Drug facts

How semaglutide works

Quick answer

It imitates GLP-1, a hormone the gut releases after eating — one receptor, where tirzepatide acts on two. That single action slows the stomach, signals fullness, and prompts insulin release when blood sugar is high.

One receptor1

Semaglutide is a GLP-1 receptor agonist: a molecule shaped closely enough to glucagon-like peptide-1 to bind the same receptor, and engineered to last far longer than the natural hormone, which is broken down within minutes.

That “one” is the honest point of difference from tirzepatide, which adds a GIP receptor. Whether two is better than one for any given person is not a question a mechanism answers — it is what the head-to-head trials were for.

What that produces2

Three effects that all follow from the same binding. Gastric emptying slows, so food stays in the stomach longer. Appetite and energy intake fall. And insulin secretion rises in a glucose-dependent way — meaning it responds when blood sugar is high, which is why the drug alone is much less likely to cause hypoglycemia than insulin is.

The side effects are the same mechanism2

This is the part worth carrying away. Constipation, nausea and fullness are not a separate malfunction sitting alongside the benefit — they are the delayed gastric emptying that produces the benefit. So is the anesthesia warning, and so is the caution about oral medicines.

Why it is weekly1

Because it was designed to resist the enzyme that clears natural GLP-1 and to bind to albumin in the blood, which keeps it circulating for days rather than minutes. The same long half-life is why the label asks for discontinuation two months before a planned pregnancy, and why a missed dose is judged against the next one rather than the last. What the first weeks on it look like in the trials is on how long semaglutide takes to work.

Sources

  1. FDA prescribing information for WEGOVY (semaglutide), section 12.1 Mechanism of Action, revision 6/2026 DailyMed
  2. FDA prescribing information for WEGOVY (semaglutide), section 12.2 Pharmacodynamics, revision 6/2026 DailyMed