Orforglipron
Also known as: LY-3502970
Oral Small-Molecule GLP-1 Receptor Agonist | Weight Loss & Diabetes
Overview
First oral non-peptide GLP-1 completing Phase 3 trials. Achieves substantial weight loss without injections, refrigeration, or dietary restrictions, with clinical evidence of 12.4% weight reduction at 72 weeks.
Key benefits
- Significant weight loss (up to 12.4% at 72 weeks)
- Robust diabetes control (HbA1c reduction 1.3-1.6%)
- Once-daily oral tablet format
- No refrigeration or food restrictions required
- Reduced cardiovascular risk markers
Mechanism of action
Small-molecule GLP-1 receptor agonist with biased signaling preferentially activating G protein/cAMP pathways, enhancing insulin secretion, suppressing glucagon, delaying gastric emptying, and reducing appetite while minimizing receptor desensitization. 79.1% oral bioavailability with 29-49 hour half-life.
Molecular data
- Type
- Small-molecule GLP-1R agonist
- Half-life
- 25-68 hours
Sequence
Not applicable - synthetic small molecule
Indications
What the research community uses this compound for, with self-reported effectiveness.
Weight Loss
Type 2 Diabetes
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Delivery method
| Protocol | Dose | Frequency | Duration |
|---|---|---|---|
| — | 3mg daily | Once daily, any time | — |
| — | 12mg daily | Once daily, any time | — |
| — | 36mg daily | Once daily, any time | — |
| — | 6mg daily | Once daily, any time | — |
| — | 36mg daily | Once daily, any time | — |
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
Common side effects
- Diarrhea (more prevalent than with injectable GLP-1s)
- Nausea (typically improves after first month)
- Appetite reduction
Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- Pregnancy and breastfeeding
Monitoring
- Monitor for signs of acute pancreatitis
- Adjust other diabetes medications to prevent hypoglycemia
- Monitor for gallbladder disease symptoms with rapid weight loss
- Watch for suicidal thoughts or significant mood changes