Semaglutide (GLP-1), considered.
GLP-1 medications represent the largest pharmacological shift in obesity medicine in 60 years. The clinical effect is real and durable — provided the medication continues. The question now is who should take it, who should not, and how to use it well.
What it does.
Semaglutide is a glucagon-like peptide-1 receptor agonist. It mimics a gut hormone the body produces in response to food, slowing gastric emptying, reducing appetite at the brain level, and improving insulin sensitivity. The effect on appetite is the dominant mechanism for weight loss.
Average weight loss in trials: 12–15% of body weight at 68 weeks at the maximum 2.4 mg dose. Real-world adherence and dosing tend to be lower; expected real-world result is closer to 8–12%.
Who is a candidate.
FDA labeling (Wegovy): BMI ≥30, or BMI ≥27 with at least one weight-related comorbidity (hypertension, dyslipidemia, type 2 diabetes, sleep apnea). Off-label prescribing for cosmetic weight loss is widespread but ethically and clinically contested.
Strong contraindications: personal or family history of medullary thyroid carcinoma, MEN2, severe gastroparesis, acute pancreatitis history. Pregnancy is a contraindication. Patients with active gallbladder disease should be evaluated carefully.
The dosing curve.
Standard titration: 0.25 mg weekly for 4 weeks, then 0.5, 1.0, 1.7, 2.4 mg, advancing every 4 weeks if tolerated. Most GI side effects (nausea, constipation, reflux) occur during titration and resolve at the maintenance dose for most patients.
Compounded semaglutide from telehealth platforms is a dose-and-purity question. The active ingredient is real, but third-party potency testing is variable. Brand-name product, when affordable, is the safest path.
What happens when you stop.
In trials, two-thirds of weight lost is regained within one year of stopping. This is biological, not behavioral — appetite hormones return to baseline. The honest framing: GLP-1 is chronic medication for a chronic condition, like statins or antihypertensives.
Some clinicians use a tapering protocol with gradual lifestyle reinforcement. Long-term retention data for tapering is preliminary. Plan for chronic therapy or accept partial regain — those are the two realistic pathways.
Common questions.
Is it safe long-term?
Semaglutide has been in use since 2017 (diabetes) and 2021 (obesity). Long-term safety beyond 5 years is extrapolated from related GLP-1 agonists with longer track records. The signal so far is favorable; rare adverse events (pancreatitis, gallstones) occur at low rates.
Will I lose muscle?
Weight loss from any cause produces some lean mass loss. Resistance training and adequate protein (1.2–1.6 g/kg/day) attenuate it substantially. Without those, lean mass loss can reach 25–40% of total weight lost — clinically significant.
What about 'Ozempic face'?
Rapid weight loss reduces facial fat pad volume, producing a hollowed look. This is not specific to GLP-1 — it happens with any rapid loss. Slower weight loss, hydration, and selective filler can address it if it occurs.
Compounded vs branded — what's the difference?
Compounded semaglutide is mixed by 503A/503B pharmacies, often with B12 or other additions. Cost is lower ($200–$400/month vs $1,000+ for Wegovy). Quality variance is the trade-off. As of 2025, the FDA shortage list ended; compounding may face increasing regulatory pressure.
Tirzepatide vs semaglutide?
Tirzepatide (Mounjaro/Zepbound) is a dual GIP/GLP-1 agonist with stronger weight-loss efficacy in head-to-head trials (~20% vs ~15%). Side effect profiles are similar. Choice often comes down to insurance coverage and individual response.
Can I drink alcohol?
Many patients report dramatic reduction in alcohol cravings on GLP-1, an effect now being studied for alcohol use disorder. Drinking is not contraindicated but tolerance and pleasure both decrease for most people.