Scientists Who Pioneered GLP-1 Drugs Bag Breakthrough Prize

he Breakthrough Prize Foundation announced the winners of this year’s Breakthrough Prizes today (April 5). Popularly called the “Oscars of Science,” these awards honor groundbreaking discoveries that transform our understanding of living systems and advance efforts to extend human life.

Image of Breakthrough Prize laureate, endocrinologist Daniel Drucker, against a yellow background. He wears a navy-blue jacket and smiles. — Endocrinologist Daniel Drucker won the Breakthrough Prize in Life Sciences for his work in characterizing GLP-1.
Dianne Matthews

One of this year’s Life Sciences prizes was jointly awarded to five scientists for the discovery and characterization of glucagon-like peptide 1 (GLP-1), revealing its potential in treating diabetes and obesity. The awardees are Daniel Drucker, an endocrinologist at the University of Toronto, Joel Habener, an endocrinologist at Harvard Medical School, Jens Juul Holst, a physiologist at the University of Copenhagen, Lotte Bjerre Knudsen, a pharmaceutical scientist at Novo Nordisk, and Svetlana Mojsov, a chemist at The Rockefeller University.

“[It’s been] an interesting journey,” said Knudsen, who admitted that she never expected to receive academic prizes as an industry scientist. Although grateful for the recognition, she noted that this has been a huge team effort. “When you see a success story like GLP-1, there are multiple inventors.”

Investigating Incretins

The pancreas secretes insulin in response to high blood sugar, helping liver, fat, and skeletal muscle cells absorb glucose, reducing its levels in the blood. In the 1960s, researchers found that orally administered glucose triggers greater insulin production than glucose delivered directly into the bloodstream, indicating that some gut hormones—incretins—respond to food, leading to insulin production.¹

In the 1980s, Habener was working at Massachusetts General Hospital (MGH) and studying hormones, including glucagon, which increases blood glucose, in type 2 diabetes. On cloning the gene encoding glucagon, they discovered that it also encoded a related hormone, which scientists would later call GLP-1.²

Photo of Breakthrough Prize laureate, endocrinologist Joel Habener against a blue background. He wears a blue shirt, blue tie, and black blazer. — Endocrinologist Joel Habener received this year’s Breakthrough Prize in Life Sciences for his work on discovering and characterizing GLP-1.
MGH Photo Laboratory

Around the same time, scientists determined the sequences of the human glucagon and GLP-1 proteins.³ Mojsov, then a newly independent researcher at MGH, was familiar with glucagon from her graduate research days, so she knew which region of the protein showed hormonal activity. She immediately recognized a similar region in GLP-1.

“By the time I finished my studies with glucagon, I really knew its sequence by heart, backwards and forwards,” said Mojsov. “It was that knowledge of glucagon sequence, and its biology…which actually was very critical for my discovery of GLP-1.”

Mojsov went on to make antibodies against the active form of GLP-1, which she, along with Habener, used to detect the peptide in rat intestines.⁴ Simultaneously, Drucker, a postdoctoral fellow in Habener’s lab, used GLP-1 synthesized by Mojsov to show that its active form could stimulate insulin release from rat pancreas.⁵ Around the same time, halfway across the world at the University of Copenhagen, Holst and his colleagues isolated GLP-1 from pigs and found that it increased pancreatic insulin secretion.⁶

Photo of Breakthrough Prize laureate, physician Jens Juul Holst against a white background. He wears a blue shirt and smiles. — Physiologist Jens Juul Holst received the 2025 Breakthrough Prize in Life Sciences for his work on discovering and characterizing GLP-1.
Lars Svankjær, The Royal Danish Academy of Sciences and Letters

Over the next few years, the teams at MGH and University of Copenhagen independently tested the effects of supplemental GLP-1 in people and found that infusing its biologically active form stimulated insulin secretion and lowered blood glucose.^7,8 Mojsov realized the implication of their discovery while analyzing the data with a lab technician. “I remember both of us looking at the data, and we looked at each other and said, ‘Well, this is going to be a drug.’”

From Bench to Bedside

By the 1990s, scientists found that injecting GLP-1 into rats reduced their appetites.⁹ This suggested that, in addition to lowering blood sugar, the hormone might also help treat obesity, which piqued industry researchers’ interest in the molecule’s therapeutic potential.

Image of Breakthrough Prize laureate, pharmaceutical scientist Lotte Bjerre Knudsen against a grey background. She wears a pink shirt and blazer and smiles. — Pharmaceutical scientist Lotte Bjerre Knudsen won this year’s Breakthrough Prize in Life Sciences for her work on developing effective anti-diabetic and anti-obesity treatments based on GLP-1.
Petra Kleis

However, using GLP-1 as a drug posed a major challenge: The hormone underwent rapid metabolism, remaining in the blood for only a few minutes. Knudsen, newly returned to Novo Nordisk from maternity leave, was tasked with overcoming this obstacle. She wasn’t deterred. “I just thought, ‘Okay, I’m going to convince them,’” she said. “And it kind of became fun that way.”

Over time, researchers from various companies made several modifications to improve GLP-1’s stability, but faced setbacks, such as injection-site rash and even anaphylactic shock in some clinical trial participants.¹⁰

Learning from these obstacles, Knudsen investigated whether adding fatty acids to the peptide would increase its stability, creating a long-acting drug molecule. This led to the development of liraglutide, a GLP-1 analog that could be administered once daily.¹¹ Further chemical modifications of this molecule resulted in an even more stable drug, semaglutide, for a once-weekly dosage.¹²

Photo of Breakthrough Prize laureate, chemist Svetlana Mojsov against a brown background. She wears a violet top and white jacket and smiles. — Chemist Svetlana Mojsov won this year’s Breakthrough Prize in Life Sciences for her work on discovering and characterizing GLP-1.
Lori Chertoff, courtesy of the Rockefeller University

Since its approval by the US Food and Drug Administration in 2021, semaglutide has been sold under the brand names Ozempic, Rybelsus, and Wegovy as an anti-diabetic and anti-obesity treatment. GLP-1 drugs have generated billions of dollars in revenue and revolutionized the treatment of diabetes and obesity.

Meanwhile, scientists have been uncovering new roles of GLP-1-based drugs beyond diabetes and obesity, with early data suggesting that they may be used to treat cardiovascular diseases, addictive disorders, and neurodegenerative disorders.^13-15

Mojsov believes that this creates an ideal opportunity for industry-academia collaborations, allowing pharmaceutical researchers to observe drug effects in clinical trials while basic scientists investigate the underlying mechanisms. “We can lead each other,” Mojsov said. “There are a lot of very interesting questions ahead of us.”