Semaglutide
Also referenced as: Ozempic, Wegovy, Rybelsus, GLP-1 receptor agonist
A long-acting GLP-1 receptor agonist and the most heavily studied peptide in modern metabolic medicine.
- Evidence grade
- AStrong Clinical Evidence
Strong Clinical Evidence
- Regulatory status
- FDA Approved for Specific Indication
Approved in the United States for type 2 diabetes and, at a higher dose as Wegovy, for chronic weight management with additional cardiovascular indications. Use outside an approved indication, or from a research-use-only source, is not an approved medical use.
- Human data
- Yes
Registered clinical trials exist
- Last reviewed
- September 1, 2026
Overview
Semaglutide is a synthetic analogue of glucagon-like peptide-1 (GLP-1), a hormone the gut releases after eating. Structural changes to the natural hormone make semaglutide resistant to rapid breakdown, so a single weekly injection maintains activity where the natural hormone lasts minutes.
It is one of the few compounds discussed in peptide circles that has passed through the full drug development pathway: large phase 3 programmes, published outcome trials, regulatory review and marketed prescribing labels.
Why It's Being Studied
- Glycaemic control in type 2 diabetes, where GLP-1 signalling increases glucose-dependent insulin release.
- Appetite regulation and body weight, through central effects on satiety and slowed gastric emptying.
- Cardiovascular and kidney outcomes in people with excess weight or diabetes.
- Emerging questions about inflammation, liver fat and addictive behaviour, which remain far less settled.
Mechanism of Action
Semaglutide mimics a natural gut hormone that tells the pancreas to release insulin when blood sugar is high and tells the brain that a meal has been eaten.
Semaglutide is an acylated GLP-1 analogue with an aminoisobutyric acid substitution at position 8 and a C18 fatty diacid side chain, giving strong albumin binding and resistance to dipeptidyl peptidase-4 cleavage. Agonism at the GLP-1 receptor raises intracellular cAMP in pancreatic beta cells, potentiating glucose-dependent insulin secretion while suppressing glucagon. Central GLP-1 receptor populations in the hypothalamus and area postrema mediate reduced energy intake; peripheral effects include delayed gastric emptying.
Research Areas & Routes Studied
- Glycaemic control
- Body weight
- Cardiovascular outcomes
- Kidney outcomes
- Hepatic steatosis
- Subcutaneous injection
- Oral tablet (approved form)
Evidence Summary
Multiple large, randomised, placebo-controlled phase 3 trials in humans, plus cardiovascular outcome trials and approved prescribing labels in several indications.
Human clinical evidence
- The STEP programme reported substantial mean weight reduction versus placebo over 68 weeks in adults with overweight or obesity, alongside lifestyle intervention.
- The SUSTAIN programme reported HbA1c reductions in type 2 diabetes across comparators.
Clinical trials
- Dozens of registered interventional trials continue in cardiometabolic, hepatic and neurological indications.
Observational evidence
- Large real-world cohorts broadly reproduce trial-level weight and glycaemic effects, with higher discontinuation rates than trials.
Animal studies
- Rodent studies established the central appetite mechanism and remain the basis for several open mechanistic questions.
Anecdotal / community information
- Community reports circulate widely about compounded and research-use-only material of unverified identity and purity. These are not evidence about the approved medicine.
Reported Adverse Events in Research
- Nausea, vomiting, diarrhoea and constipation are the most frequently reported effects in trials.
- Gallbladder events and pancreatitis have been reported; labels carry specific warnings.
- A boxed warning for thyroid C-cell tumours appears on US labels, based on rodent findings.
- Loss of lean mass and nutritional adequacy during rapid weight loss are active research questions.
Limitations of Current Evidence
- Trial populations were largely enrolled with lifestyle support that real-world users may not receive.
- Weight regain after discontinuation has been documented in extension studies.
- Long-term data beyond several years remain limited relative to the scale of current use.
Documented Research Protocols
Semaglutide 2.4 mg weekly — approved escalation schedule
Summarise the dose-escalation schedule established by the approved prescribing label and the STEP phase 3 programme for chronic weight management.
View documented protocol
Why It Is Used
- Metabolic Health
Weight Loss and Liver Fat
The most common reason people look at peptides at all: sustained appetite reduction, and what trials report about liver fat alongside it.
Read the case study
Research References
- Randomised controlled trial2021
Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
Wilding JPH, et al. · New England Journal of Medicine- Population
- 1,961 adults with BMI ≥30 (or ≥27 with comorbidity)
- Main finding
- Mean body weight change of about −14.9% with semaglutide 2.4 mg versus −2.4% with placebo at week 68.
- Limitations
- Lifestyle counselling in both arms; participants were predominantly female and white.
- Randomised controlled trial2023
Semaglutide and Cardiovascular Outcomes in Obesity (SELECT)
Lincoff AM, et al. · New England Journal of Medicine- Population
- Adults with overweight or obesity and established cardiovascular disease, without diabetes
- Main finding
- Lower incidence of major adverse cardiovascular events versus placebo.
- Limitations
- Secondary-prevention population; not a primary-prevention result.
- Prescribing label
Semaglutide prescribing information
- Main finding
- Approved indications, dose escalation schedule, contraindications and boxed warning.
- Regulatory document
Registered semaglutide trials