Latest news with #DanielDrucker

From Lab to Landmark Therapy: Meet the Woman Behind GLP-1

Medscape

2 days ago

Health
Medscape

From Lab to Landmark Therapy: Meet the Woman Behind GLP-1

Svetlana Mojsov, PhD Biochemist Svetlana Mojsov, PhD, has been awarded the Frontiers of Knowledge Award in Biology and Biomedicine, presented by Spain's BBVA Foundation, for her collaborative research with Daniel Drucker, Joel Habener, and Jens Holst. Their work revealed the biological function of the hormone GLP-1, a key regulator of glucose metabolism and appetite. These discoveries paved the way for a new generation of therapies that have transformed the management of type 2 diabetes (T2D) and obesity, offering not only improved glycemic control and weight loss but also reduced cardiovascular risk. The findings have also sparked new lines of basic and translational research in multiple disease areas. Speaking to El Médico Interactivo , a Medscape Network platform, during the recent awards ceremony in Bilbao, Spain, Mojsov shared her perspective on the future of research. 'We are witnessing a new paradigm in which clinical experience is guiding future research to help us understand very fundamental concepts,' said Mojsov, currently a research associate professor at Rockefeller University in New York. How does it feel to see that drugs derived from your GLP-1 research are helping millions of people manage diabetes and obesity? I'm very happy to have contributed to something that has helped so many people. These drugs improve not only health outcomes but also overall quality of life. Being a scientist is a profession with many rewards — and certainly more benefits than setbacks — when your work can make a real difference. All scientists are driven by the goal of advancing knowledge and human health. I feel privileged to have been part of the early stages of this long scientific journey. Over the past two decades, GLP-1-based therapies have represented a major breakthrough in the treatment of T2D and obesity, improving both quality of life and clinical outcomes for millions of patients. For the first time, we've seen body weight reductions of up to 20% — which is particularly important because excess weight worsens the prognosis of T2D. Most earlier treatments actually caused weight gain, which limited their effectiveness. GLP-1 therapies, in contrast, help patients lose weight and improve disease outlook at the same time. What led you to investigate gut hormones, particularly GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)? My interest in peptide-based therapies for glucose metabolism goes back to the mid-1970s, when I was a graduate student working with Dr Bruce Merrifield at Rockefeller University. We were studying the biology of glucagon — a hormone that raises blood glucose — and exploring how to synthesize glucagon analogs and inhibitors using solid-phase peptide synthesis. At that time, however, the available synthesis techniques often produced biologically inactive glucagon due to chemical modifications in the amino acid sequence. Merrifield encouraged me to develop new strategies to overcome this limitation, which laid the foundation for my later work on GLP-1. Were these the strategies you went on to explore in your research? Yes. For my doctoral thesis and later during my postdoctoral work, I focused on the amino acid sequence and biology of glucagon. That experience was instrumental in my discovery of GLP-1 in the early 1980s at Massachusetts General Hospital in Boston. In 1983, I identified the biologically active form of GLP-1 as a 31-amino acid peptide, which I named GLP-1 (7-37). I also hypothesized that it functioned as an incretin, a gut-derived peptide that stimulates insulin secretion in response to food intake. You and the other three awardees worked on the same hormone. Did you collaborate directly, or was the work conducted independently? How important is collaboration in this field? To detect GLP-1 (7-37) in the gut, I synthesized it myself in the endocrinology unit of my lab using solid-phase peptide synthesis. I also developed highly specific antibodies, radioimmunoassays, and chromatographic techniques that allowed me to confirm the presence of GLP-1 (7-37) at the site of incretin secretion. Although I conducted this initial work independently as a chemist, that kind of foundational research still requires close collaboration across disciplines. After identifying GLP-1 (7-37), I began working closely with Drs Joel Habener and David Nathan at Massachusetts General Hospital, and with Dr Gordon Weir at the Joslin Diabetes Center. So yes, throughout my work, I collaborated extensively with both biologists and clinical researchers. Your first GLP-1 findings date back to 1986. The first drugs came in 2005, and those widely used today appeared in 2017. Has the translation from discovery to clinic taken too long? What could be done to accelerate this process? You're right. Our early clinical studies with Nathan were the first to demonstrate that GLP-1 (7-37) stimulates insulin secretion and lowers blood glucose in people with T2D, establishing its therapeutic potential. Back at Rockefeller, my colleague Yang Wei and I showed that GLP-1 receptors are expressed not only in the pancreas but also in the brain, heart, and kidneys. This indicated that GLP-1's effects across these organs are mediated by a common receptor. In the 1980s and 1990s, the pharmaceutical industry was skeptical that peptides could become viable drugs because they required injection, and oral medications were strongly preferred by patients. Still, GLP-1 (7-37) held promise. In 2005, researchers discovered a longer-acting GLP-1-like peptide in lizard venom, which allowed Amylin Pharmaceuticals to act quickly since they didn't have to develop a new compound from scratch. That said, many companies were hesitant to invest in a peptide derived from a lizard. Twenty-five years after my original publications, Novo Nordisk and Lilly launched long-acting GLP-1 analogs. These drugs are now used to treat a wide range of conditions beyond T2D and obesity, including cardiovascular and renal disease and potentially even neurodegenerative disorders. It's the first time a single drug class has shown such broad therapeutic utility. Your discoveries are already benefiting millions of patients with obesity and diabetes, but cost remains a significant barrier. Do you think these drugs will become more accessible in low- and middle-income countries? They must become more affordable — otherwise, their usefulness is fundamentally limited. The broader the access, the greater the public health impact. I'm optimistic that continued innovation will help lower costs and improve global accessibility. These therapies shouldn't be reserved only for patients in wealthy nations. The health benefits must be shared more equitably. We also need to prioritize and protect scientific research. Especially given the current climate in the US, it's worth remembering that our longer, healthier lives are built on scientific progress. While the pharmaceutical industry plays a vital role, it all starts with discovery — and discovery starts in academic and research institutions. That's where we need to focus our support. Novo Nordisk did outstanding work, but they built on foundational research that came from the lab. Ultimately, we all have to work together. Every breakthrough starts with knowledge— knowledge, knowledge, and more knowledge. With T2D and obesity rising globally, and GLP-1 therapies now widely available, do you worry that they might shift attention away from prevention? No, quite the opposite. These therapies are most effective when combined with a commitment to overall health. Although some health conditions are unavoidable, I believe these drugs serve as a reminder of the importance of personal well-being. They help people take concrete steps toward better health. GLP-1 receptor agonists are now a key part of the pharmacologic toolkit for managing obesity and diabetes. Do you think they'll prove effective in other conditions, such as cardiovascular disease, neurodegeneration, or addiction? We already know they offer cardiovascular benefits, and physicians are prescribing them for people with diabetes — including those on insulin — because they also support kidney function. So these therapies are already broadly accepted and widely used. When it comes to neurodegenerative diseases, however, it's still too early to draw conclusions. Current findings are anecdotal and based on small patient cohorts. We need a much better understanding of the mechanisms involved. The same applies to addiction. There's speculation that GLP-1 analogs might help prevent addictive behaviors, but we need robust evidence before reaching that conclusion. This is the exciting part of science: knowledge opens the door to new discoveries. We need to return to the lab, use animal models, and uncover the mechanisms at work. Once we do, we'll be in a better position to confirm the full range of effects and explore new indications. You've had to fight for recognition on five patents. Do you believe being a woman made that more difficult? And do young women entering science today have equal opportunities? I grew up in Yugoslavia, where we weren't really taught to think in terms of gender differences. I never believed someone would take advantage of me for being a woman. Whether it happened or not, I can't say, but I never attributed any setbacks to my gender. I knew what I wanted and I fought for it. I pursued the patent issue because the original filing didn't properly reflect my contribution. My work resulted in five patents—four of which I secured after correcting Massachusetts General Hospital's initial application. Today, women are firmly part of the scientific community. Half of all researchers are women, so there should be no room for discrimination. That said, when something isn't right, we must speak up—clearly and confidently—and have the courage to stand our ground. Your perseverance and discipline are admirable. How important are those traits for aspiring researchers? They're both essential. This path is never easy.

Could China's New GLP-1 Drugs Beat Out Ozempic?

Scientific American

01-07-2025

Health
Scientific American

Could China's New GLP-1 Drugs Beat Out Ozempic?

A drug that outperforms placebo in helping people to lose weight is one of a growing number of next-generation obesity drugs being produced in China. At first, Chinese pharmaceutical companies rushed to make similar versions of blockbuster weight-loss drugs, such as Wegovy and Ozempic, that have taken the world by storm. Nowadays, China is emerging as important innovator for new drug discovery in this field, says Daniel Drucker, an endocrinologist at the University of Toronto in Canada. Results from a phase III trial of ecnoglutide show that people receiving a weekly injection of the drug lost up to 13.8 kilograms over 48 weeks of treatment. By contrast, people given placebo injections lost around 200 grams. The results were published in The Lancet Diabetes and Endocrinology on 21 June. On supporting science journalism If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. Ecnoglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist analogue, similar to the blockbuster obesity drug semaglutide. These drugs mimic the hormone GLP-1, which is involved in regulating appetite and managing blood-sugar levels. Unlike semaglutide, ecnoglutide preferentially targets the production of cyclic adenosine monophosphate, a messenger molecule associated with regulating glycogen, sugar and lipid metabolism, which helps to control blood-sugar levels, as well as weight loss. The study, funded by drug manufacturer Sciwind Biosciences, based in Hangzhou, China, included 664 people given either a weekly injection of a placebo, or one of three doses of ecnoglutide. At the maximum dose of 2.4 milligrams, 92.8% of people lost at least 5% of their body weight, compared with 14% of people receiving placebo injections. People receiving ecnoglutide were also able to maintain their reduced weight after stopping treatment, regaining around 1% of their body weight over a 7-week period. Linong Ji, a co-author and a diabetes researcher at Peking University People's Hospital in Beijing, says ecnoglutide also improved risk factors for heart disease and diabetes, and reduced the amount of fat in people's livers. More drugs to come Dozens of GLP-1 drugs are being developed and tested in China, with 'many more to come', says Drucker. Among them is mazdutide, which mimics GLP-1 and glucagon, a hormone involved in blood-sugar levels. In trial results published in May, a weekly injection helped more people to lose up to 15% of their body weight over 36 weeks and reduced the risk of cardiovascular diseases compared with a placebo treatment. Developed by Eli Lilly in Indianapolis, Indiana, mazdutide is manufactured by Innovent Biologics in Suzhou, China, under an exclusive licence. Other trials are testing whether the drug can treat sleep apnoea or type 2 diabetes. The growing number of new GLP-1 drugs target multiple pathways at the same time so will result in more-tailored treatments, says Sof Andrikopoulos, a diabetes researcher at the University of Melbourne. The next generation of drugs will target specific conditions associated with diabetes and obesity, such as sleep apnoea, fatty liver disease, chronic kidney disease and heart disease, he adds. 'It'll give us options and it will make personalized medicine in obesity and diabetes more accessible.' Triple threat Another drug being developed in China, known as UBT251, is a triple agonist, mimicking GLP-1, glucagon and another hormone called gastric inhibitory polypeptide (GIP), which is involved in fat metabolism. UBT251 is the first biweekly injectable GLP-1 medicine and is in the early stages of testing to achieve weight loss and treat chronic kidney disease, fatty liver disease and type 2 diabetes. In March, Hengqin-based manufacturer the United Laboratories entered into a US$2-billion deal with Danish firm Novo Nordisk, which developed semaglutide, giving Novo Nordisk exclusive rights to test and sell the drug outside the Chinese mainland, Hong Kong, Macau and Taiwan. Bofanglutide, developed by Gan & Lee Pharmaceuticals in Beijing, is another biweekly injectable treatment, but it targets only GLP-1. A phase II trial began enrolling US participants with obesity in March to test it against a placebo and tirzepatide — sold as Mounjaro and Zepbound by Eli Lilly. Andrikopoulos says it makes sense that China is developing these drugs. 'Obesity and diabetes are major problems in Asian populations in China and in India,' he says. Studies that recruit participants in China are also important for investigating the efficacy of GLP-1 drugs in Asian populations, which could reveal differences not observed in studies from Europe or the United States. A Hong Kong-based pharmaceutical company, Ascletis, is also investigating the benefit of once-daily oral drug, called ASC30, for weight loss. Early trial results show that participants lost 6% more of their body weight on the drug than with a placebo. The company has applied for permission from the US Food and Drug Administration to run a phase II trial. Novo Nordisk and Eli Lilly are also working on oral GLP-1 medicines.

Beyond Ozempic: Why metabolic health management needs to be about more than just weight

Toronto Star

01-05-2025

Health
Toronto Star

Beyond Ozempic: Why metabolic health management needs to be about more than just weight

This spring, Toronto endocrinologist Dr. Daniel Drucker was awarded the prestigious Breakthrough Prize in Life Sciences — the 'Oscars of science' — for a discovery he made nearly four decades ago. While working in a Boston lab in the 1980s, Drucker helped unravel the therapeutic potential of GLP-1, a gut hormone involved in blood sugar regulation. Ten years later, he built on that research by demonstrating how this naturally occurring peptide could also suppress appetite, laying the groundwork for a class of drugs that are now reshaping weight management and obesity treatment. Originally developed to treat Type 2 diabetes, GLP-1 receptor agonists or GLP-1 RAs — better known by such brand names as Ozempic, Wegovy and Mounjaro — have become widely known for their use in weight loss. In 2023 alone, 7.1 million prescriptions were dispensed in Canada. However, while GLP-1 RAs are a powerful tool, they're not meant to be taken in isolation. In 2020, Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons developed a set of patient-centred, experience-based best practices designed to guide health-care providers in delivering obesity care. These guidelines emphasize that effective obesity treatment should include medical nutrition therapy (essentially, a personalized dietary plan created by a registered dietitian), physical activity, psychological interventions and other behavioural adaptations. Yet the reality of obesity care, and health care in general, presents challenges that leave many patients without adequate support.

Canadian scientist wins Breakthrough Prize for discovery of hormone used in Ozempic, Mounjaro

CBC

07-04-2025

Health
CBC

Canadian scientist wins Breakthrough Prize for discovery of hormone used in Ozempic, Mounjaro

A Canadian researcher has won a 2025 Breakthrough Prize in Life Sciences for discovering the GLP-1 hormone used in diabetes and obesity medications — including Ozempic, Wegovy and Mounjaro — that have changed the lives of millions of people around the world. Dr. Daniel Drucker, an endocrinologist and a clinician-scientist at the University of Toronto and the Lunenfeld-Tanenbaum Research Institute at Sinai Health, shares the $3 million US prize with four colleagues from the United States and Denmark. They were all involved in the development of the now-famous drugs manufactured by Novo Nordisk and Eli Lilly. Drucker and three co-winners made discoveries about glucagon-like peptide-1 in their labs. The other recipient of the award, Lotte Bjerre Knudsen, who works for Novo Nordisk, led the way in developing it into medications. The Breakthrough Prizes, often referred to as the "Oscars of Science," were handed out Saturday in Los Angeles for categories including fundamental physics and mathematics, in addition to life sciences. The Breakthrough Foundation says the prizes were created to "celebrate the wonders of our scientific age." Another Canadian, Maaike van Kooten of National Research Council Canada, shared a $100,000 US prize called New Horizons in Physics with two international colleagues for work in optics to view exoplanets. In an interview in the week prior to the event, Drucker said the prize is meaningful because it's awarded by other scientists and "gets a lot of attention in the scientific community." "We have students and trainees and awards like this tell them that the world is watching and thinks the work is meritorious. And I think that's just great for morale and for young people," he said. Drucker began his journey studying genetic sequencing of glucagon-like peptides at a lab in Boston in the 1980s, then returned to Canada and continued his work at the University of Toronto. He spoke with The Canadian Press about those early days, what he thinks about how the resulting medications have changed the world's view of obesity and what other health issues GLP-1 might address in the future. This interview has been edited for length and clarity. When you started at that lab in Boston, why were you studying this particular hormone? "There were probably about a dozen projects in the lab at that time. So some people were working on pituitary hormones. Some people were on basic cell biology projects. Other people were working on different genes and glucagon was one of the projects in the lab.... It just so happened when I got there, they said, 'OK Drucker, you work on the glucagon gene.' [It] could have been another gene [and] you never would have heard from me again. Were there any key moments where you thought, 'Wow, this is a big deal?' "I don't think there was any one 'Eureka!' moment, but I will say the potential importance dawned on me when I walked into the lab one day and my notebooks were gone. And I said, 'Oh my gosh, someone broke into the lab and stole my notebooks.' And then it turned out no — my supervisor [and a fellow prize winner], Joel Habener, took my notebooks because he was excited enough about the results to file a patent." When did you come to the University of Toronto? "I came back in 1987.... In 1996, when we and others discovered that GLP-1 inhibits food intake, that was in my lab in Toronto, and we've done experiments on heart disease and inflammation and kidney disease and liver disease. So I literally have been working on this for 40 years." When did Novo Nordisk (manufacturer of Ozempic and Wegovy) become involved? "I think the big companies, Novo Nordisk and Eli Lilly, and even other companies were trying from the beginning to develop medicines based on GLP-1. But we learned through some painful lessons that if you give too much GLP-1 too quickly, people throw up. It's still a side effect today, right? Some people just don't feel well and they have some nausea and vomiting. And so it took the pharmaceutical industry quite a while to figure out how to make GLP-1 last longer so it's not broken down, how to give small amounts to start off with, how to slowly build up the dose, et cetera. And that took years to do." What are you working on now and what are some other applications for GLP-1 drugs? "If we just look in the last couple of years, beyond lowering blood sugar and beyond reducing body weight, we have seen that these medicines reduce the rates of heart attacks and strokes and reduce the rates of diabetic kidney disease and are helpful for people with obstructive sleep apnea and reduce disability in people with arthritis and prevent the development of severe metabolic liver disease. And there are trials underway in Parkinson's disease, in Alzheimer's disease, in substance use disorders. "So I kind of look at this and I go, 'Wow, how does that happen? What are the things that GLP-1 is doing in the brain or in the blood vessels or in the kidney to improve the health of these organs?' So we're really focused on this aspect of GLP-1, including how GLP-1 reduces inflammation, which we think is a major part of the benefits that GLP-1 brings to the table." Are cardiovascular benefits because GLP-1 medication reduces weight or manages diabetes and that improves cardiovascular health? "What we're starting to see is that in many of the trials, the benefits don't strictly correlate with weight loss or blood sugar control. So there's no question [that] getting your blood sugar normal if you have Type 2 diabetes, reducing your body weight if it's too high, that's helpful. "But when we actually look at the trials and we see who has the benefit and who doesn't, there's not a perfect correlation with blood sugar control or weight loss. And so we think there are, you know, independent actions of GLP-1, perhaps through reduction of inflammation, that are also beneficial. And this is exactly what we try and study in the lab." We're now seeing a culture shift in how we view obesity. What do you make of that? "It's a very complex discussion. So let's say 10 years ago, we had a very understandable movement, which was 'healthy at any size.' Don't focus on your weight per se, focus on your health, which I still think is a very powerful message. And part of that messaging was because we didn't have solutions other than bariatric surgery to allow people to become healthier, perhaps at a lower body weight.... And in society, there tends to be a segment of our society that looks at people living with obesity and says, 'Well, you know, it's just willpower. If you really wanted to lose weight, you could, you're just not trying' or 'You're lazy,' or you know, 'You're weak.' "And we know that many of these people that we see in clinical practice have been on very calorie-reduced diets and working out and doing everything that we asked them to do. But their brains are defending a higher body weight.... And now with the GLP-1 medicines, we see that... we can help people lose weight. And I think this is very powerful because the people who were struggling before who could not do it by themselves can now lose 10, 15, 20, 30, 50 pounds." Do you have any trepidation or thoughts about these drugs being used by people who may not need them? "Well, you're speaking to the person who worries about everything, so of course I have concerns... It's been a little bit like The Hunger Games. People have to phone six pharmacies and find one that had a month's worth of drugs and then drive as fast as they could to that drugstore to get them, which is not great. And so while that's happening, to see other people getting a prescription because Uncle Harry's wedding is coming up in two months and they just want to lose a little bit of weight so they can look a little more fit at Uncle Harry's wedding — you know, as a physician, I say, 'Wait a sec, this person living with heart disease and Type 2 diabetes needs these medicines to reduce the risk of heart attacks and strokes. Maybe that should be a priority as a society over you looking a little better for Uncle Harry's wedding.' So that's been one dilemma. "And then the other big challenge that we still have is these medicines are very expensive. In many jurisdictions, we don't have everyone with access to a drug plan. We don't [have] every drug plan agreeing to reimburse for the medicines. "And finally... we don't have clinical trials on healthier people without diabetes, without a higher body weight that are studied [to know], 'Well, are there any particular side effects in this group of individuals?' They weren't studied in the clinical trials. Is there something we should be worried about, going on and off the drugs when you want to lose that healthy? We don't know. And so we have to always be mindful of what we don't know about the safety of these medicines."

Yahoo