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Pick up to 3 compounds to see protocols, mechanisms, study endpoints and safety findings side by side.
Peptijournal · Retatrutide vs Tirzepatide · https://peptijournal.com/compare?c=retatrutide,tirzepatide · Printed
01Protocol
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)
Tirzepatide
- Start
- 2.5 mg
- Range
- 2.5–15 mg
- Frequency
- Once weekly
- Cycle
- Ongoing, titrated every 4 weeks
- Vials
- 10 / 15 / 30 mg
- Titration
- Weeks 1–4: 2.5 mg
- Weeks 5–8: 5 mg
- Weeks 9–12: 7.5 mg
- Weeks 13–16: 10 mg
- Weeks 17–20: 12.5 mg
- Weeks 21+: 15 mg (max studied)
02Quick calculator
Retatrutide
Tirzepatide
03Mechanism of action
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.
Tirzepatide
Tirzepatide is a single peptide that activates both the GIP and GLP-1 receptors (a 'twincretin'). It carries a fatty-acid chain for albumin binding and once-weekly exposure. Combined GIP/GLP-1 signalling affects insulin and glucagon secretion, gastric emptying and appetite.
04Study endpoints
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.
Tirzepatide
- SURMOUNT-1 (obesity, no diabetes): mean weight change of −15.0% to −20.9% across dose arms vs −3.1% with placebo at week 72.
- SURPASS-2 (type 2 diabetes): every tirzepatide arm lowered HbA1c more than semaglutide (−2.01 to −2.30 vs −1.86 points).
- SURMOUNT-5 (head-to-head, obesity): −20.2% weight change vs −13.7% with semaglutide at week 72.
05Safety & regulatory findings
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.
Tirzepatide
- FDA-approved (as Mounjaro and Zepbound) for specific indications; research-grade material is not an approved product.
- Gastrointestinal events were the most common adverse effects and occurred mostly during dose escalation.