Semaglutide

Acylated GLP-1 receptor agonist with 94% homology to native GLP-1. Binds the GLP-1 receptor on pancreatic beta cells, enhancing glucose-dependent insulin secretion while suppressing glucagon. Also acts on hypothalamic neurons to reduce appetite via delayed gastric emptying and central satiety signaling.

Half-life

7 days (168 hours)

Bioavailability

89% (SC), ~1% (oral with SNAC coformulation)

Route

subcutaneous, oral

Evidence tier

T1 — Multiple RCTs

Optimization pillars

fat-loss · cellular-health

References

4 peer-reviewed

Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative

0.25–0.5 mg/week SC

Titration initiation (weeks 1-8)

moderate

1–1.7 mg/week SC

Glycemic control and moderate weight loss

aggressive

2.4 mg/week SC

Maximum approved dose for obesity (Wegovy)

Monitoring

fasting-glucose
hba1c
fasting-insulin
homa-ir
lipid-panel
thyroid-panel
alt
ast
creatinine
egfr

Contraindications

medullary-thyroid-carcinoma
men2-syndrome
pancreatitis-history
severe-gastroparesis
diabetic-retinopathy-active

References

PMID:33567185Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) — N Engl J Med, 2021
PMID:34706925Two-Year Effects of Semaglutide in Adults with Overweight or Obesity (STEP 5) — Nat Med, 2022
PMID:36351458Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SELECT) — N Engl J Med, 2023
PMID:28930209Semaglutide and Cardiovascular Outcomes in Type 2 Diabetes (SUSTAIN-6) — N Engl J Med, 2016

Notes

Semaglutide changed the metabolic landscape permanently. Not because it was the first GLP-1 agonist — liraglutide existed for years. Because the 168-hour half-life made weekly dosing possible, which made compliance possible, which made population-scale fat loss achievable for the first time. The molecule is not the breakthrough. The pharmacokinetics are the breakthrough. STEP trials showed 15-17% body weight reduction at 2.4mg. SELECT showed cardiovascular mortality reduction independent of diabetes status. This compound moved from endocrinology into cardiology in under five years. The titration protocol matters more than the target dose. Most adverse events cluster in people who escalate too fast.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

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