Orforglipron vs Tirzepatide
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
OrforglipronGLP-1 / Weight Loss Agonists
Tirzepatide- Summary
- 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.
- Tirzepatide is an FDA-approved dual GIP/GLP-1 receptor agonist that produces greater weight loss than semaglutide in head-to-head trials. SURMOUNT-1 trial showed average 21% body weight reduction at 72 weeks at the highest dose. Marketed as Mounjaro (diabetes) and Zepbound (obesity).
- Half-Life
- ~12 hours (once-daily oral dosing)
- ~5 days
- Admin Route
- Oral
- SubQ
- Research
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- Typical Dose
- 12 mg → 24 mg → 36 mg → 45 mg
- 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg
- Frequency
- Once daily
- Once weekly, subcutaneous
- Key Benefits
- 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
- Average 21% body weight reduction at highest dose (SURMOUNT-1)
- Superior to semaglutide in head-to-head SURPASS trials
- Dual GIP/GLP-1 mechanism for enhanced metabolic control
- Significant reduction in HbA1c for type 2 diabetes
- Improved cardiovascular risk markers
- Reduces visceral fat preferentially
- FDA-approved for T2DM (Mounjaro) and obesity (Zepbound)
- Weekly dosing
- Side Effects
- Nausea (most common, dose-dependent)
- Vomiting
- Diarrhea
- Decreased appetite
- +2 more
- Nausea (most common during titration)
- Vomiting
- Diarrhea or constipation
- Abdominal pain
- +3 more
- Stacks With
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