Orforglipron (LY3502970)
Oral non-peptide small-molecule GLP-1 receptor agonist. First oral GLP-1 to show clinically meaningful weight loss in Phase 3: 12.4% body weight reduction at 72 weeks (ATTAIN-1, 36 mg).
This compound sits in research-grey territory. The caveats below carry more weight than for FDA-approved entries — read them.
Unlike peptide GLP-1 agonists (semaglutide, retatrutide), orforglipron is a small molecule — it crosses the GI tract without degradation and doesn't require injection. Lilly Phase 3 program (ATTAIN-1, -2, -3, -MAINTAIN): ATTAIN-1 published NEJM 2026 (36 mg, 72 weeks): 27.3 lbs / 12.4% weight loss, 59.6% achieved ≥10% reduction. ATTAIN-2 (T2D): all doses met primary glycemic endpoints. Lilly filed global regulatory submissions 2026 — could become the first oral GLP-1 obesity drug. The oral-vs-injectable wedge is real: 'I hate needles' cohort is large and largely unreached by current GLP-1 adoption.
GI side effects are the primary class risk (nausea, diarrhea, vomiting) — same as injectable GLP-1 class per ATTAIN-1 safety profile. CYP3A4 interaction risk — hormonal contraceptives, certain antifungals, and HIV medications all interact. Small-molecule status means it could theoretically appear in grey-market oral research compounds before FDA approval — Stack strongly cautions against this: dosing, impurity profiles, and titration schedules outside clinical trials are unvalidated.
External links to PubMed searches, ClinicalTrials.gov, and FDA materials. We do not host papers — we point at canonical sources.
Not FDA-approved. Lilly submitted global regulatory filings 2026. Likely FDA-approved 2027 if review proceeds normally. No 503A compounding path (not a peptide; small-molecule Bulks List criteria differ).
Distilled themes from named communities — Reddit threads, forums, creator commentary. Not direct quotes; not clinical evidence. Useful for calibrating expectations against what real self-experimenters report.
The 'I hate needles' cohort is loud here. Cohort consensus: smaller weight-loss % than retatrutide or tirzepatide, but the oral route removes the biggest adoption barrier. Primary-care-prescribable GLP-1 is the macro story — no injection training needed. Post-NEJM publication, user interest spiked. Grey-market sourcing discussed but dismissed — dosing validation is too thin.