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Pick up to 3 compounds to see protocols, mechanisms, study endpoints and safety findings side by side.
Peptijournal · Semaglutide vs Retatrutide · https://peptijournal.com/compare?c=semaglutide,retatrutide · Printed
01Protocol
Semaglutide
- Start
- 0.25 mg
- Range
- 0.25–2.4 mg
- Frequency
- Once weekly
- Cycle
- Ongoing, titrated every 4 weeks
- Vials
- 3 / 5 / 10 mg
- Titration
- Weeks 1–4: 0.25 mg
- Weeks 5–8: 0.5 mg
- Weeks 9–12: 1.0 mg
- Weeks 13–16: 1.7 mg
- Weeks 17+: 2.4 mg
Retatrutide
- Start
- 2 mg
- Range
- 2–12 mg
- Frequency
- Once weekly
- Cycle
- Ongoing, titrated every 4 weeks
- Vials
- 10 / 20 / 30 mg
- Titration
- Weeks 1–4: 2 mg
- Weeks 5–8: 4 mg
- Weeks 9–12: 8 mg
- Weeks 13+: 12 mg (highest trial arm)
02Quick calculator
Semaglutide
Retatrutide
03Mechanism of action
Semaglutide
Semaglutide is a GLP-1 receptor agonist modified with a fatty-acid side chain that binds albumin, giving it a roughly week-long half-life. GLP-1 receptor activation increases glucose-dependent insulin secretion, lowers glucagon, slows gastric emptying and acts on brain appetite centres.
Retatrutide
Retatrutide (LY3437943) is a single peptide agonist of three receptors: GIP, GLP-1 and glucagon. Adding glucagon-receptor activity is studied for increasing energy expenditure and liver-fat effects on top of the appetite effects of GIP/GLP-1 agonism.
04Study endpoints
Semaglutide
- STEP 1 (adults with obesity, no diabetes): mean body-weight change of −14.9% vs −2.4% with placebo at week 68.
- SUSTAIN-6 (type 2 diabetes): major cardiovascular events in 6.6% vs 8.9% with placebo (hazard ratio 0.74).
- SELECT (cardiovascular disease + overweight, no diabetes): primary cardiovascular events in 6.5% vs 8.0% (hazard ratio 0.80).
Retatrutide
- Phase 2 obesity trial (338 adults): mean weight change at 48 weeks ranged from −8.7% to −24.2% across arms vs −2.1% with placebo.
- In the highest arm, 83% of participants lost 15% or more of body weight at 48 weeks, vs 2% on placebo.
- Preclinical and early clinical work describes glycaemic and weight effects from combined triple-receptor agonism.
05Safety & regulatory findings
Semaglutide
- FDA-approved (as Ozempic, Wegovy and Rybelsus) for specific indications; research-grade material is not an approved product.
- Gastrointestinal effects were the most common adverse events; in SELECT, 16.6% stopped treatment for adverse events vs 8.2% on placebo.
- SUSTAIN-6 reported more diabetic retinopathy complications in the semaglutide group.
Retatrutide
- Investigational: not approved by the FDA or EMA for any indication. Phase 3 trials are ongoing.
- Phase 2 adverse events were mainly gastrointestinal and dose-related; heart-rate increases were also reported.