The History of Semaglutide

Semaglutide did not appear overnight. It rests on nearly forty years of hormone research, and on an earlier Novo Nordisk medicine that showed which chemical tricks could keep a fragile peptide in the body for longer.

The Discovery of GLP-1

In the early 1980s, scientists studying the gene for glucagon found that it also coded for other, unknown peptides. Work by teams in Boston and Copenhagen, including Joel Habener, Svetlana Mojsov and Jens Juul Holst, showed that one of them, GLP-1, strongly boosts insulin release. In 2024 Habener, Mojsov and Novo Nordisk scientist Lotte Bjerre Knudsen received the Lasker Award for the discoveries that led to GLP-1 medicines.

The Problem of a Two-Minute Hormone

Natural GLP-1 looked like an ideal diabetes treatment, except that the body clears it almost as soon as it appears. The first drug to get round this was exenatide, a peptide originally found in the saliva of the Gila monster lizard. It was approved in the US in 2005 and was injected twice a day.

Liraglutide Shows the Way

Novo Nordisk took a different route. By attaching a fatty acid to human GLP-1, it made liraglutide, which binds albumin and lasts long enough for one injection a day. It was approved for diabetes as Victoza in 2009 in Europe and 2010 in the US, and later for weight management as Saxenda. Liraglutide proved the fatty acid approach worked, and its developers then aimed for a once-weekly version.

Designing a Weekly Molecule

The team tested many combinations of fatty acid, linker and amino acid changes. The winning candidate, published in 2015 by Jesper Lau and colleagues, combined an 18-carbon diacid chain with protection against DPP-4. In mini-pigs it had a half-life of about 46 hours, which pointed to weekly dosing in humans. It was given the name semaglutide.

Clinical Programmes

Novo Nordisk gave each of its main study series a name. SUSTAIN tested weekly injections in type 2 diabetes, and PIONEER tested the tablet. STEP covered weight management, and SELECT, FLOW and ESSENCE later studied heart, kidney and liver outcomes. The studies page summarises the main results.

Approval Milestones

• December 2017: the FDA approved Ozempic, a weekly injection for adults with type 2 diabetes. The European Commission followed in February 2018.
• September 2019: Rybelsus became the first GLP-1 medicine in tablet form approved in the US. EU authorisation followed in April 2020.
• June 2021: the FDA approved Wegovy, semaglutide 2.4 mg, for chronic weight management. The EU authorised it in January 2022.
• December 2022: the US approval of Wegovy was extended to adolescents aged 12 and over.
• March 2024: based on SELECT, the FDA added a reduction in the risk of heart attack, stroke and cardiovascular death to Wegovy's label for people with heart disease and excess weight.
• January 2025: the FDA approved Ozempic to lower the risk of kidney failure, worsening kidney disease and cardiovascular death in people with type 2 diabetes and chronic kidney disease.
• August 2025: Wegovy received accelerated approval in the US for adults with MASH, a serious form of fatty liver disease, with moderate to advanced liver scarring.

Demand and Shortages

Demand grew faster than production. Health authorities in Europe and the US reported shortages of semaglutide medicines from 2022, and European regulators asked doctors to prioritise patients with diabetes for Ozempic. The FDA declared the US shortage over in February 2025, after Novo Nordisk had expanded its manufacturing.

What Comes Next

Research continues into higher doses, new tablet forms, combinations with other hormones and conditions ranging from osteoarthritis to addiction. Approved uses still differ between the EU, the UK and the US, and each new use needs its own evidence and regulatory review.