Semaglutide
GLP-1 receptor agonist (Ozempic, Wegovy)
Semaglutide is a once-weekly GLP-1 receptor agonist that lowers appetite and blood sugar. It is FDA-approved for type 2 diabetes (Ozempic) and chronic weight management (Wegovy), backed by large phase 3 trials. In the main Wegovy trial, adults on 2.4 mg weekly lost an average of 14.9% of body weight over 68 weeks.
Quick reference
How Semaglutide is dosed in practice
Wegovy (weight management) follows the FDA label: 0.25 mg once a week for 4 weeks, then 0.5 mg, 1 mg and 1.7 mg for 4 weeks each, reaching the 2.4 mg maintenance dose at week 17. The low early doses are for getting used to the drug, not for weight loss.
Ozempic (type 2 diabetes) starts the same way — 0.25 mg weekly for 4 weeks, then 0.5 mg — and can be increased to 1 mg and then 2 mg, each after at least 4 weeks at the previous dose, if blood sugar needs more control.
Inject once a week on the same day, at any time of day, with or without food. If side effects are hard to tolerate, prescribers often delay the next step rather than push through.
Where the numbers come from: the FDA labels and the phase 3 trials behind them. This guide does not list doses above the labeled maximums.
Work out the units to draw with the reconstitution calculator and how long a vial lasts with the vial duration calculator.
How Semaglutide works
Semaglutide activates the GLP-1 receptor in the pancreas (glucose-dependent insulin release), in the brain's appetite centers (less hunger and 'food noise'), and in the gut (slower stomach emptying, so you feel full longer). It is not a stimulant; it amplifies the body's own after-meal fullness signals.
A fatty-acid side chain binds albumin in the blood and slows clearance, giving a half-life of about a week. That is why semaglutide is weekly while liraglutide (Saxenda, Victoza) is daily.
Most people describe the effect as appetite normalization — fewer cravings and less 'food noise' — rather than forced restriction.
In the DoseCraft framework, semaglutide addresses Insulin Resistance (better blood-sugar control) and Inflammation (inflammation markers such as C-reactive protein fell in trials).
Safety + side-effect profile
Stomach and bowel side effects are the main problem, mostly during dose increases. They often ease after a few weeks at each dose — slow titration matters more than pushing to the next step.
Boxed warning: semaglutide caused thyroid C-cell tumors in rodents; whether it does in humans is unknown. Don't use it if you or a family member has had medullary thyroid carcinoma (MTC), or if you have MEN 2. Other label warnings: pancreatitis, gallbladder problems, low blood sugar when combined with insulin or sulfonylureas, kidney problems from dehydration, and diabetic eye (retinopathy) complications in people with type 2 diabetes. Pregnancy: stop at least 2 months before a planned pregnancy.
Interactions: don't combine with another GLP-1 drug (tirzepatide, liraglutide, retatrutide) — they act on the same receptor and the combination hasn't been studied. With insulin or sulfonylureas, the dose of those drugs often needs to come down to avoid low blood sugar. Slower stomach emptying can change how some oral medicines are absorbed.
Lean mass: part of the weight lost on semaglutide is muscle and other lean tissue, not just fat. Resistance training and enough protein are the standard advice to limit this.
- • Nausea (the most common side effect; reported by about 4 in 10 people in the Wegovy trials, mostly during dose increases)
- • Diarrhea, constipation or vomiting
- • Reflux / heartburn (especially with large meals)
- • Fatigue in the first weeks
- • Less 'food noise' (intended effect)
- • Less interest in alcohol (reported by some; not an approved use)
Frequently asked
What is Semaglutide?
Semaglutide is a once-weekly GLP-1 receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, 2017) and chronic weight management (Wegovy, 2021). It lowers appetite, slows stomach emptying and improves blood-sugar control.
What is the standard Semaglutide titration?
Per the Wegovy label: 0.25 mg weekly for 4 weeks → 0.5 mg for 4 weeks → 1 mg for 4 weeks → 1.7 mg for 4 weeks → 2.4 mg weekly maintenance from week 17. For type 2 diabetes (Ozempic), the usual target is 0.5–2 mg weekly, increasing only after at least 4 weeks on each dose. If side effects are hard to tolerate, prescribers often delay the next step.
Should I stack Semaglutide with Tirzepatide or Retatrutide?
No. Tirzepatide also activates the GLP-1 receptor (plus GIP), and retatrutide activates GLP-1, GIP and glucagon receptors. Combining them hasn't been studied and would be expected to add side effects — pick one. In a head-to-head trial in adults with obesity, tirzepatide produced more weight loss than semaglutide; retatrutide is still investigational and not FDA-approved.
How fast will I lose weight on Semaglutide?
In the main Wegovy trial (STEP 1), adults on 2.4 mg weekly lost an average of 14.9% of body weight over 68 weeks, compared with 2.4% on placebo. Weight loss is gradual and varies between people. Very fast loss raises the risk of gallbladder problems and lean-mass loss.
How do I preserve lean mass on Semaglutide?
Part of the weight lost on semaglutide is lean tissue, including muscle. Regular resistance training and enough protein are the standard advice to protect it; a dietitian or clinician can help you set a protein target.
Can I drink alcohol on Semaglutide?
Alcohol isn't prohibited. Some people report less interest in drinking; this is being studied but isn't an approved use. Alcohol can make nausea worse, and if you take insulin or a sulfonylurea it raises the risk of low blood sugar.
What happens when I stop Semaglutide?
Weight regain is common. In the STEP 1 extension, people regained about two-thirds of the weight they had lost within a year of stopping. There's no tested tapering schedule; plan any stop with your prescriber and keep the training and eating habits that help maintain weight.
Are there long-term safety concerns?
Semaglutide has been on the market since 2017, and large trials have followed people for years, including a heart-outcomes trial in type 2 diabetes. Known risks include pancreatitis, gallbladder problems and the boxed warning about thyroid C-cell tumors in rodents (avoid with a personal or family history of MTC or with MEN 2). It is meant for long-term use under medical supervision.
Protocols using Semaglutide
Outcome-driven stacks with phased dose schedules and cited PMIDs.
Head-to-head comparisons
Cited side-by-side breakdowns that include Semaglutide.
Related compounds
Often researched, stacked, or compared with Semaglutide.
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