Semaglutide

The most-prescribed GLP-1 for weight management. Produces roughly 15% average body-weight loss in trials and is the reference molecule against which newer options are measured.

What semaglutide is Semaglutide is a synthetic analog of GLP-1 (glucagon-like peptide-1), a gut hormone released after eating. It binds the same receptors as natural GLP-1 but resists breakdown, so one dose keeps working for about a week. It slows stomach emptying, blunts appetite signaling in the brain, and improves insulin response — the combined effect is that people feel full sooner, think about food less, and eat substantially less without white-knuckle willpower. ## The evidence Semaglutide has the deepest evidence base of any modern weight-loss medication: - STEP 1 trial (NEJM, 2021): adults without diabetes on 2.4 mg weekly lost an average of 14.9% of body weight over 68 weeks, versus 2.4% on placebo. - STEP 5: weight loss was sustained through two years of continuous use. - SELECT trial (2023): in adults with cardiovascular disease and overweight/obesity, semaglutide 2.4 mg cut the risk of major cardiovascular events (heart attack, stroke, CV death) by 20% — the first weight-loss drug ever to show this. ## Forms you will encounter | Form | What it is | FDA-approved? | | --- | --- | --- | | Wegovy | Brand pen, 2.4 mg target dose, approved for weight management | Yes | | Ozempic | Brand pen, approved for type 2 diabetes (often used off-label for weight) | Yes | | Rybelsus | Daily oral tablet, approved for type 2 diabetes | Yes | | Compounded injectable | Pharmacy-prepared vials/syringes, prescribed when a clinician documents need for a customized formulation | No | | Sublingual / rapid-dissolve | Under-the-tongue compounded form; different absorption, not dose-equivalent to injections | No | ## Side effects in brief Mostly gastrointestinal and front-loaded during dose increases: nausea (the most common), constipation, diarrhea, fatigue. Serious but rare risks include pancreatitis and gallbladder disease. Semaglutide carries a boxed warning about thyroid C-cell tumors seen in rodents; it is contraindicated with personal/family history of medullary thyroid carcinoma or MEN 2, and in pregnancy. See the side-effects guide for management strategies. ## Cost reality List price for Wegovy is roughly $1,350/month, but almost nobody pays that: manufacturer direct-pharmacy programs offer it for around $499/month cash, insurance copays vary widely, and compounded semaglutide typically runs $199–$399/month. The cost guide walks through every option.