Every blockbuster drug has a molecule at its center and, somewhere behind it, scientists who refused to abandon a difficult problem.
For the GLP-1 medicines that have transformed diabetes and obesity treatment, one of those scientists is Lotte Bjerre Knudsen.
Working at Novo Nordisk, the Danish researcher helped lead the development of long-acting GLP-1 medicines, including liraglutide and semaglutide, the molecules behind products such as Victoza, Saxenda, Ozempic and Wegovy.
Her story is not one of a sudden discovery. It is a story about engineering patience: taking a naturally occurring gut hormone that the body eliminates within minutes and helping turn it into a medicine with effects that can last for days.
The distinction matters because the modern GLP-1 industry was built through different scientific contributions. Discovering a hormone, identifying its active form, understanding its physiology and engineering it into a usable drug are related achievements, but they are not the same achievement.
Knudsen’s contribution lay primarily in the last of those challenges, although her work extended far beyond a single molecule.
Who Is Lotte Bjerre Knudsen?
Lotte Bjerre Knudsen is a Danish biotechnology scientist who spent more than three decades working at Novo Nordisk.
She studied biotechnology and chemical engineering at the Technical University of Denmark and later earned a higher doctoral degree in medicine from the University of Copenhagen.
Her association with Novo began before she had completed her university education.
In an April 2026 account of her career, Knudsen described starting an internship in 1987, completing her university thesis at the company in 1988 and joining full-time in 1989.
Her earliest work was not on obesity medicines.
In a published interview with physician-scientist Eric Topol, she explained that she initially worked in the company’s industrial enzyme business, where she was involved in chemistry and enzyme-related research.
Her transition into pharmaceutical research occurred when a senior colleague began assembling a team to explore new approaches to treating type 2 diabetes.
GLP-1 became one of the group’s research interests.
By 1991, Knudsen and colleagues had begun working on GLP-1-based medicines. She later took on leadership responsibilities in the project and became central to the development of liraglutide.
The path was long. The research started years before any GLP-1 medicine developed by her team reached the market.
Knudsen would eventually hold senior scientific positions within Novo Nordisk, including Scientific Vice President and Chief Scientific Advisor in Research and Early Development.
Her work helped establish a commercial application of peptide biology that would become one of the most consequential developments in modern metabolic medicine.
The Problem With a Promising Hormone That Disappeared Too Quickly
GLP-1, or glucagon-like peptide-1, is a hormone released by intestinal cells after eating.
It helps regulate glucose-dependent insulin secretion, influences gastrointestinal activity and participates in pathways involved in appetite and energy balance.
Those properties made it an attractive candidate for treating type 2 diabetes.
The scientific foundation had been established by researchers including Joel Habener, Svetlana Mojsov and their collaborators, whose work helped identify the hormone’s physiologically active form and demonstrate its biological effects.
But there was an obvious problem.
Natural active GLP-1 has a circulating half-life of only a few minutes.
The enzyme dipeptidyl peptidase-4, or DPP-4, rapidly degrades the peptide, while additional processes contribute to its clearance from circulation.
That rapid disappearance is compatible with the hormone’s normal biological role, but it makes sustained therapeutic exposure difficult without modifying the molecule or its delivery.
Simply injecting natural GLP-1 would not provide the kind of long-lasting effect needed for convenient chronic treatment.
Drug researchers therefore had to address two challenges: preserve the hormone’s useful receptor activity and extend the time it remained available in the body.
Several approaches were considered, including formulations designed for slower release and modifications intended to resist enzymatic degradation.
Knudsen’s team ultimately pursued a strategy based on attaching a fatty-acid chain to the peptide.
This modification allowed the molecule to associate with albumin, an abundant protein in blood plasma that transports numerous substances.
Albumin binding can reduce the rate at which a peptide is filtered by the kidneys and help protect it against degradation.
The modified peptide can associate reversibly with albumin while remaining capable of activating its intended receptor.
The central insight was that a hormone did not necessarily need a completely new biological target to become a useful drug. Its chemical properties could be changed to make its activity last longer.
The hormone already had useful biology. The engineering challenge was keeping it in circulation long enough to become a practical treatment.
Liraglutide: The First Major Breakthrough in Her Drug-Development Work
The first major success of Knudsen’s research program was liraglutide.
In a scientific account published in 2019, Knudsen described joining the GLP-1 project in 1991, becoming its drug-discovery project manager in 1995 and playing a leading role in the invention of liraglutide in 1997.
Her account is especially valuable because it documents the scientific development from the perspective of someone directly involved. It is also a first-person account by an inventor with an acknowledged commercial connection to the medicine.
Liraglutide is a modified GLP-1 analogue with a fatty-acid side chain that promotes reversible albumin binding.
The chemical design extends its duration of action sufficiently for once-daily administration.
That was a major improvement over natural GLP-1, which is rapidly degraded after entering circulation.
But molecular engineering was only the beginning.
Researchers still had to investigate pharmacology, toxicology, manufacturing, clinical efficacy and safety before regulatory authorities could evaluate the medicine.
Liraglutide was authorized in Europe as Victoza for type 2 diabetes in 2009 and approved by the U.S. Food and Drug Administration in 2010.
Further clinical investigation supported its use for chronic weight management, leading to FDA approval of the higher-dose formulation marketed as Saxenda in 2014.
The transition from a diabetes medicine to an obesity treatment reflected an important evolution in GLP-1 research.
Researchers increasingly recognized that the hormone influenced appetite and body weight in addition to glucose regulation.
Knudsen and her collaborators had helped make that biological possibility accessible through an actual medicine.
The commercial success that followed should not obscure the years of experiments, manufacturing development and clinical research required to establish the product.
Liraglutide demonstrated that chemical modification of a naturally occurring peptide could create a practical treatment for chronic metabolic disease.
Its limitation was that patients still needed daily injections.
The next challenge was to make a related molecule last substantially longer.
From Liraglutide to Semaglutide: Making a Hormone Last a Week
Semaglutide represented another step in the engineering of GLP-1-based medicines.
Instead of designing a molecule suitable for daily dosing, Novo Nordisk researchers sought an analogue capable of maintaining therapeutic exposure for approximately one week.
The scientific work was collaborative.
A 2015 paper in the Journal of Medicinal Chemistry, led by Jesper Lau and coauthored by scientists including Lotte Bjerre Knudsen and Thomas Kruse, described the discovery and optimization of semaglutide.
The molecule contains specific changes to the GLP-1 peptide structure.
One amino-acid substitution makes semaglutide resistant to cleavage by DPP-4, while another helps direct the attachment of a fatty-acid modification to a selected position.
A C18 fatty di-acid side chain and linker promote strong but reversible binding to albumin.
These modifications help protect the peptide from rapid degradation and slow its clearance.
In humans, semaglutide has an elimination half-life of approximately one week.
The development changed the practical administration of GLP-1 therapy. Semaglutide injections could be given once weekly rather than once daily.
Semaglutide received FDA approval as Ozempic for type 2 diabetes in December 2017.
In June 2021, the FDA approved semaglutide as Wegovy for chronic weight management in an eligible patient population.
Additional semaglutide formulations, including oral products, would later expand the available administration options.
The distinction between molecular half-life and dosing schedule remains important. An oral formulation faces different absorption challenges from an injection, even when the active molecule is the same.
Semaglutide’s scientific significance therefore goes beyond any one brand.
It demonstrated how peptide sequence modification, fatty-acid attachment and albumin binding could be combined to substantially extend drug action.
The technique helped establish a foundation for later generations of peptide therapeutics.
Companies continue exploring longer-acting formulations, including approaches such as Novo Nordisk’s work with long-acting injection technology.
The underlying question remains familiar: how can a therapeutic molecule maintain useful activity while reducing the burden of administration?
The Lasker Award, the Breakthrough Prize and the Question of Scientific Credit
Scientific recognition arrived after decades of research and commercial development.
On September 19, 2024, the Lasker Foundation announced that Lotte Bjerre Knudsen would share the Lasker-DeBakey Clinical Medical Research Award with Joel Habener and Svetlana Mojsov.
The prize recognized their complementary contributions to discovering and developing GLP-1-based medicines for obesity.
Habener’s work helped establish the molecular biology of the hormone, while Mojsov’s research was central to identifying and characterizing its physiologically active form.
Knudsen’s contribution centered on translating GLP-1 biology into practical pharmaceutical development.
These were different stages of scientific progress, carried out by researchers and teams working across institutions and decades.
In April 2025, Knudsen received another major honor when she shared the Breakthrough Prize in Life Sciences with Daniel J. Drucker, Habener, Jens Juul Holst and Mojsov.
The recognition reinforced the collaborative nature of the GLP-1 story.
The modern drug industry often presents new medicines through the companies that manufacture and sell them.
Clinical trial results, regulatory announcements and commercial sales tend to place brand names at the center of public attention.
The people who spent years establishing the underlying science can be less visible.
Knudsen’s career illustrates an especially important form of scientific work: applied drug discovery inside a pharmaceutical company.
That work depends on scientists trained in different disciplines, including medicinal chemistry, pharmacology, molecular biology, toxicology and pharmaceutical development.
It also depends on earlier discoveries made in academic laboratories.
The study of GLP-1 receptors belongs to a larger history of receptor biology, including work such as Robert Lefkowitz’s contributions to understanding G protein-coupled receptors.
Knudsen’s recognition does not diminish the achievements of other contributors. It helps identify a part of the process that is sometimes overlooked: turning an interesting biological mechanism into a medicine that can be manufactured, evaluated and prescribed.
After 36 Years at Novo Nordisk, What Does Her Career Leave Behind?
Knudsen’s professional story entered a new chapter in 2026.
In April, she announced her departure from Novo Nordisk after approximately 36 years of full-time employment.
In a public account of her departure, she reflected on beginning as a student in the late 1980s and spending much of her professional life working alongside scientists who helped establish long-acting GLP-1 medicines.
Her departure does not change the scientific record.
By then, liraglutide and semaglutide had become established examples of how the pharmacological properties of a peptide could be modified to make it suitable for chronic treatment.
Yet their success does not settle every question about the medicines.
Gastrointestinal adverse effects, the management of long-term therapy, weight regain after discontinuation, affordability and access remain important subjects of clinical and public-health discussion.
Making a drug molecule last longer does not automatically determine which patients should receive it, how treatment should be funded or how its long-term risks and benefits should be managed.
Those questions require continuing research and medical evaluation.
The industrial implications are also continuing to evolve.
Drug developers now investigate new receptor combinations, more convenient delivery systems and approaches intended to extend the duration of biological activity.
Some programs aim for longer injection intervals. Others seek oral delivery or new ways to influence metabolic signaling.
The commercial landscape has changed dramatically, but one of the core design questions remains the one that shaped Knudsen’s early career.
How can scientists take a molecule that already performs a useful biological function and make it behave like a reliable medicine?
For Knudsen and her colleagues, the answer involved molecular modification, albumin binding and years of experimental work.
The story is more complex than the idea that one scientist invented Ozempic in a single breakthrough.
It begins with the discovery of GLP-1 and its active forms, continues through basic biological research, and reaches pharmaceutical development through multidisciplinary teams.
Knudsen helped lead one of the decisive stages of that journey.
Her enduring contribution was helping turn a hormone that survived only minutes into a family of medicines capable of changing clinical practice.
That transformation did not happen overnight. It required the kind of persistence that rarely appears in a pharmaceutical advertisement but often determines whether a scientific idea becomes a medicine.
In the history of GLP-1 therapeutics, the molecule matters. So do the scientists who learned how to make it last.
Sources and Further Reading
- Lasker Foundation: GLP-1-Based Therapy for Obesity — 2024 Lasker-DeBakey Clinical Medical Research Award.
- Knudsen LB. Inventing Liraglutide, a Glucagon-Like Peptide-1 Analogue, for the Treatment of Diabetes and Obesity. ACS Pharmacology & Translational Science, 2019.
- Lau J, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 Analogue Semaglutide. Journal of Medicinal Chemistry, 2015.
- Proceedings of the National Academy of Sciences: Q&As with Svetlana Mojsov, Joel Habener and Lotte Bjerre Knudsen, winners of the 2024 Lasker-DeBakey Clinical Medical Research Award.
- Aarhus University: Pharmaceutical Researcher Is New Honorary Professor at Health, December 18, 2015.
- Breakthrough Prize Foundation: 2025 Breakthrough Prize Laureates in Life Sciences, April 5, 2025.
- Nordic Life Science: Lotte Bjerre Knudsen Leaves Novo Nordisk, April 13, 2026.
- U.S. Food and Drug Administration: GLP-1 Receptor Agonist Approval History and Safety Information.
