Metabolic Longevity Protocol
Advanced metabolic optimisation combining Semaglutide, Berberine, Acarbose, and NMN — targeting body composition, insulin sensitivity, glucose metabolism, and NAD+ restoration for comprehensive metabolic longevity.
Daily Schedule
Timing and dosage for each step
Weekly
1 mg
0.25mg/week initially, titrate to 1-2mg/week, subcutaneous injection
With meals
With meals
Morning
Protocol Overview
Metabolic dysfunction — hyperinsulinaemia, insulin resistance, visceral adiposity, and postprandial glucose dysregulation — is not merely a disease risk. It is an accelerant of ageing through mTOR overactivation, mitochondrial impairment, AGE (advanced glycation end-product) formation, and chronic inflammation.
This protocol uses Semaglutide's clinical-grade weight loss and cardiovascular protection as the primary intervention, with three supporting compounds that address complementary metabolic mechanisms and longevity pathways.
The Four-Compound Approach
Semaglutide (Ozempic/Wegovy) — GLP-1 receptor agonist with the most robust clinical evidence for weight loss (15–17% body weight, STEP trials) and cardiovascular protection (20% reduction in MACE, SELECT trial). The primary driver of body composition change in this protocol.
Berberine (500mg 3x/day) — AMPK activator and indirect mTOR inhibitor. During the Semaglutide cycle, Berberine enhances insulin sensitivity and provides the metabolic benefits of mTOR inhibition through AMPK. After Semaglutide cycling off, Berberine maintains metabolic improvements as a bridge compound.
Acarbose (25–50mg with carbohydrate meals) — alpha-glucosidase inhibitor that flattens postprandial glucose curves. Synergistic with Semaglutide's gastric emptying delay for glucose management. Independently demonstrated 22% lifespan extension in male ITP mice.
NMN (500mg/day) — restores NAD+ levels that decline with obesity and metabolic dysfunction. NAD+ is essential for sirtuin activation (metabolic regulators), mitochondrial function, and DNA repair. Weight loss itself raises NAD+ — NMN amplifies this effect.
Protocol Phases
Phase 1: Semaglutide Loading (Weeks 1–20) Semaglutide 0.25mg/week → titrate to maintenance dose (typically 1–2mg/week for biohacker purposes). Berberine, Acarbose, and NMN throughout.
Phase 2: Semaglutide Off-Cycle (Weeks 21–32) Discontinue Semaglutide. Maintain Berberine, Acarbose, and NMN as metabolic support. CGM monitoring recommended to track glucose response without GLP-1 agonism.
Phase 3: Evaluate and Restart Re-evaluate body composition, metabolic markers, and cardiovascular risk factors. Restart Semaglutide if indicated by physician assessment.
Critical: Muscle Preservation
Semaglutide causes significant lean mass loss without protective strategies. Non-negotiable additions:
- Protein: 1.6–2g/kg bodyweight daily
- Resistance training: 3x/week minimum
- Creatine: 5g/day
- Regular DEXA scans to monitor body composition
Biomarkers
Monthly: fasting glucose, fasting insulin, HbA1c, body weight, waist circumference. Every 3 months: DEXA scan (lean mass vs fat mass), lipid panel, hs-CRP, liver enzymes.