What it is
Semaglutide is a lab-made copy of a gut hormone called GLP-1. The body releases GLP-1 after a meal. It tells the pancreas to make insulin, tells the stomach to empty more slowly, and tells the brain the body is full. The natural hormone lasts only a couple of minutes. Semaglutide was engineered to last about a week, which is why the injection is given once a week.
Novo Nordisk sells it under several names. Ozempic is the diabetes injection, and since 2026 also the name of a daily diabetes tablet. Rybelsus is the original daily diabetes tablet. Wegovy is the weight-management version: a weekly injection, including a higher 7.2 mg dose sold as Wegovy HD, and, since December 2025, a daily tablet.
Semaglutide is a 31-residue GLP-1(7-37) analogue with three modifications to native GLP-1: an Aib substitution at position 8 conferring DPP-4 resistance, an Arg substitution at position 34 to prevent acylation at that lysine, and a C18 fatty diacid attached at Lys26 through a γGlu-2xOEG linker. The diacid drives high-affinity, reversible albumin binding, reducing renal clearance and yielding a plasma half-life of roughly one week. It is a full GLP-1 receptor agonist acting on pancreatic β-cells (glucose-dependent insulin secretion), α-cells (glucagon suppression), gastric motility and hypothalamic and hindbrain appetite circuits.
The oral formulations co-formulate semaglutide with SNAC (sodium N-(8-[2-hydroxybenzoyl]amino)caprylate), which locally raises gastric pH and promotes transcellular absorption across the gastric epithelium. Labeled absolute bioavailability is only about 0.4–1% for Rybelsus and 1–2% for Ozempic tablets, hence daily oral doses of 1.5–25 mg across the three tablet products, against 0.25–7.2 mg once weekly by injection.
Who made it and when
Novo Nordisk chemists led by Jesper Lau designed semaglutide in the mid-2000s as a longer-lasting follow-up to the company’s daily drug liraglutide. The compound patent was first filed in 2005, and the design work was published in 2015. Ozempic was approved in 2017, Rybelsus in 2019 and Wegovy in 2021. The company owns the core patents, which run into the early 2030s in the United States.
Semaglutide emerged from Novo Nordisk’s programme to extend the albumin-binding strategy used in liraglutide. Lau and colleagues described the structure–activity work in the Journal of Medicinal Chemistry in 2015. The compound patent, US 8,129,343 (priority March 2005, granted 2012), is held by Novo Nordisk; regulatory exclusivity and secondary formulation and dosing patents extend protection beyond the compound patent in most markets. US approvals: Ozempic 2017-12-05, Rybelsus 2019-09-20, Wegovy 2021-06-04, Wegovy tablets 2025-12-22 and the Wegovy 7.2 mg dose 2026-03-19. In January 2026 the FDA approved renaming a reformulated Rybelsus tablet (1.5, 4 and 9 mg) as Ozempic tablets.
What the data say
The big trials are consistent. In people with obesity and no diabetes, the 2.4 mg weekly dose cut body weight by about 15% over 16 months, against roughly 2% on placebo. A separate trial in people with existing heart disease found about one fifth fewer heart attacks, strokes and cardiovascular deaths. It also protected the kidneys in people with diabetes, and improved liver inflammation in MASH. A higher 7.2 mg dose produced about 19% weight loss, against about 16% at 2.4 mg. Two large Alzheimer’s trials of the tablet failed.
STEP 1 (n=1,961) reported a treatment difference of −12.4 percentage points in body weight at 68 weeks. SELECT (n=17,604) reported a hazard ratio of 0.80 for 3-point MACE over a mean 39.8 months. FLOW (n=3,533) reported a hazard ratio of 0.76 for the composite kidney outcome and was stopped early for efficacy. ESSENCE part 1 (first 800 of 1,197 participants) met both histological primary endpoints at 72 weeks. STEP UP (n=1,407) reported −18.7% with 7.2 mg vs −15.6% with 2.4 mg and −3.9% with placebo at 72 weeks (treatment-policy estimand), with dysaesthesia in 22.9% of the 7.2 mg group. EVOKE and EVOKE+ (n=3,808 combined) found no difference from placebo in CDR-SB change at 104 weeks despite improvements in Alzheimer’s biomarkers.
Regulatory picture
Semaglutide is fully FDA approved under its brand names. What is not approved is anyone else’s version. During the 2022–2025 shortage, compounding pharmacies were allowed to make copies. The FDA declared the shortage over in February 2025 and set deadlines in April and May 2025 for compounders to stop. Since then the FDA has sent warning letters to sellers of “compounded” or “research” semaglutide, and in February 2026 it announced steps to restrict the raw ingredient used in mass-marketed compounded copies.
Semaglutide is not on the 503A bulk drug substances list and does not need to be, because it is a component of FDA-approved drugs. Compounding of essentially-copies of an approved product is permitted only while the product appears on the FDA drug shortage list under section 503A(b)(1)(D) and 503B(a)(2)(A). With the shortage removed on 2025-02-21, that pathway closed on 2025-04-22 for 503A and 2025-05-22 for 503B; FDA confirmed in April 2026 that semaglutide is on neither the shortage list nor the 503B bulks list. FDA states it is aware of no lawful basis for compounding with semaglutide sodium or semaglutide acetate, which are different active ingredients from the approved drug. Personalised compounded formulations that differ materially from the approved product remain a contested area, and FDA’s February 2026 announcement signalled tighter control of GLP-1 active ingredients destined for non-approved compounded drugs.
