Also known as: Ozempic, Wegovy, Rybelsus
Half-life: ~7 days (168 hours)
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the incretin hormone GLP-1, which is naturally released from the gut after eating. It works by binding to GLP-1 receptors in the pancreas to stimulate insulin secretion, suppress glucagon release, slow gastric emptying, and reduce appetite through central nervous system signaling. Engineered with a C-18 fatty diacid chain that enables albumin binding, semaglutide has a half-life of approximately one week, allowing for convenient once-weekly dosing.
Originally developed and approved for type 2 diabetes management (Ozempic, 2017), semaglutide gained massive public attention when higher-dose formulations demonstrated unprecedented weight loss in clinical trials. The STEP trial program showed that 2.4 mg weekly semaglutide (Wegovy) produced average weight loss of approximately 15-17% of body weight over 68 weeks in non-diabetic individuals with obesity. An oral formulation (Rybelsus) was also approved in 2019, becoming the first oral GLP-1 receptor agonist available.
Beyond metabolic effects, semaglutide has shown cardiovascular benefits. The landmark SELECT trial (2023) demonstrated a 20% reduction in major adverse cardiovascular events in overweight or obese adults without diabetes, expanding the clinical significance of the drug well beyond glucose control and weight management. Semaglutide has fundamentally shifted the obesity treatment landscape and sparked enormous interest in GLP-1 based therapies.
Semaglutide was developed by Novo Nordisk, building on their extensive experience with GLP-1 receptor agonists including liraglutide (Victoza/Saxenda). The molecule was engineered with a C-18 fatty diacid chain attached via a linker to enable albumin binding and extend the half-life to approximately one week, allowing once-weekly dosing. It received FDA approval for type 2 diabetes as Ozempic in December 2017, followed by approval for chronic weight management as Wegovy in June 2021 at a higher dose. The oral formulation Rybelsus was approved in 2019, becoming the first oral GLP-1 available. The SELECT cardiovascular outcomes trial (2023) demonstrated a 20% reduction in major adverse cardiovascular events, expanding its clinical significance.
Semaglutide's tolerability profile is well-characterized from extensive clinical trials involving thousands of patients. Gastrointestinal side effects (nausea, vomiting, diarrhea, constipation) are most common and typically occur during dose titration, improving over weeks as the body adjusts. Approximately 5-10% of trial participants discontinued due to GI side effects. Slow dose titration over 16-20 weeks significantly improves tolerability. Serious but rare risks include pancreatitis and, in animal studies, medullary thyroid carcinoma (leading to a boxed warning). Overall, the benefit-risk profile was deemed favorable enough for FDA approval across multiple indications.
Dose Range
250-1000 mcg
Frequency
Once weekly (SubQ)
Duration
Ongoing as prescribed
Dose Range
2400 mcg
Frequency
Once weekly (SubQ, after 16-week titration)
Duration
Ongoing as prescribed
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
3 mg
Water Type
Pre-filled pen (pharmaceutical) — no reconstitution needed
Mixing Volume
N/A (pre-filled) mL
Half-Life
~7 days (168 hours)
Molecular Weight
4113.6 Da
Ozempic/Wegovy are supplied as pre-filled injection pens. Store refrigerated at 2-8°C before first use. After first use, can be stored at room temperature (up to 30°C) for 56 days. Compounded semaglutide is reconstituted with bacteriostatic water.
FDA Status
FDA approved. Ozempic (2017) for type 2 diabetes, Rybelsus (2019) oral for diabetes, Wegovy (2021) for chronic weight management.
Legal Status
Prescription medication. Available through pharmacies with valid prescription. Compounded versions available through 503B pharmacies.
USA
ApprovedOzempic (2017), Wegovy (2021), Rybelsus (2019)
EU
ApprovedEMA authorized for diabetes and weight management
UK
ApprovedMHRA licensed Ozempic and Wegovy
Australia
ApprovedTGA approved Ozempic for diabetes, Wegovy pending
Canada
ApprovedHealth Canada approved for diabetes and obesity
Japan
ApprovedApproved for type 2 diabetes
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF
New England Journal of Medicine (2021)
STEP 1 trial demonstrating that 2.4 mg weekly semaglutide produced a mean body weight reduction of 14.9% versus 2.4% with placebo over 68 weeks in adults with obesity.
View Study →Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T
New England Journal of Medicine (2016)
SUSTAIN-6 trial showing that semaglutide significantly reduced the risk of major adverse cardiovascular events compared to placebo in patients with type 2 diabetes.
View Study →Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esber S, Inzucchi SE, Kosiborod MN, Lingvay I, Mosenzon O, Pieber TR, Sattar N, Wanner C, Husain M
New England Journal of Medicine (2023)
SELECT trial demonstrating a 20% reduction in major adverse cardiovascular events with semaglutide in overweight or obese adults without diabetes.
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