Semaglutide is a synthetic peptide drug of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class. It is developed and marketed mainly by Novo Nordisk. It is used to improve blood glucose control in type 2 diabetes, to treat obesity, and, in selected adults, to reduce the risk of major adverse cardiovascular events. Several brands exist, including Ozempic, Wegovy and Rybelsus, which differ in indication, dose and route of administration.
Chemistry and pharmacokinetics
Semaglutide is an analogue of the human hormone GLP-1, which is released from the intestine after eating. The peptide has about 94% sequence homology with native GLP-1. Three structural changes make it more stable than the natural hormone. One change protects it from the enzyme DPP-4, which otherwise breaks GLP-1 down quickly. A C-18 fatty diacid chain attached through a linker lets the molecule bind serum albumin. Albumin binding reduces renal clearance and slows enzymatic breakdown. As a result, the half-life is roughly one week, which allows once-weekly subcutaneous dosing.
Mechanism of action
Semaglutide binds to and activates the GLP-1 receptor, a class B G-protein-coupled receptor. The receptor is expressed in the pancreas, brain, heart, gut and adipose tissue. In the pancreas, activation raises intracellular cyclic AMP in beta cells, which increases insulin secretion in a glucose-dependent way. Glucagon secretion is reduced when glucose is high. Because insulin release depends on glucose levels, the risk of hypoglycemia is lower than with agents that stimulate insulin regardless of glucose. Gastric emptying is slowed slightly in the early postprandial period.
Weight loss cannot be explained by slowed gastric emptying alone. Preclinical and neuroimaging studies point to direct action on appetite-regulating circuits in the hypothalamus and brainstem, and to effects on reward-related dopamine signalling. Human data on the exact pathways remain incomplete. Proposed explanations for cardiovascular and metabolic benefit include reduced inflammation and reduced atherosclerotic progression, although the relative contribution of each mechanism is not firmly established.
Formulations and approved uses
Semaglutide is given in several products, which differ in dose and indication:
- Ozempic is an injectable product approved for type 2 diabetes. It is also used off-label for weight loss at a prescriber's discretion.
- Wegovy is an injectable product approved for chronic weight management in adults with obesity, or with overweight accompanied by weight-related medical problems. It is also approved for reducing cardiovascular risk in people with established cardiovascular disease and obesity or overweight, and for the liver condition metabolic dysfunction-associated steatohepatitis in adults with moderate to advanced fibrosis.
- Rybelsus is an oral tablet approved for type 2 diabetes. It was the first oral GLP-1 medicine on the market, and it is not approved for weight management.
- Oral Wegovy is a 25 mg once-daily tablet. The U.S. Food and Drug Administration approved it on 22 December 2025, as the first oral GLP-1 therapy for chronic weight management. The tablet is formulated with the absorption enhancer SNAC, which temporarily raises gastric pH and assists absorption across the stomach lining.
Not all of these indications are available in every country. Regulatory status varies by jurisdiction and changes over time.
Clinical evidence
Glycaemic control and weight
Phase 3 trials in the STEP programme showed substantial weight loss with the 2.4 mg weekly injection, and the oral formulation showed similar effects in its own trials. In the 64-week OASIS 4 trial of the oral 25 mg tablet, results depended on the analysis. Sources report about 17% average weight loss in participants who stayed on treatment, and about 14% when all randomised participants are counted regardless of adherence. Weight loss plateaus with continued treatment, and weight tends to return after discontinuation.
Cardiovascular outcomes
The SELECT trial, in people with overweight or obesity and established cardiovascular disease but without diabetes, showed a reduction in major adverse cardiovascular events. This finding is the basis for the cardiovascular indication of the injectable 2.4 mg product.
Alzheimer's disease
Observational data and some trials in people with diabetes suggested a lower risk of dementia among users of GLP-1 drugs. The phase 3 EVOKE and EVOKE+ trials tested oral semaglutide 14 mg in about 3,800 people with early symptomatic Alzheimer's disease. Both trials were negative. Participants showed reductions in inflammatory and some cerebrospinal fluid biomarkers, including high-sensitivity C-reactive protein, but no slowing of cognitive and functional decline on the Clinical Dementia Rating scale. The trial extension was discontinued. These results have been discussed as evidence that reducing peripheral inflammation may be insufficient to change the clinical course of established Alzheimer's disease.
Adverse effects and safety
The most common adverse reactions are gastrointestinal: nausea, diarrhoea and vomiting, which are most frequent during dose escalation. Other reported effects include constipation, abdominal discomfort and gallbladder disease, including gallstones. Pancreatitis has been reported, and the product labelling carries warnings about thyroid C-cell tumours seen in rodents. Retinal complications, acute kidney injury caused by dehydration from gastrointestinal losses, and suicidal ideation have also been examined in regulatory reviews, with varying conclusions. Semaglutide is contraindicated in people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Long-term safety data are still accumulating.
Access, cost and market
Demand for semaglutide has been very high since the early 2020s, and supply shortages were reported for some products. Prices and reimbursement differ widely between countries and insurers. Compounded semaglutide, produced by licensed compounding pharmacies, has been sold as a lower-cost alternative. The U.S. Food and Drug Administration has said that compounded products are not approved or evaluated for safety, efficacy or quality, and that they are not finished products of the approved drug.
Patent protection for the core molecule is expected to expire in several large markets around 2026, which is expected to allow generic and biosimilar-type competition in those markets. Timing differs by country, and it depends on the outcome of patent litigation and on regulatory approval of generic versions.
Limitations and controversies
Several issues remain under discussion. The first is the durability of benefit. Weight regain after stopping treatment is common, which suggests that many patients need long-term therapy. The second is the gap between surrogate and clinical endpoints, illustrated by the EVOKE results. The third is access and equity, because high prices and supply constraints limit use in many health systems, and because the drugs have been used off-label and in cosmetic contexts. The fourth is the extent of weight loss in real-world populations compared with trial populations, where adherence and dosing differ. Ongoing research addresses long-term safety, the effects of combination therapies, and other indications, including kidney disease and sleep apnoea.
References
- Semaglutide: Uses, Interactions, Mechanism of Actiongo.drugbank.com
- pharos.nih.govpharos.nih.gov
- Mechanism of Actionnovomedlink.com
- GLP-1 Receptor Agonists Best Price: Mechanisms of Action and Class Overviewusobesityscience.org
- What is the mechanism of action of Semaglutide?synapse.patsnap.com
- Spotlight on the Mechanism of Action of Semaglutide - PMCpmc.ncbi.nlm.nih.gov
- GLP-1 receptor agonist semaglutide reduces appetite while increasing dopamine reward signaling - ScienceDirectsciencedirect.com
- Best Semaglutide Options for 2026: New Oral Wegovy Pill Approved by FDA as Patients Compare Injectable and Compounded Access Pathways - BioSpacebiospace.com
- FDA Approves Semaglutide (Wegovy) Pill As First Oral GLP-1 for Weight Losshcplive.com
- FDA Approves Novo Nordisk’s Wegovy Pill, Marking First Oral GLP-1 for Weight Managementpharmaceuticalcommerce.com
- Wegovy Pill: What to Know About Oral Wegovy for Weight Lossro.co
- Wegovy Pill: What to Know About the FDA-Approved Oral Optionskinnyrx.com
- GLP-1 Semaglutide Fails to Outperform Placebo in Phase 3 EVOKE Trial of Alzheimer Diseaseneurologylive.com
- CTAD Presentation Lays Insights Into Disappointing Phase 3 EVOKE Trial of GLP-1 Semaglutide in Alzheimer Diseaseneurologylive.com
- Results of EVOKE and EVOKE+ trials show no effect of oral semaglutide on AD progressionalzheimer-europe.org
- Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials - The Lancetthelancet.com
- Evoke (+) trials of semaglutide for early alzheimer’s disease: Innovations, lessons, and implications - ScienceDirectsciencedirect.com
- Semaglutide for Alzheimer’s Disease: What the EVOKE Trials Taught Usmedscape.com
- Semaglutide Fails to Slow Cognitive Decline in Early Alzheimer’s: Phase 3 Datamedscape.com