How liraglutide and semaglutide were discovered and developed into licensed medicines

Picture the moment that started everything: a lab measuring what happens after a meal

In the early 1980s, researchers studying gut physiology noticed something odd. A fragment of a proglucagon gene (the same gene family that produces glucagon) was expressed in intestinal cells, not just the pancreas. The peptide it encoded, later named glucagon-like peptide-1, or GLP-1, turned out to do something remarkable: it told the pancreas to release insulin in proportion to how much glucose was present, and it signalled the brain to reduce appetite and slow gastric emptying. The name for this coordinated response, "incretin effect", was already established; GLP-1 was the missing piece that explained a large part of it.

The problem was obvious to any pharmacologist looking at it. Native GLP-1 lasts in the bloodstream for around two minutes before an enzyme called DPP-4 breaks it down. Useful as a hormone; useless as a drug in its natural form. The challenge set for Novo Nordisk's chemists was to build something that behaved like GLP-1 but survived long enough to do clinical work. You can get a sense of how that challenge was framed (and ultimately answered) by reading the account of semaglutide's discovery in more detail, but the short version is: fatty-acid attachment.

By anchoring a long fatty-acid chain to the GLP-1 backbone, the molecule could bind reversibly to albumin (the most abundant protein in blood plasma) which shielded it from DPP-4 and dramatically slowed its clearance. Liraglutide used a C16 fatty acid attached via a linker; semaglutide later used a longer C18 chain with a different linker architecture, pushing its half-life from around 13 hours (liraglutide) to roughly seven days. That single pharmacokinetic shift is why liraglutide requires a daily injection while semaglutide needs only one weekly dose, and if you are curious about whether liraglutide and semaglutide are actually the same thing, the structural differences between the two molecules help explain why they are not.

Liraglutide reached patients first, and taught the field what GLP-1 medicines could do

Liraglutide entered clinical development at Novo Nordisk in the mid-1990s, originally as a treatment for type 2 diabetes. It received regulatory approval for diabetes in Europe in 2009, branded as Victoza. The weight-loss signal noticed during those diabetes trials was substantial enough to prompt a dedicated obesity programme: the SCALE trials, which established liraglutide 3mg daily as the dose for weight management. It was subsequently licensed for obesity under the name Saxenda.

Those trials mattered beyond their own results. They provided the first large-scale human evidence that a GLP-1 medicine could produce clinically significant, sustained weight reduction in people without diabetes, not as a side-effect, but as the primary aim. That proof of concept cleared the conceptual path for the semaglutide programme that followed. If you want to explore how liraglutide and semaglutide compare as medicines now that both are licensed, the differences in dosing frequency and average weight-loss outcomes are worth understanding before any clinical conversation.

It is worth noting that Saxenda (liraglutide) is not dispensed by nume. Our prescribers work with the medicines currently licensed and available through our pharmacy, if you are weighing your options, the weight-loss treatment page sets out what is currently offered. That said, understanding liraglutide's history is genuinely useful: it explains why the field moved toward once-weekly dosing, and why semaglutide's development was, in a real sense, liraglutide's sequel.

Semaglutide: engineered for once-weekly dosing, then pushed further still

Semaglutide's development began with a specific engineering brief: could the fatty-acid approach be refined to achieve a half-life long enough for once-weekly injection? The scientists who discovered semaglutide modified the GLP-1 backbone at two positions (replacing one amino acid to resist DPP-4 cleavage, and substituting another to prevent albumin binding at the wrong site) then attached the longer fatty-acid chain via a hydrophilic linker. The result was a molecule with a half-life of approximately 165–184 hours: close enough to seven days to make once-weekly injection practical.

The STEP clinical trial programme, which included STEP 1 published in the New England Journal of Medicine, demonstrated that semaglutide 2.4mg once weekly produced an average weight reduction of around 15% over 68 weeks in adults with obesity. That was a step-change from what liraglutide had achieved at its licensed obesity dose. The programme also led to a cardiovascular indication, establishing that semaglutide could reduce the risk of major cardiovascular events in eligible adults, a benefit that went well beyond weight.

Development did not stop at the injection. Novo Nordisk's scientists then tackled a harder problem: oral bioavailability. GLP-1 analogues are peptides; stomach acid and gut enzymes destroy them efficiently. The solution was co-formulation with SNAC (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), an absorption enhancer that temporarily alters the local pH around the tablet in the stomach and facilitates absorption of semaglutide through the gastric epithelium. The result is the Wegovy tablet, which the MHRA approved in June 2026 as the first oral GLP-1 medicine licensed in the UK for weight management. A one-minute habit worth forming: before ordering any GLP-1 medicine online, check the dispensing pharmacy appears on the GPhC pharmacy register, it takes seconds and confirms you are dealing with a regulated UK operation.

The broader story of semaglutide's development spans two decades and three distinct product forms, injectable Ozempic for type 2 diabetes, injectable Wegovy for weight management, and now the Wegovy tablet. Each form came from the same molecular starting point; each required its own regulatory approval. The MHRA licenses UK medicines on the basis of UK or referenced EU data, and the NHS medicines page for semaglutide reflects the current licensed uses and important safety information.

What is licensed for weight loss in the UK today, and where semaglutide sits

Two injectable GLP-1 medicines are currently licensed in the UK for weight management: semaglutide (Wegovy injection) and tirzepatide (Mounjaro). Liraglutide (Saxenda) holds a licence but is not dispensed by nume. The Wegovy tablet, approved in June 2026, is the first oral option in this class approved by the MHRA for weight management, earlier in the approval timeline than anywhere else in Europe.

Tirzepatide is a dual GIP and GLP-1 receptor agonist made by Eli Lilly; it activates two receptor pathways rather than one, which is why its mechanism is sometimes described as distinct from the semaglutide lineage even though it shares the weight-loss aim. NICE appraised both medicines (tirzepatide under TA1026 and semaglutide under TA875) and the eligibility criteria differ in ways a prescriber will walk through with you.

If you are trying to work out which of the currently available medicines might suit your situation, the right starting point is a clinical conversation rather than a history of drug development. Our prescribers review every consultation personally, no automated decision, a named clinician reading your answers. The weight-loss overview gives a grounded comparison of the options, and when you are ready, starting a free consultation through our treatment page connects you with that clinical review.