The most-asked comparison on the site, and the one with the most evidence behind it. Tirzepatide hits two incretin receptors, GLP-1 and GIP; semaglutide hits one. In the only head-to-head randomized trial (SURMOUNT-5), tirzepatide produced more weight loss.
Side by side
| Tirzepatide | Semaglutide | |
|---|---|---|
| Class | GLP-1 / GIP dual agonist | GLP-1 agonist |
| Status | FDA approved | FDA approved |
| Route | Subcutaneous injection | Subcutaneous injection |
| Typical vials | 5 mg, 10 mg, 15 mg, 30 mg, 60 mg | 2 mg, 5 mg, 10 mg, 15 mg |
| Dose range | 2.5 mg to 15 mg | 0.25 mg to 2.4 mg |
| Frequency | Once weekly | Once weekly |
| Half-life | ~5 days | ~7 days |
| Dosing unit | milligrams | milligrams |
Pharmacokinetics
What the evidence supports
These grade how well each outcome has been studied in humans, never how well either compound works. A strong grade can sit on a negative result.
Both top out at the same tier of evidence: Human RCT. Where they differ is in which outcomes have been asked about, not in how well either has been studied overall.
Tirzepatide
| Outcome | Evidence |
|---|---|
| Cardiovascular event reduction | Human RCT |
| Glycemic control in type 2 diabetes | Human RCT |
| Obstructive sleep apnea severity | Human RCT |
| Weight loss | Human RCT |
| Lean mass preservation | Human, observational |
Semaglutide
| Outcome | Evidence |
|---|---|
| Cardiovascular event reduction | Human RCT |
| Chronic kidney disease progression | Human RCT |
| Glycemic control in type 2 diabetes | Human RCT |
| MASH / liver histology | Human RCT |
| Weight loss | Human RCT |
How to choose
Tirzepatide has the better weight-loss data
It beat semaglutide in a direct randomized comparison, not just across separate trials. Cross-trial comparison is unreliable; this one was head to head.
Semaglutide has the longer cardiovascular record
SELECT established cardiovascular event reduction in people without diabetes. Tirzepatide's outcomes program is younger, so the difference is in how long each has been studied, not a demonstrated difference in effect.
Tolerability is individual
Both are dominated by gastrointestinal side effects that drive most discontinuation. Which one an individual tolerates is not predictable from the trial averages.
Neither trial program used compounded material
Every number above comes from pharmaceutical product. None of it transfers automatically to research-grade vials of unverified content, which is what this site's reconstitution math is usually applied to.
At the syringe
At the default setup on each compound's own page, a 10 mg vial in 2 mL puts 50 mcg on every insulin unit, while a 5 mg vial in 2 mL puts 25 mcg on every unit. That is the number that decides whether a dose lands on a readable mark, and it is set by how much water goes in, not by the compound.