---
title: "How Does Semaglutide Work? The GLP-1 Receptor"
url: https://www.primaralabs.com/answers/how-does-semaglutide-work
source: Primara Labs, markdown mirror of the HTML page
---

# How does semaglutide work?

Semaglutide is a modified form of the gut hormone GLP-1 that binds and activates the GLP-1 receptor, and only that receptor. As of 23 September 2026 it is the active ingredient in US-approved prescription medicines, studied in the STEP weight trials and in SELECT, a cardiovascular outcomes trial of 17,604 people.

Primara Labs sells some of the compounds covered here. Every figure on this page links to its source and the date it was checked.

Updated 23 September 2026

01

## One receptor

Semaglutide is a GLP-1 analogue that selectively binds to and activates the GLP-1 receptor, the target of native GLP-1.

Native GLP-1 lasts minutes in the blood; semaglutide is modified so that it lasts far longer, which is what allows weekly use in the approved medicines. Tirzepatide adds GIP receptor activity and retatrutide adds glucagon as well.

02

## What the trials measured

In STEP 1, a phase 3 trial of semaglutide in adults with BMI of 30 or greater (27 or greater with at least one weight-related coexisting condition), without diabetes (n=1,961), mean body weight fell 14.9% on 2.4 mg over 68 weeks, against 2.4% on placebo (treatment-policy estimand; Wilding JPH et al. N Engl J Med 2021;384:989-1002).

In SELECT, a phase 3 trial of semaglutide in patients 45 years or older with preexisting cardiovascular disease and BMI of 27 or greater, no history of diabetes (n=17,604), the primary endpoint, death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke, occurred in 6.5% on semaglutide against 8.0% on placebo, a hazard ratio of 0.80 (95% CI 0.72 to 0.90) (Lincoff AM et al. N Engl J Med 2023 (SELECT)).

03

## Adverse events

In STEP 3, discontinuation because of adverse events was 5.9% on 2.4 mg, against 2.9% on placebo. The most frequently reported adverse events were gastrointestinal adverse events in 82.8% on 2.4 mg against 63.2% on placebo, nausea in 58.2% on 2.4 mg against 22.1% on placebo, constipation in 36.9% on 2.4 mg against 24.5% on placebo and diarrhoea in 36.1% on 2.4 mg against 22.1% on placebo.

Sources

## Where every figure comes from

1.  [Semaglutide mechanism source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42bdd912-2393-44c4-b7e0-47672ca28991) · checked 23 September 2026
2.  [Wilding JPH et al. N Engl J Med 2021;384:989-1002](https://doi.org/10.1056/NEJMoa2032183) · checked 23 September 2026
3.  [Lincoff AM et al. N Engl J Med 2023 (SELECT)](https://doi.org/10.1056/NEJMoa2307563) · checked 23 September 2026

Last reviewed 23 September 2026

Read next

## Related pages

-   [Semaglutide 15mg](https://www.primaralabs.com/marketplace/semaglutide-15mg)
-   [SELECT on the Trial Explorer](https://www.primaralabs.com/research/trials/select)
-   [Tirzepatide vs semaglutide: trial data](https://www.primaralabs.com/research/compare/tirzepatide-vs-semaglutide)

-   [What are the side effects of semaglutide?](https://www.primaralabs.com/answers/what-are-the-side-effects-of-semaglutide)
-   [Is semaglutide approved in the Philippines?](https://www.primaralabs.com/answers/is-semaglutide-approved-in-the-philippines)