Exclusive interview: Jens Juul Holst

Jens Juul Holst, a professor of medical physiology at the University of Copenhagen, is the man who made “gut” hormones famous world-wide. In 1986, he and his research team discovered glucagon-like peptide 1, known to most as GLP-1. GLP-1 is an intestinal hormone that controls the glucose-induced gastrointestinal stimulation of insulin secretion, regulating the metabolism. Juul Holst and others spent decades researching and tweaking it so it could be used in medications.

The greatest obstacle to utilizing the hormone was the extremely short half-life of GLP-1, which required special modifications to the molecule to extend the duration of action.”

“The greatest obstacle to utilizing the hormone was the extremely short half-life of GLP-1, which required special modifications to the molecule to extend the duration of action,” explains Holst to Nordic Life Science.

That research spawned GLP-1 agonists, a class of medications that help manage blood glucose levels in people with type 2 diabetes, as well as a game-changing family of drugs, including Novo Nordisk’s Ozempic and Wegovy, to treat obesity that are selling out almost as quickly as they arrive in pharmacies.

A new way to treat diabetes

The medications that evolved from GLP-1 have shown a marked success in tackling both obesity and diabetes. People who are obese and have type 2 diabetes often recover from their diabetes if they lose enough weight.

“It’s extremely promising to think of these medicines as a new and better treatment than ever for type 2 diabetes,” says Holst.

Using insulin can adjust glucose levels, but it is difficult to regulate glucose safely, Holst explains. “It’s easier to treat type 2 diabetes with GLP-1. We still don’t know all the long-term effects of GLP-1, but we know the long-term effects of bariatric surgery, which are probably similar; longer life expectancy and fewer complications,” he emphasizes.

Medication plus lifestyle changes

As for enabling weight loss, GLP-1 inhibits the appetite and reward centers in the brain.

“So, when you are on GLP-1, you lose your appetite and eat less,” says Holst. “Then you lose weight. Another way to view it is that if you have a health problem, GLP-1 helps you to solve it.”
The weight-loss drugs have been praised for their success but are not without their critics. Some users have complained of side effects such as nausea and other gastro-intestinal distress and regaining weight once they stopped using the drugs.

“When something happens, people get upset; there will always be some cases where people have reactions,” objects Holst.

It takes about a year and a half on the weight-loss drugs to reach the maximum effect. In some trials where the drug therapy was interrupted, part of the weight loss was maintained after some time, but otherwise it is important to make lifestyle improvements to maintain the weight loss, such as exercising and eating a healthier diet. With exercise it may be possible to maintain weight loss at least another year.

I don’t have the complete vision of what will happen long term for people using the weight loss drugs. One aspect of it is that only about 40 percent of people are on medications after a year, and we don’t know why.”

“That’s very important. You have to continue to do something to maintain your new weight besides using the medications. Making these lifestyle changes is a tremendous help,” says Holst.  “I don’t have the complete vision of what will happen long term for people using the weight loss drugs. One aspect of it is that only about 40 percent of people are on medications after a year, and we don’t know why,” continues Holst.

One thing that is certain however, is that the need for weight-loss aids continues to grow. “Obesity is becoming a bigger problem in the Nordics too, although it’s not yet as serious as it is in the U.S.,” says Holst. “People are worried about this development and what we can do about it. Public awareness about obesity is great, and looking at what we can do to reverse it, but if we’re not physically active, it’s hard to see how we can stay healthy for a long time.”

A lot of surplus money going to science

Based on Novo Nordisk’s huge financial success with Wegovy and Ozempic, some say the company is reshaping Denmark’s economy. Its share price has tripled in three years, and last year there were reports that the company was valued at more than the entire Danish economy. Novo Nordisk’s success in this new category of obesity and diabetes medications will likely have a huge effect on life sciences in Denmark as well, notes Holst.

“There will be a lot of surplus money going to science,” he predicts. “These companies are constantly striving to produce stronger more powerful agents. Funding will be applied to other areas of research with which Novo Nordisk is involved.”

Danish researchers have focused on metabolic diseases for a while and Holst says that he expects that to continue.

“We have a well-educated population, we have money and collaboration between institutions,” he explains. “Certainly, we do see collaboration between industry, academia and the government, and scientists doing research in other countries.”

Holst himself has also co-founded companies based on his research, including Antag Therapeutics, which is developing a novel therapeutic peptide for metabolic and cardiovascular autonomic diseases, and Bainan Biotec, which has a first-in-class-drug in pre-clinical development for the treatment of osteoporosis.

Bariatric surgery

Jens Juul Holst is a professor at the Department of Biomedical Sciences at the University of Copenhagen, and at the same time affiliated with the Novo Nordisk Foundation Center for Basic Metabolic Research. His current research focuses on exploring the impact of bariatric surgery on maintaining weight and on diabetes. During bariatric surgery, the stomach is surgically constricted, so food bypasses the stomach and travels to the lower part of the small intestine, the home of molecules that regulate the secretion of GLP-1. This causes secretions of GLP-1 that are up to 30 times higher than usual with positive effects on blood glucose levels, insulin secretion, appetite, food intake, and weight.

We are trying to digest and understand what has happened in the past few years with bariatric surgery.”

“We are trying to digest and understand what has happened in the past few years with bariatric surgery,” he says. “We are focusing on the secretion of GLP-1. After bariatric surgery, there is a huge release.”

Enjoy your work

Last year Holst won the Novo Nordisk Foundation Lecture prize, which came with an award of DKK 500,000 for research and DKK 100,000 for him personally.

Since he co-discovered GLP-1, he has contributed significantly to the combined scientific insights that have resulted in important new drugs for treating people with type-2 diabetes, which few have managed to do over the course of an entire career.”

“Jens is a true giant of research on incretin. He has made significant discoveries from pure basic research to clinical research. Since he co-discovered GLP-1, he has contributed significantly to the combined scientific insights that have resulted in important new drugs for treating people with type-2 diabetes, which few have managed to do over the course of an entire career. He is incredibly generous with his time for young researchers and new collaborations – and a really good lecturer,” explained Anna Krook, Chair of the Novo Nordisk Foundation’s Committee on Endocrinology and Metabolism, at the time of the announcement.

Although research methods have changed since Holst first set foot in a lab, he continues to enjoy his work and he advises young researchers to do the same.

I plan to keep going, we’re having fun.”

“I started doing research in 1972, I’m still a full-time professor and I’m still doing very exciting research and trying to find answers to health problems. I plan to keep going, we’re having fun,” he summarizes.

He also considers himself fortunate to continue to pursue research in areas in which he is passionate. “The work I’ve done has been extremely important. I’m a doctor and these health problems, obesity and diabetes complications, are what I’ve been interested in for years,” he concludes.