Semaglutide Guide
Semaglutide is a GLP-1 receptor agonist marketed as Ozempic for type 2 diabetes and Wegovy for weight management. In the STEP 1 trial, participants lost an average of 14.9% body weight at 68 weeks. It's a weekly subcutaneous injection that works by mimicking gut hormones that regulate appetite and blood sugar.
What Semaglutide Is
Semaglutide is a synthetic version of glucagon-like peptide-1 (GLP-1), a hormone your intestines produce after eating. When you inject semaglutide, it binds to GLP-1 receptors in your brain, pancreas, and gut.
The FDA approved two branded formulations: Ozempic (2017) for type 2 diabetes at doses up to 2mg weekly, and Wegovy (2021) for chronic weight management at doses up to 2.4mg weekly. Same active ingredient, different approved uses and dose ranges.
Compounded semaglutide versions are also available through telehealth providers when brand-name supplies are limited. These use the same active ingredient but are prepared by compounding pharmacies rather than manufactured by Novo Nordisk.
How It Works
Appetite Suppression
Activates GLP-1 receptors in your brain's appetite control centers, reducing hunger signals and increasing feelings of fullness after eating.
Gastric Slowing
Slows how quickly food leaves your stomach, keeping you fuller longer and reducing post-meal blood sugar spikes.
Insulin Regulation
Stimulates insulin release when blood sugar rises and reduces glucagon secretion, improving overall glucose control.
Clinical Trial Results
The STEP (Semaglutide Treatment Effect in People with obesity) trial program tested 2.4mg weekly semaglutide for weight management. Here's what the evidence shows.
STEP 1: Weight Loss in Adults
New England Journal of Medicine, 2021
Participants without diabetes, average BMI 37.9. 86% of semaglutide group lost at least 5% body weight, compared to 31% in placebo group.
STEP 2: Adults with Type 2 Diabetes
The Lancet, 2021
Lower weight loss compared to STEP 1, likely due to diabetes medications affecting baseline metabolism. Still clinically significant for blood sugar control.
STEP 5: Long-Term Efficacy
Nature Medicine, 2022
Weight loss sustained at two years, suggesting the medication works as long as you continue taking it. Weight typically returns after discontinuation.
Dosing Protocol
Semaglutide requires gradual dose escalation to minimize gastrointestinal side effects. Here's the standard titration schedule for Wegovy (weight management):
Weeks 1-4: 0.25mg
Starting dose to assess tolerance. Not expected to produce significant weight loss yet.
Weeks 5-8: 0.5mg
First increase. Some people notice appetite reduction at this dose.
Weeks 9-12: 1mg
Therapeutic dose for some patients. Your doctor may keep you here if you're seeing results and tolerating it well.
Weeks 13-16: 1.7mg
Penultimate step. Some people stay here as their maintenance dose.
Week 17+: 2.4mg
Maintenance dose used in STEP trials. Continued weekly for ongoing weight management.
Note: If you experience significant nausea or vomiting, your doctor may slow the titration schedule or keep you at a lower dose temporarily. There's no rush—tolerance matters more than reaching maximum dose quickly.
Side Effects
Based on STEP trial data, here's what participants experienced. Side effects typically improve over time as your body adapts.
Most Common (STEP 1 Data)
Serious (Rare but Important)
Pancreatitis
Inflammation of the pancreas. Stop medication and seek medical attention if you experience severe abdominal pain.
Gallbladder disease
Rapid weight loss can increase gallstone risk. Watch for upper right abdominal pain, especially after eating.
Thyroid tumors
Boxed warning based on rodent studies. Not confirmed in humans, but avoid if you have personal/family history of medullary thyroid carcinoma or MEN 2.
Managing Side Effects
- •Eat smaller, more frequent meals instead of large portions
- •Avoid high-fat, greasy, or spicy foods that worsen nausea
- •Stay hydrated, especially if experiencing vomiting or diarrhea
- •Take your injection at night if nausea is worse during the day
- •Talk to your doctor about slowing dose escalation if side effects are severe
Cost & Access
Brand-Name (Wegovy/Ozempic)
Novo Nordisk manufactures both formulations. Wegovy specifically approved for weight management, Ozempic for diabetes (though often prescribed off-label).
Compounded Semaglutide
Prepared by compounding pharmacies during brand-name shortages. Same active ingredient, not FDA-approved as manufactured drugs are.
Who It's For
FDA-Approved Indications
Contraindications
Curious About Tirzepatide?
Tirzepatide (Mounjaro, Zepbound) is a dual GIP/GLP-1 agonist showing higher average weight loss in trials. Compare mechanisms, results, and costs.
Medical Disclaimer
This information is for educational purposes only and does not constitute medical advice. Semaglutide is a prescription medication that requires physician supervision. We are not healthcare providers and cannot recommend whether this medication is appropriate for you.
Clinical trial data presented here is drawn from published research including the STEP trial program. Individual results vary significantly. Talk to your doctor about potential risks, benefits, and alternatives specific to your health situation.