Retatrutide vs Orforglipron
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
RetatrutideGLP-1 / Weight Loss Agonists
Orforglipron- Summary
- Retatrutide is an investigational triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Phase 2 trials showed an unprecedented average 24% body weight reduction at 48 weeks — exceeding any approved medication to date. It is in Phase 3 trials as of 2024.
- Orforglipron is an oral, once-daily small-molecule GLP-1 receptor agonist developed by Eli Lilly. Unlike injectable GLP-1 peptides, it is a non-peptide compound absorbed orally without food restrictions, representing a major convenience advancement. Phase 2 trials showed up to 9.4% weight loss at 36 weeks, and Phase 3 trials (ATTAIN program) are ongoing for obesity and type 2 diabetes.
- Half-Life
- ~10–12 days
- ~12 hours (once-daily oral dosing)
- Admin Route
- SubQ
- Oral
- Research
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- Typical Dose
- 0.5 mg → 1 mg → 2 mg → 4 mg → 8 mg → 12 mg
- 12 mg → 24 mg → 36 mg → 45 mg
- Frequency
- Once weekly
- Once daily
- Key Benefits
- ~24% body weight reduction at 48 weeks in Phase 2 (highest dose)
- Superior to both semaglutide and tirzepatide in early trial comparisons
- Triple receptor mechanism addresses multiple obesity pathways
- Significant reduction in liver fat (MASH/NAFLD indication being studied)
- Improved cardiovascular and metabolic markers
- Once-weekly dosing
- Potential for greatest weight loss of any currently investigated compound
- Oral pill — no injections required
- Once-daily dosing without food restrictions (unlike oral semaglutide)
- Up to 9.4% body weight reduction in Phase 2 at 36 weeks
- Significant HbA1c reduction in type 2 diabetes trials
- Small-molecule stability — no cold chain requirements
- Broadens access for injection-averse patients
- Potential class-defining convenience advantage over injectable GLP-1s
- Side Effects
- Nausea and vomiting (common during titration, similar to semaglutide/tirzepatide)
- Diarrhea
- Constipation
- Heart rate increase (from glucagon receptor agonism)
- +2 more
- Nausea (most common, dose-dependent)
- Vomiting
- Diarrhea
- Decreased appetite
- +2 more
- Stacks With
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