Semaglutide

How it works

Semaglutide is a long-acting copy of glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone your gut makes after you eat. Semaglutide acts on GLP-1 receptors in three places. In the pancreas, it helps release insulin when your blood sugar is high. In the gut, it slows how fast food leaves your stomach. In the parts of the brain that control hunger, it turns down hunger and 'food noise'.

The evidence

The STEP 1 trial (2021, NEJM) studied adults without diabetes on weekly brand-name semaglutide (Wegovy) 2.4 mg. After 68 weeks, they lost ~14.9% of their body weight on average. People on placebo lost ~2.4%. The SELECT trial (2023) studied people with overweight or obesity who already had heart disease. Wegovy cut major heart events, like heart attack and stroke, by 20%. These trials studied the FDA-approved brand-name products that contain this molecule (Wegovy, Ozempic). The results apply to those products only.

Typical dosing

The dose goes up slowly. This is called titration. You start with a 0.25 mg shot under the skin once a week for 4 weeks. Then the dose steps up every 4 weeks (0.5 → 1.0 → 1.7 → 2.4 mg), as long as your body handles it. The maintenance dose is usually between 1.0 mg and 2.4 mg a week.

Side effects

Common

Nausea
Constipation
Diarrhea
Tiredness (early on, while the dose goes up)
Less appetite

Less common

Acid reflux
Reactions where you inject
Gallbladder discomfort

Rare

Pancreatitis (swelling of the pancreas)
Sudden kidney injury (linked to dehydration)

Drug interactions

Insulin and sulfonylureas: higher risk of low blood sugar. Their doses may need to be lowered
Pills that need very exact dosing (a narrow therapeutic window): absorbed more slowly, because your stomach empties more slowly
GLP-1 / GIP medicines like tirzepatide: never take them together

Frequently asked

Which products contain semaglutide?

Semaglutide is the active molecule in several FDA-approved products. They are Ozempic (for type 2 diabetes), Wegovy (for chronic weight management), and Rybelsus (a pill). Compounded semaglutide is made by 503A pharmacies. It is not FDA-approved, and it is not an FDA-approved generic or equivalent of those brand-name products.

How long until results?

Hunger starts to drop within 1–2 weeks. Weight usually starts to change around week 4–8, as the dose goes up on schedule.

Can I stop and restart?

Yes, but plan it around your dose schedule. If you restart at your full dose after a long break, you'll get the same side effects you had when you first started.