Pharmacology · GLP-1 receptor agonists
Semaglutide !
A long-acting GLP-1 agonist, weekly by injection or daily by mouth: strong glucose lowering, large weight loss and fewer cardiovascular events.
Updated 2026-11-01
The figure shows semaglutide bound to the human GLP-1 receptor coupled to its Gs protein; the nanobody used to stabilize the complex is not part of the receptor.
Mechanism of action
Semaglutide is a GLP-1 analogue with an amino-acid change that blocks DPP-4 and a long fatty diacid chain that binds albumin strongly, giving a week-long action. On the GLP-1 receptor it increases glucose-dependent insulin release, lowers glucagon, slows gastric emptying and acts on appetite centers in the brain, which explains its large effect on weight.
- Activates the GLP-1 receptor (Gs, cAMP)
- Beta cells release more insulin when glucose is high
- Glucagon falls and the stomach empties more slowly
- Appetite falls: lower glucose and weight
Pharmacokinetics
- Absorption
- Weekly subcutaneous injection; the oral tablet is absorbed in the stomach with the help of an absorption enhancer and needs an empty stomach.
- Distribution
- Almost entirely bound to albumin.
- Metabolism
- Broken down by peptidases and fatty-acid oxidation.
- Half-life
- Long, which allows once-weekly injection.
Indications
- Type 2 diabetes, and to reduce heart attack, stroke and death in those with cardiovascular disease Type 2 diabetes mellitus →
- Chronic weight management in obesity or overweight with weight-related conditions Obesity →
- Type 2 diabetes with chronic kidney disease, to slow kidney decline Chronic kidney disease →
Adverse effects
Common
- Nausea, vomiting, diarrhea, constipation, abdominal pain (most common, mostly at the start)
- Reduced appetite
- Injection-site reactions
- Slightly faster heart rate
Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia type 2 (MEN 2)
- Serious hypersensitivity to the drug
Key interactions
- Insulin or sulfonylureas
- Higher risk of hypoglycemia; their dose is often reduced.
- Oral drugs in general
- Slower gastric emptying can change their absorption.
What is monitored
- HbA1c and weight
- Eye exams in people with diabetic retinopathy
- Kidney function if vomiting or diarrhea
- Symptoms of pancreatitis or gallbladder disease
Administration and safety
- Subcutaneous injection in the abdomen, thigh or upper arm, rotating sites.
- Pens are for one person only and are never shared, even with a new needle.
- The dose is raised step by step to limit nausea.
- The oral tablet is taken on an empty stomach with a little water, waiting before eating or other medicines.
Nursing care
- Before: thyroid history (medullary carcinoma, MEN 2), pancreatitis history, kidney function.
- During: severe abdominal pain spreading to the back (pancreatitis), vomiting and dehydration.
- Teach to report a neck lump, hoarseness or trouble swallowing.
- The anesthesia team is told before surgery or endoscopy.
Pregnancy and breastfeeding
Not used in pregnancy (weight loss is not a goal and animal data showed harm); it is stopped ahead of a planned pregnancy.
Test yourself
Think of the answer, then tap the question to see it.
What makes semaglutide last about a week?
A fatty diacid chain that binds albumin tightly, plus an amino-acid change that blocks DPP-4.
Which eye problem can worsen when semaglutide lowers glucose quickly?
Diabetic retinopathy; people who already have it need eye follow-up.
Before a semaglutide user has elective surgery, why should the anesthesia team know?
The drug slows gastric emptying, so the stomach may not be empty and the risk of aspiration rises.
Which two benefits beyond glucose lowering has semaglutide shown?
Weight loss and fewer major cardiovascular events (heart attack, stroke, cardiovascular death) in people with cardiovascular disease; also slower kidney decline in diabetic kidney disease.
Related drugs
Related conditions
← Back to the class: GLP-1 receptor agonists
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Semaglutide Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Semaglutide-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in Complex with Gs protein (RCSB Protein Data Bank, 2021); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.