[educational] GLP-1 receptor agonist; an analog of endogenous GLP-1 (a ~31-aa peptide). Native GLP-1 has a ~2-min half-life (cleaved by DPP-4); semaglutide is engineered (position-8 swap for DPP-4 resistance + a position-26 fatty-acid chain giving reversible albumin binding) for a ~7-day half-life. Same molecule whether injected or oral. FDA-approved for type-2 diabetes and obesity. — Oral GLP-1 review
Mechanisms
[educational] Acts via GLP-1 Agonism across many tissues (pancreas, gut, hypothalamus, immune, kidney, endothelium, brain) — see that note. — Oral GLP-1 review
Evidence
[educational]subQ bioavailability 89% vs oral 1–2% (needs SNAC + strict fasted, ≤4 oz water, no food 30 min+ after). Weight loss: oral 25 mg → 13.6%, 50 mg → 15.1%, subQ 2.4 mg → 14.9%, subQ 7.2 mg → 18.7% (plateau above 7.2 mg subQ / 25–50 mg oral). A1C: oral 25/50 mg ≈ subQ (−1.8 to −2.0%). −14% MACE (no oral-vs-subQ difference). subQ has proven edge in CKD and fatty-liver disease. — Oral GLP-1 review
[literature] Emerging oncology signal: GLP-1 RAs associated with reduced metastatic progression of obesity-related cancers (ASCO 2026) and better breast-cancer survival in obesity/T2D (JAMA Netw Open 2026, HR 0.35/0.09). Observational — not causal yet. — SOURCE-asco2026-glp1-cancer-progression, SOURCE-glp1-breast-cancer-outcomes
[literature]Lower breast-cancer INCIDENCE (prevention axis; ASCO 2026 Abstract 10506, JCO Oncology Practice): in 94,827 cancer-free women (BMI≥25), GLP-1 RA exposure → ~25–37% lower odds of developing breast cancer (matched OR 0.746, P<.0005); signal reportedly persisted after adjusting for weight loss. Observational. — SOURCE-glp1-breast-cancer-incidence-mcdonald-2026
Anecdotes
[educational] Ranked #1 longevity (GLP-1 class) — meta-analyses (100k pts): −12% all-cause death; obesity-no-diabetes −51–77%. Beyond weight: anti-inflammatory, −45% dementia risk, ↑mito/↓oxidative, ↓senescence/↑autophagy. Animal: low-dose from mid-life gave rapamycin-like aging benefits without weight change → low-dose from late-30s+ may aid longevity (human data pending). — Longevity Top-5
Physician protocols
[protocol]Start low, titrate slow (limits GI side effects, preserves muscle). Oral must be taken overnight-fasted with ≤4 oz water, no food 30 min+ after, swallowed whole. ~56% discontinue oral within 1 year (regimen burden). — Oral GLP-1 review
Practical notes
[educational] High oral absorption variability (up to ~137% day-to-day in one person; ~56% between people) — non-response may be absorption, not dose. — Oral GLP-1 review