide equivalent against placebo yet; SURPASS-CVOT used an active comparator that itself reduces CV events.