Semaglutide vs Retatrutide
One receptor versus three: the established GLP-1 benchmark against the leading investigational triple agonist.
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 approved and has years of outcome data. Retatrutide targets GLP-1, GIP and glucagon receptors and reported roughly 10 percentage points more mean weight loss in its phase 2 trial than semaglutide did in STEP 1, though the two were never tested against each other.
At a glance
Class
GLP-1 receptor agonist
GIP / GLP-1 / glucagon triple agonist
Approval status
FDA-approved
Investigational (phase 3)
Half-life
About 7 days
About 6 days
Headline trial
STEP 1: −14.9% at 68 weeks
Phase 2: −24.2% at 48 weeks (top arm)
Research vial sizes
3 / 5 / 10 mg
10 / 20 / 30 mg
01How they work
Semaglutide acts only on the GLP-1 receptor. Retatrutide adds GIP and glucagon receptor activity; glucagon signalling is studied for its effect on energy expenditure and liver fat.
02What studies measured
STEP 1 enrolled 1,961 adults and reported −14.9% versus −2.4% with placebo. The retatrutide phase 2 trial enrolled 338 adults over a shorter period. Cross-trial comparisons are indicative only.
03Reported side effects
Both show the incretin-class gastrointestinal pattern. Retatrutide also reported transient heart-rate increases. Long-term safety data exist only for semaglutide.
04Approval & evidence status
Semaglutide is approved for diabetes, weight management and cardiovascular risk reduction. Retatrutide is investigational.
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 2 randomized controlled trial2023
Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff AM, et al. N Engl J Med, 2023.
Read paper ↗ - [3]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.