The conversation around Semaglutide, known widely by brand names like Ozempic and Wegovy, has undeniably captured global attention. Initially developed as a groundbreaking treatment for type 2 diabetes, its remarkable effects on weight loss have propelled it into the spotlight, leading many to hail it with terms like ‘miracle’, ‘revolutionary’, and even ‘holy grail’. From Hollywood to Manhattan and now reportedly making its way through Westminster, the drug’s popularity for shedding pounds is hard to overstate.
Yet, amid the widespread enthusiasm and dramatic personal stories, a significant voice offers a more nuanced perspective – and a rather startling warning. This voice belongs to Professor Jens Juul Holst, a pioneering scientist whose foundational research into the hunger-regulating hormone GLP-1 in the 1970s directly paved the way for the development of Semaglutide and similar medications. He is uniquely positioned to discuss not just how these drugs work, but also their potential long-term impact on the human experience.
Professor Holst, based in the Department of Biomedical Sciences at the University of Copenhagen, reflected on the drug’s effects in an interview with Wired. His insights underscore that while the medication is incredibly effective at its intended purpose – regulating blood sugar and significantly suppressing appetite by mimicking GLP-1 – this efficacy comes at a considerable ‘price to be paid’. It’s a perspective rooted in decades of scientific inquiry into the very biological pathways these drugs modulate.
His central concern revolves around a potential side effect that transcends the physical and delves into the psychological and emotional realm. Professor Holst warned that patients might find it difficult to stay on the medication long-term because, for some, it could make life ‘so miserably boring’ that they simply wouldn’t tolerate it indefinitely. He posits that once you have been on the drug for a year or two, this profound lack of engagement could drive people back to their former habits and lifestyles.
The reason for this potential boredom, as explained by Holst, is fundamentally linked to the drug’s core mechanism: it significantly diminishes appetite and, crucially, removes the pleasure derived from eating. He stated plainly, “What happens is that you lose your appetite and also the pleasure of eating, and so I think there’s a price to be paid when you do that.” For individuals who genuinely enjoy food, who find joy in its taste or the social rituals surrounding meals, this loss of pleasure can be a significant detriment.
If you like food, then that pleasure is gone,” Holst explained. “The craving for food for some people is taken away when they take GLP-1 drugs.” This isn’t merely a suppression of hunger pangs; it’s a fundamental alteration in the relationship with something that is both a biological necessity and, for many, a source of considerable enjoyment and comfort. The prospect of food becoming merely fuel, stripped of its sensory and social rewards, is what leads Holst to predict that long-term adherence could be challenged by a feeling of pervasive tedium.
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The potential impact of these drugs might even extend beyond food. Emerging reports suggest that GLP-1 agonists could suppress other desires and compulsive behaviors. These include the urge to drink alcohol, smoke cigarettes, shop, or even bite one’s nails. This phenomenon points towards a broader influence on the brain’s reward circuitry, specifically dopamine pathways.
The theory is that by altering these pathways, GLP-1 drugs might lessen the dopamine ‘hit’ associated with various rewarding activities, not just eating. An article in The Atlantic described one woman’s experience on semaglutide as like a switch being flipped in her brain, extinguishing cravings and impulses, including the desire to shop or drink. While intriguing, it is important to note that the majority of the research supporting this broader effect on addiction and compulsive behavior has been conducted on animals, such as lab mice showing reduced desire for cocaine. More extensive human trials are necessary to confirm these effects and understand their full implications.
One critical concern tied to adherence is the issue of weight regain upon discontinuation of the drug. Research has shown that the effects often reverse when the medication is stopped. A trial published in April 2022 highlighted this, with participants who stopped taking semaglutide after 68 weeks regaining approximately two-thirds of the weight they had lost. This underscores that Semaglutide, for weight loss, appears to be a treatment that requires continuous use to maintain its effects.
Professor Holst himself doesn’t foresee a future where a vast segment of the population remains on these GLP-1 drugs for their entire lives. Citing the history of other GLP-1 medications, which have been available since 2005, he notes that patients typically haven’t stayed on them long-term for various reasons. A 2020 study on GLP-1 drug use for type 2 diabetes found that a significant 70 percent of patients stopped taking them within two years.
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“We don’t know why people stop taking these drugs, but we know for a fact that they do stop,” Holst told Wired. While the loss of interest in food is a potential factor he hypothesized, the reasons are likely multifaceted. Regardless of the cause, the pattern of discontinuation, combined with the risk of weight rebound, presents a complex challenge for long-term weight management using these medications.
Beyond the potential for existential boredom, these powerful drugs are not without their array of physical side effects. While often described as ‘mild-to-moderate’ in clinical trials, they can include nausea, dizziness, constipation, vomiting, and diarrhoea. More severe side effects have also been reported, such as hair loss and a gaunt facial appearance, colloquially termed “Ozempic face”, resulting from rapid weight loss.
In rare cases, more serious complications like renal failure, pancreatitis, and intestinal obstruction can develop. Gallbladder-related disorders, including gallstones, and pancreatitis were noted in the 2021 clinical trial results on semaglutide in obese adults, with nearly one in ten experiencing severe side effects, leading some to stop the medication.
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Concerns about side effects have grown to the point where experts are warning of a surge in Emergency Room visits linked to Ozempic and Wegovy use. ER doctors have reported seeing patients presenting with severe diarrhea, nausea, and bloating. Compounded or off-brand versions of the drug, which have become more prevalent due to high demand and shortages, are particularly cited in adverse event reports received by the FDA, raising alarms about their safety and effectiveness compared to approved medications.
The skyrocketing popularity of Semaglutide for weight loss has had another, deeply concerning consequence: national shortages of the drug for the very patients it was originally intended to treat – those with type 2 diabetes. Professor Holst highlighted the stark reality of this situation, drawing a sharp contrast between the use of the drug for cosmetic weight loss and its critical necessity for managing a severe, debilitating disease.
He urged people to consider the struggles faced by diabetes patients who cannot access needed medication. “Have you ever visited a diabetes hospital? It’s really deplorable,” he said, describing patients with amputated limbs, compromised cognitive function, heart problems, or who are severely mobility – impaired, miserable, and depressed. For these individuals, drugs like Ozempic are not about fitting into a smaller size; they are vital tools to prevent devastating complications and improve their quality of life.
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Amid the focus on pharmaceutical interventions, it’s fascinating to consider parallel research into natural compounds that might offer similar metabolic benefits. New research from the University of Arizona and the University of Vienna suggests that a specific type of fiber, beta-glucan, found abundantly in foods like oats and barley, could aid weight loss and blood sugar control in ways that echo Ozempic’s effects, but through entirely natural mechanisms.
Long overlooked, fiber is gaining recognition for its crucial role in gut health. The gut microbiome, teeming with trillions of bacteria, thrives on fiber. In the 2024 study, researchers observed mice on a high – fat diet supplemented with various fibers. Only beta – glucan led to weight and body fat loss within weeks, even without reduced food intake. This wasn’t just about feeding gut bacteria; it was about feeding them the right kind of fiber.
Beta – glucan, a soluble fiber, is easily fermented by gut microbes. Mice receiving beta – glucan saw elevated levels of Ileibacterium, a bacterium previously linked to weight loss. This fiber digestion produced butyrate, a gut chemical known to trigger the body’s natural release of GLP – 1 – the same hormone that Ozempic mimics. In essence, consuming beta – glucan could prompt your body to produce its own appetite – regulating, blood – sugar – controlling hormone.
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The benefits of butyrate extend further, potentially improving gut lining health, supporting liver function, and reducing inflammation, all contributing to overall wellness. Foods like oats, barley, sorghum, rye, maize, triticale, wheat, durum wheat, rice, mushrooms, and seaweed are excellent natural sources of beta – glucan. While this research in mice is incredibly promising and points towards exciting dietary approaches, the critical next step, as always, is confirming these effects through human trials.
The application of GLP – 1 agonists is also expanding to younger populations. In 2023, the American Academy of Pediatrics issued its first clinical practice guideline for evaluating and treating children and adolescents with overweight and obesity. These guidelines included the consideration of GLP – 1 receptor agonists, alongside bariatric surgery and other medications, for eligible young people.
Experts like Melanie Cree, an associate professor of pediatric endocrinology, emphasize the importance of intervening early. Helping a child lose excess weight before puberty can significantly reduce their risk of developing type 2 diabetes, a condition that tends to be more aggressive in teenagers than in adults. Caroline M. Apovian, a professor at Harvard Medical School, explains that GLP – 1 agonists work similarly in teenagers as they do in adults, adjusting the body’s naturally produced hormones to stimulate insulin release, reduce appetite, slow digestion, and increase fullness.
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Clinical trials support the potential benefits in younger patients. A 2022 study in The New England Journal of Medicine reported that adolescents with obesity or overweight and a weight – related condition, who received weekly semaglutide injections, lost an average of 16 percent of their body weight over 68 weeks. More recently, a September 2024 study in The New England Journal of Medicine on an older GLP – 1 agonist, liraglutide, found that it reduced BMI by an average of 6 percent in children aged six to 11 with obesity. These findings offer hope for managing childhood obesity, which is crucial for long – term health.
However, using these powerful medications in developing bodies presents unique challenges. Dr. Cree notes that the drugs don’t work for everyone, failing in about one in four children, potentially due to hormonal changes during puberty and higher growth hormone levels causing insulin resistance and increased hunger. Despite these hurdles, personal stories like that of Arrellin, a high school sophomore who lost 40 pounds on Wegovy, highlight the profound positive impact weight loss can have on a young person’s confidence, energy, and overall well – being.
The scientific story of GLP – 1 agonists like Ozempic and Wegovy is still being written. From their origins in diabetes research, pioneered by scientists like Professor Holst, to their widespread use for weight loss and potential application in children, the narrative is one of significant medical advancement. Yet, Professor Holst’s candid warning about the potential long – term ‘boring’ reality, coupled with the practical challenges of side effects, adherence, and accessibility for those who need it most, adds crucial layers of complexity.
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As we navigate this new era of powerful metabolic interventions, it becomes clear that the path to health is rarely simple. While pharmaceutical breakthroughs offer incredible tools, they come with considerations about long-term use, quality of life, and equitable access. Simultaneously, fascinating research into natural dietary approaches like beta-glucan reminds us that our relationship with food and our bodies is a dynamic, intricate system with many potential points of intervention, both cutting-edge and ancient. The journey toward healthier lives involves exploring all these avenues with open eyes, balancing the exciting possibilities with a clear-eyed understanding of the costs and challenges.
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