Semaglutide
The Ozempic molecule
GLP-1 Receptor Agonist
Evidence Level: Strong Evidence
Multiple large human trials, FDA approval, established safety profile
Regulatory Status: FDA-approved for diabetes (Ozempic) and weight loss (Wegovy)
Semaglutide is a synthetic version of GLP-1, a hormone your body naturally makes after eating. It tells your brain you're full and slows digestion. Originally developed for type 2 diabetes, it turned out to be remarkably effective for weight loss—so effective that it launched the current GLP-1 revolution.
How It Works
It works through several mechanisms:
• Brain: Reduces appetite and food cravings at the source
• Stomach: Slows emptying so you feel full longer
• Pancreas: Improves insulin release and blood sugar control
• Liver: Reduces glucose production
The net effect: you naturally eat less without the constant battle against hunger that sabotages traditional diets.
Potential Benefits
- 15-17% average weight loss in clinical trials (vs 2-3% for placebo)
- Significantly reduced appetite and food cravings
- Improved blood sugar control and insulin sensitivity
- Cardiovascular benefits (reduced heart attack and stroke risk in some populations)
- Weekly injection (convenient, not daily)
- Well-established safety profile from years of use
Risks & Considerations
- GI side effects are common (nausea, vomiting, diarrhea, constipation)—usually improve over time
- Muscle loss can occur if protein intake is inadequate
- Rare risk of pancreatitis (severe abdominal pain = call doctor immediately)
- Contraindicated with personal/family history of medullary thyroid cancer
- May cause gallbladder problems in some users
- Expensive without insurance ($1,000+/month retail)
- Shortage issues can make it hard to find
Dosing Information
Semaglutide is titrated slowly to minimize side effects. Most protocols start at 0.25mg weekly for 4 weeks, then increase gradually.
- •Starting dose: 0.25mg/week (this is sub-therapeutic—for adjustment only)
- •Typical escalation: 0.25 → 0.5 → 1.0 → 1.7 → 2.4mg
- •Each dose increase = 4 weeks minimum
- •Maximum approved dose for weight loss: 2.4mg/week
- •Never start at a high dose—GI side effects will be severe
Practical Tips
- 1Inject on the same day each week (pick a day and stick to it)
- 2Rotate injection sites: stomach, thigh, or upper arm
- 3Store in refrigerator before first use; can keep at room temp for up to 28 days after
- 4Eat protein first at every meal to protect muscle mass
- 5Stay ahead of constipation with fiber and water
- 6If you miss a dose: take it within 5 days, then resume schedule
Key Research
STEP 1 Trial
New England Journal of Medicine, 2021
Participants lost an average of 14.9% body weight vs 2.4% with placebo over 68 weeks.
SELECT Trial
New England Journal of Medicine, 2023
Reduced cardiovascular events (heart attack, stroke) by 20% in people with obesity and heart disease.
Related Goals
Related Treatments
Disclaimer: This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider before starting any treatment. Evidence levels and regulatory status can change—this content was last updated November 2024.