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In this episode of Longevity by Design, Dr. Gil Blander welcomes Dr. Jens Juul Holst, a renowned Danish physician and physiologist, to discuss GLP-1, a hormone transforming our understanding of metabolic health. Dr. Holst, who discovered and described GLP-1, explains its role as a gut-derived hormone that regulates appetite, insulin secretion, and digestion, offering a groundbreaking approach to managing obesity and type 2 diabetes.
The conversation explores how GLP-1 receptor agonists, have evolved into powerful medications. These drugs help patients achieve significant weight loss, reverse diabetes, improve cardiovascular health, reduce inflammation, and potentially enhance cognitive function. Dr. Holst delves into their long-term implications for preventing diabetes, extending health spans, and even reducing the risks of obesity-related cancers and improving fertility.
Dr. Holst emphasizes that while GLP-1 offers life-changing benefits, sustainable health still hinges on balanced diets and regular physical activity. This episode provides a fascinating look at the intersection of science, medicine, and lifestyle in promoting longevity.
Episode highlights:
- Introduction: 00:00:00
- What is GLP-1: 00:03:00
- what is a GLP-1 agonist: 00:04:15
- what are the target organs of the GLP-1 agonist?: 00:06:30
- what is the effect of the GLP-1 agonist on a diabetic patient?
: 00:10:00 - What percentage of a diabetic patient on GLP-1 have complete remission: 00:11:30
- How long did it take to bring a drug to market from the moment you first discovered it: 00:23:30
- What is the GLP-1 effect on cognition and dementia: 00:29:00
- GLP-1 effect on kidney diseases: 00:32:00
- GLP-1 positive effect on fertility: 00:35:00
- GLP-1 positive effect on cancer: 00:37:30
- Should a patient be on GLP-1 for life: 00:41:00
- GLP-1 related side effects: 00:48:00
- GLP-1 effect on resting heart rate: 00:52:30
- GLP-1 related side effects: 00:48:00
- GLP-1 from Lilly vs novo nordisk: 00:55:00
- GLP-1 oral versus the injectable: 00:58:00
- GLP-1 effect on lifespan: 01:00:30
- GLP-1 effect on lifespan: 01:00:30
- What led you to become a scientist: 01:03:00
- The story of discovering the GLP-1: 01:04:30
- How did you successfully extend the half-life of the GLP-1 agonist: 01:09:00
- GLP-1 moving from once a day to once a week: 01:16:00
- Top tip to improve healthspan: 01:18:00
GLP-1 Agonists: A Game-Changer for Diabetes and Obesity
Dr. Jens Juul Holst explores the revolutionary impact of GLP-1 agonists in treating diabetes and obesity. These medications mimic a natural gut hormone to regulate insulin secretion, appetite, and weight. Through their ability to normalize blood glucose levels and promote significant weight loss, GLP-1 agonists have transformed the lives of patients with type 2 diabetes and obesity. Holst highlights their success in enabling over 50% of diabetes patients to achieve normal glucose levels while addressing the systemic health risks tied to obesity. This innovation represents a monumental leap in metabolic disease management.
Beyond Weight Loss: Cardiovascular and Inflammatory Benefits of GLP-1
Dr. Holst emphasizes the additional health advantages of GLP-1 agonists, beyond their effects on diabetes and obesity. These drugs improve cardiovascular outcomes by reducing major adverse events such as heart attacks and strokes. They also decrease systemic inflammation, a common issue in metabolic diseases. Holst points out that GLP-1 therapy’s dual action on vascular health and inflammation positions it as a comprehensive solution for improving long-term health outcomes in patients with diabetes or obesity.
A Journey of Discovery: From Gut Hormones to Weekly Injections
Dr. Holst reflects on the multi-decade journey from the discovery of GLP-1 in 1986 to its current use as a weekly injectable drug. Early hurdles included the hormone’s rapid degradation in the body, which was resolved through innovative molecular engineering to extend its half-life. These advancements led to more convenient dosing and enhanced effectiveness, enabling weight loss of up to 18%. Holst highlights the collaborative efforts behind this progress, demonstrating how basic scientific research can evolve into life-changing treatments for millions of patients.
The Potential of GLP-1 for Cognitive Health
Dr. Holst discusses emerging evidence supporting the role of GLP-1 agonists in enhancing cognitive function and reducing the risk of dementia. He highlights ongoing studies that indicate GLP-1 therapies may improve cognitive impairment and decrease the risk of Alzheimer's disease. These effects are attributed to the drugs’ influence on reducing inflammation and improving vascular health in the brain. Holst emphasizes the potential for GLP-1 therapies to address neurological conditions in addition to metabolic diseases, broadening their application and impact.
“There are fantastic effects now on the brain. One is cognitive impairment that will be improved. That was already very nicely shown with the original compound…The first reports now on Alzheimer's disease have come out with a very, very, very strong effect.”
The Challenges of Widespread GLP-1 Usage
Dr. Holst highlights the challenges patients face with GLP-1 therapy, particularly regarding long-term use. He explains that discontinuing therapy often leads to weight regain due to the loss of appetite regulation. Holst also discusses potential strategies for maintaining weight loss after stopping the drug, such as lifestyle changes and lower doses during maintenance phases. These approaches aim to reduce the reliance on medication while promoting sustainable health improvements.
“If you stop, then you cannot reduce your appetite any longer, and you will be hungry, and you will start eating more. And that’s exactly what happens if you terminate the therapy, and that’s been demonstrated in several studies.”
The Development of Long-Acting GLP-1 Therapies
Dr. Holst reflects on the advancements in GLP-1 therapy development, particularly the transition to long-acting injectable formulations. He explains how molecular modifications, such as adding fatty acid chains, increased the drug’s half-life, allowing for weekly injections. This development has significantly improved patient compliance and outcomes, particularly for those requiring consistent weight loss and glucose control.
“They put a fatty acid chain to the GLP-1 sequence, and then yes, it worked…The half-life in the weekly injection is almost a week, so they have really long-acting compounds now.”
The Impact of GLP-1 on Fertility
Dr. Holst explores GLP-1’s surprising potential in fertility treatments, particularly for individuals with metabolic-related infertility issues, such as polycystic ovary syndrome (PCOS). He explains that improving metabolism and reducing insulin resistance with GLP-1 therapy can enhance fertility outcomes for both men and women. Although he urges caution due to limited long-term data, Holst notes the promising effects observed in clinical experiences.
“If you can ameliorate the metabolism of these individuals, they will immediately become pregnant. And we knew that already. You can even do it with metformin…Once GLP-1s were introduced, it turned out that yes, these people became pregnant.”
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