Semaglutide (Ozempic / Wegovy)
The most clinically validated pharmacological weight loss agent available. A synthetic GLP-1 analogue with 94% homology to human GLP-1, modified for extended half-life. STEP trials demonstrate 15–17% body weight reduction; the SELECT trial demonstrated 20% reduction in cardiovascular events. Increasingly used in longevity protocols for metabolic optimisation.
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What Is Semaglutide?
Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with 94% amino acid homology to human GLP-1, modified with a C18 fatty acid chain that enables albumin binding and extends its half-life to approximately 7 days — enabling once-weekly dosing.
It is available under two brand names with different approved indications: Ozempic (approved for type 2 diabetes) and Wegovy (approved for obesity/overweight with comorbidity). The compounds are identical; the indications, approved doses, and pen delivery systems differ.
Clinical Evidence
The STEP (Semaglutide Treatment Effect in People with Obesity) trial programme is the most extensive weight loss trial programme conducted. STEP 1 (Wilding et al., NEJM 2021) demonstrated 15% mean body weight loss over 68 weeks in 1961 adults with obesity — results without pharmaceutical parallel in clinical history.
The SELECT trial (Lincoff et al., NEJM 2023) enrolled 17,604 adults with cardiovascular disease and obesity (without diabetes) and showed 20% reduction in major cardiovascular events — establishing semaglutide's cardiovascular mortality benefit independent of glucose-lowering.
Biohacker Protocol
The biohacker approach differs from standard clinical use: lower starting doses (0.125mg/week), slower titration, mandatory muscle preservation strategies (1.6–2g/kg protein + resistance training + creatine 5g/day), and a cycling approach to maintain receptor sensitivity.
Muscle Preservation
25–35% of weight lost on semaglutide is lean mass without protective strategies. Resistance training 3x/week + high protein intake + creatine supplementation are non-negotiable components of any intelligent semaglutide protocol.
Related Research
Stacking Interactions
How Semaglutide (Ozempic / Wegovy) interacts with other compounds
Safety Profile — Tier B
Generally safe — moderate evidence
Contraindications
- ●Personal or family history of medullary thyroid carcinoma (MTC)
- ●Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- ●History of pancreatitis
- ●Pregnancy and breastfeeding
- ●Severe gastrointestinal disease
Side Effects
- ●Nausea — very common, especially during titration (dose-dependent)
- ●Vomiting and diarrhoea
- ●Constipation
- ●Reduced appetite (intended effect)
- ●Fatigue during titration
- ●Rare: pancreatitis, gallbladder disease