Semaglutide vs Tirzepatide
The most-compared pair in metabolic research, including the first direct head-to-head obesity trial.
Research use only. A summary of published literature for educational reference — not medical advice and not a guide to human use.
The short version
Semaglutide is a GLP-1-only agonist with the most mature cardiovascular outcome data. Tirzepatide adds GIP activity and produced greater mean weight and HbA1c reductions in direct head-to-head trials.
At a glance
Class
GLP-1 receptor agonist
GIP / GLP-1 dual agonist
Approval status
FDA-approved (Ozempic, Wegovy, Rybelsus)
FDA-approved (Mounjaro, Zepbound)
Half-life
About 7 days
About 5 days
Head-to-head
SURMOUNT-5: −13.7% at 72 weeks
SURMOUNT-5: −20.2% at 72 weeks
Outcome data
SELECT: 20% fewer major cardiovascular events
Cardiovascular outcome trial reported more recently
Research vial sizes
3 / 5 / 10 mg
10 / 15 / 30 mg
01How they work
Semaglutide mimics GLP-1, slowing gastric emptying, increasing insulin release and acting on appetite centres in the brain. Tirzepatide binds both GLP-1 and GIP receptors; GIP co-agonism is thought to add to the appetite and insulin effects.
02What studies measured
STEP 1 reported −14.9% mean weight change with semaglutide at 68 weeks. SURPASS-2 compared both in type 2 diabetes and found larger HbA1c and weight reductions with tirzepatide.
SURMOUNT-5, the direct obesity comparison, reported −20.2% with tirzepatide versus −13.7% with semaglutide at 72 weeks.
03Reported side effects
The profiles are similar: gastrointestinal events dominate and are most common during escalation. Discontinuation for adverse events was low in both arms of the head-to-head trials. Both labels carry thyroid C-cell tumour warnings based on rodent data.
04Approval & evidence status
Both are approved. Semaglutide also has an oral form and an approved cardiovascular risk-reduction indication based on SELECT.
Citations
- [1]Phase 3 randomized controlled trial2021
Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
Wilding JPH, et al. N Engl J Med, 2021.
Read paper ↗ - [2]Phase 3 head-to-head randomized trial2021
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)
Frías JP, et al. N Engl J Med, 2021.
Read paper ↗ - [3]Phase 3b head-to-head randomized trial2025
Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)
Aronne LJ, et al. N Engl J Med, 2025.
Read paper ↗ - [4]Cardiovascular outcomes trial2023
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)
Lincoff AM, et al. N Engl J Med, 2023.
Read paper ↗
Research use only. A summary of published literature for educational reference — not medical advice and not a guide to human use.