Semaglutide: The Original GLP-1 Agonist
Semaglutide was developed by Novo Nordisk and first approved in 2017 for type 2 diabetes (as Ozempic). Its approval for chronic weight management (as Wegovy) came in 2021, following the STEP trial series that demonstrated 15% average body weight reduction over 68 weeks.
The molecule is the same across Ozempic and Wegovy. The clinical difference is the maximum dose: Ozempic tops out at 2.0mg/week (for diabetes management), while Wegovy goes to 2.4mg/week (for weight loss). Some patients prescribed Ozempic for off-label weight management find the 2.0mg cap less effective than the full 2.4mg Wegovy dose.
Tirzepatide: Two Targets, Better Results on Average
Eli Lilly's tirzepatide (Mounjaro for diabetes, Zepbound for weight loss) is a "twincretin" — it activates both GLP-1 and GIP receptors simultaneously. GIP (glucose-dependent insulinotropic polypeptide) is another incretin hormone that synergizes with GLP-1 signaling.
The SURMOUNT-1 trial showed average weight loss of 22.5% at the highest dose (15mg) — significantly greater than semaglutide in its trials. However, head-to-head comparison trials are limited, and individual response varies considerably. Some patients respond better to semaglutide. The right medication is determined by physician judgment on your metabolic profile, tolerance, and cost situation.
Compounded Semaglutide: The Cost Question
When brand-name GLP-1 medications entered shortage status, compounding pharmacies began producing compounded semaglutide and tirzepatide. The FDA permits compounding during shortage periods, but with important distinctions.
503B vs. 503A Pharmacies
503B pharmacies (outsourcing facilities): Operate under more FDA oversight, produce larger batches, subject to inspections. Generally considered higher quality for compounded GLP-1 medications.
503A pharmacies (traditional compounding): Produce patient-specific compounds, less oversight. Quality can vary more significantly between pharmacies.
If you're considering compounded GLP-1:
- Ask which pharmacy your provider uses and whether it's 503B or 503A
- Compounded semaglutide is typically $200-$400/month vs. $900-$1,600 for brand-name
- Efficacy should be equivalent if the pharmacy is using pharmaceutical-grade ingredients
- Quality verification: ask about certificate of analysis (CoA) for each batch
- FTC has taken action against providers making misleading claims — use providers with physician oversight, not "weight loss subscription boxes"
Which Medication Should You Ask Your Doctor About?
This is a physician decision — not something a website can appropriately prescribe. But here are the questions worth raising:
- Do I meet the criteria for anti-obesity medication? (BMI ≥30, or ≥27 with a weight-related condition)
- Given my blood glucose levels, which medication makes more sense as a starting point?
- Is compounded semaglutide appropriate in my situation, and which pharmacy do you use?
- What monitoring will you be doing for thyroid, pancreatic enzymes, and lean mass?
- What's the plan if I want to discontinue — do we taper?