★ Metabolic

Semaglutide

Metabolic · 5mg × 10 vials

The foundational once-weekly GLP-1 agonist. Studied for satiety signaling and glycemic control.

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Overview

What Is Semaglutide?

Semaglutide is a long-acting analogue of the gut hormone GLP-1 (glucagon-like peptide-1) and a selective GLP-1 receptor agonist. An albumin-binding fatty-acid side chain extends its half-life to about seven days, against hours for the earlier analogue liraglutide. It activates GLP-1R at three sites: the pancreas (glucose-dependent insulin release and glucagon suppression), the gut (slowed gastric emptying), and the brain (the arcuate nucleus and brainstem appetite centres).

The net effect in the trial literature is reduced caloric intake, delayed gastric emptying, and improved glycaemic control. Unlike tirzepatide (dual GLP-1/GIP) and retatrutide (triple GLP-1/GIP/glucagon), semaglutide acts on a single receptor, which gives it the longest safety record and the most extensively characterised response of the class, alongside smaller weight reductions than the dual and triple agonists in head-to-head trials. In the STEP 1 trial, participants lost a mean of 14.9% of body weight at 68 weeks. Semaglutide is approved as Ozempic (type 2 diabetes), Wegovy (chronic weight management), and Rybelsus (an oral formulation).

Published Safety Data

What the published studies measured.

What the studies show

Measured in clinical trials

Nausea: 44% at 2.4 mg (STEP-1) vs 16% placebo - mild to moderate, peaks during titration weeks 4-12, resolves by week 16-20 for most subjects
Diarrhea: 31% at 2.4 mg vs 16% placebo - mild to moderate
Vomiting: 24% at 2.4 mg vs 6% placebo - mostly at titration steps, peaks at 1.0 → 1.7 mg jump
Constipation: 24% at 2.4 mg vs 11% placebo - generally mild but persistent, often requires fiber + magnesium intervention
Abdominal pain: 20% at 2.4 mg vs 10% placebo
Headache: 14% at 2.4 mg vs 11% placebo
Fatigue: 11% at 2.4 mg vs 5% placebo
Gallbladder events (cholelithiasis, cholecystitis): 2.6% vs 1.2% placebo (STEP-1) - elevated risk with rapid weight loss, not unique to sema, applies to all GLP-1 class

The Research

Peer-reviewed studies and clinical guidelines - tap any to read the source.

PubMed / NEJMWilding et al., NEJM 2021 - STEP-1 trial

pivotal obesity efficacy, 1961 pts, 68 weeks, 14.9% mean weight loss at 2.4 mg

Read study ↗PubMed / LancetDavies et al., Lancet 2021 - STEP-2 trial

00213-0/abstract) - T2D + obesity, semaglutide 2.4 mg outperformed both 1.0 mg and placebo for weight management

Read study ↗PubMed / Nature MedicineGarvey et al., Nature Med 2022 - STEP-5 trial 2-year data

sustained 15.2% loss at 104 weeks, no tapering of effect

Read study ↗PubMed / JAMARubino et al., JAMA 2022 - STEP-8 head-to-head vs liraglutide

sema 15.8% vs lira 6.4% at 68 weeks, sema 6.3× more likely to hit 10% loss

Read study ↗PubMed / NEJMWadden et al., JAMA 2021 - STEP-3 intensive behavioral therapy

16.0% weight loss with sema + IBT vs 5.7% IBT alone