Discovering gut hormones: A conversation with Jens J. Holst, MD
For Jens J. Holst, MD, DMSc, there were long years spent “in the desert” studying how incretin hormones in the gut work before he and his team would go on to discover the peptide that would change type 2 diabetes and obesity management.
“It took a long time for us to realize that this really was something,” Holst told Healio. “It is only the recent successes of the GLP-1 receptor agonists that have really underpinned this work.”
Holst, professor of medical physiology in the department of biomedical sciences and vice chair of the faculty of health sciences at the University of Copenhagen, has spent his career studying the regulatory peptides of the pancreas and the gut and their importance in the regulation of the functions of the gastrointestinal tract and metabolism, with a focus recently on the incretin hormones GLP-1 and GIP. Holst is credited with the discovery of GLP-1 as the gut hormone responsible for the glucose-induced gastrointestinal stimulation of insulin secretion. His work led to the introduction of new medications that are highly effective in helping to manage type 2 diabetes and obesity and reducing risk for vascular diseases.
For his achievements, Holst will receive the 2021 Banting Medal for Scientific Achievement at this year’s American Diabetes Association Scientific Sessions, which recognizes significant, long-term contributions to the understanding, treatment or prevention of diabetes.
Holst spoke with Healio about what first drove his interest in incretin hormones, how new therapies will soon dramatically change diabetes and obesity management, and his love for the piano.
Healio: What was the defining moment that led you to your field?
Holst: There were several, actually. When I started many years ago, I was a young doctor training in surgery. We had some patients who developed reactive, postprandial hypoglycemia after gastric surgery. We were interested in incretin and insulin secretion, and we speculated that something in the gut was responsible for this phenomenon. That is what I was trying to solve. It was a goal in the interest of the department and our research group. What are the responsible incretin hormones that could be causing this? It took about 25 years before we got our answer — GLP-1.
Healio: Have you ever been fortunate enough to be part of medical history in the making?
Holst: I attended the European Association for the Study of Diabetes annual meeting in Stockholm in 2015, when CV outcomes data for the SGLT2 inhibitor empagliflozin [Jardiance; Boehringer Ingelheim] were revealed for the very first time. That meeting was fantastic. People were shouting, standing on chairs. It was an unbelievable moment, and I will never forget it. I could not sleep the night after; it was so overwhelming to me. Then I thought: What is going to happen with my GLP-1 research? The next morning, I realized I should not worry too much.
The natural solution, of course, was to combine SGLT2 inhibitors and GLP-1 receptor agonists. That is, today, a very good idea. Eventually, when all the pharmaceutical companies can agree, this could be a possibility. Right now, it is not possible because it is too expensive, but eventually this will be a thing you can do. The two principles are very different, so they will be complementary medicines.
Our own discovery of a new insulin-releasing peptide from the gut — of course we were thrilled and excited and happy about it. Now we have solid evidence for CV benefits with GLP-1 receptor agonists; the latest developments with the newer agents like semgalutide 2.4 mg [Wegovy, Novo Nordisk] on body weight and the dual GIP/GLP-1 receptor agonist tirzepatide [Eli Lilly], with HbA1c falling below 5.7%, are unbelievable. After all of these years in the desert, so to speak, we are finally getting somewhere, where real change is going to happen.
Healio: What do you think will have the greatest influence on your field in the next 10 years?
Holst: No doubt, we are at the beginning of a completely new age of therapies for both obesity and diabetes. All of these discoveries are very new, and sometimes adjustments will be needed. How do people react, for example, when they all of a sudden lose 20% of their body weight in 20 weeks? We have to ask these people how it feels to experience such a change. We may have to dial therapies up and down a bit. That said, the idea that such change is even possible was once unheard of. We will have fantastic years to come.
Healio: What advice would you offer a student in medical school today?
Holst: First, congratulations. It is a fantastic area of study and a good choice. It covers such a broad field of biology and human relationships. There are so many things you can do with that education. Open your eyes; there are opportunities everywhere to make a difference. Nothing has been finished; nothing is static. Medicine will be rewarding, for all of your life.
Healio: What are your hobbies and interests outside of medicine?
Holst: Music is my main interest. I play the piano. I am not very good any longer, but I still love it. I have music in my ears, always. I know a lot of music. I am never without a bit of a tune in my ears. I don’t even need headphones; the music is there already.