Semaglutide is a modern compound, but the science it’s built on goes back more than forty years. It started with a gut hormone, a lizard, and a stubborn engineering problem: how to keep a fragile peptide alive in the body long enough to matter. Here’s the documented story of where semaglutide came from and how it was studied.
The GLP-1 groundwork (1980s–1990s)
In the 1980s, researchers working on the proglucagon gene identified a fragment produced by intestinal L-cells and named it glucagon-like peptide-1, or GLP-1. Scientists including Joel Habener, Svetlana Mojsov and Jens Juul Holst helped characterise the peptide and its role in the “incretin effect” — the observation that gut hormones prompt insulin release after a meal. GLP-1 looked promising as a diabetes target. It had one fatal flaw: the enzyme DPP-4 chewed it up within minutes.
The bigger break came in 1992, when John Eng, working at a Veterans Affairs medical centre in New York, isolated a peptide from the venom of the Gila monster. Called exendin-4, it behaved like GLP-1 but resisted rapid breakdown. That discovery became exenatide, which the FDA approved in 2005 as Byetta — the first GLP-1 receptor agonist on the market. It proved the class could work. It also showed how much room there was to improve on it.
Liraglutide and the acylation platform (2000–2014)
At Novo Nordisk in Denmark, a team led by Lotte Bjerre Knudsen took a different route to durability. Rather than borrow a lizard peptide, they modified human GLP-1 itself and attached a fatty-acid chain — a technique called acylation. The fatty acid lets the molecule bind reversibly to albumin in the blood, which shields it from enzymes and slows clearance.
That platform produced liraglutide, which entered clinical testing in 2000 and was approved as Victoza for type 2 diabetes in 2010. Liraglutide was a once-daily injection. The next question Novo Nordisk’s chemists set for themselves was harder: could the same approach stretch the compound’s life out to once weekly?
Engineering semaglutide (2008–2012)
The answer became semaglutide. A Novo Nordisk chemistry team including Jesper Lau and Thomas Kruse tested large numbers of linkers, fatty acids and amino-acid changes to build a more stable molecule. The published structure is precise: the peptide backbone carries substitutions that block DPP-4 degradation, and a longer di-acid fatty chain is coupled to the lysine at position 26 through a hydrophilic linker. The result binds albumin more tightly than liraglutide and survives far longer in circulation. Semaglutide was described in the scientific literature around 2012, and it moved into a large clinical programme soon after.
Like the rest of its class, semaglutide is a GLP-1 receptor agonist — it binds the same receptor the natural hormone targets. Researchers have studied that receptor activity across metabolic and cardiovascular endpoints in the trials below.
The trial programmes (2016–2023)
Semaglutide was tested through several named study programmes, each with published results:
- SUSTAIN — the phase 3a programme for once-weekly injectable semaglutide, run across six trials in roughly 7,200 participants. SUSTAIN-6, published in the New England Journal of Medicine in 2016, was designed as a cardiovascular safety study in people with type 2 diabetes. On the strength of this programme, injectable semaglutide (Ozempic) was approved by the FDA in December 2017.
- PIONEER — a programme testing an oral tablet formulation, difficult because peptides are normally destroyed in the stomach. The oral version (Rybelsus) was approved by the FDA in September 2019 as the first GLP-1 analogue available as a pill.
- STEP — a programme studying a higher-dose formulation in people with overweight or obesity. STEP 1, published in the New England Journal of Medicine in 2021, reported a mean body-weight change of about −14.9% over 68 weeks versus −2.4% for placebo.
- SELECT — published in the New England Journal of Medicine in 2023, this trial reported a roughly 20% reduction in major adverse cardiovascular events among participants with overweight or obesity but without diabetes.
Where the research stands now
Semaglutide is now one of the most heavily studied compounds in metabolic science, and the published record keeps growing. Investigators have reported findings in areas ranging from cardiovascular and kidney endpoints to metabolic liver disease, and newer work continues to probe the GLP-1 pathway and next-generation dual and triple receptor agonists built on the same acylation idea Knudsen’s group pioneered. The lineage is unusually well documented: from a gut hormone in the 1980s, through lizard venom and liraglutide, to a once-weekly molecule engineered atom by atom.
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Research use only
Semaglutide is supplied by Vero Labs strictly as a research compound for laboratory and scientific investigation. It is not intended for human or animal consumption, and nothing above should be read as medical advice or a description of outcomes any individual should expect. Every batch is independently third-party lab-tested, with a published Certificate of Analysis (COA) available for verification.