Hailed as Hollywood's best-kept weight loss secret, GLP-1 agonist drugs have dominated news stories and dinner table conversations this year [1].
As the number of individuals taking these drugs (through both prescription and off-label use) continues to rise, our understanding of their efficacy continues to evolve. But how safe are GLP-1 agonists, and are there more insidious aspects to this conversation that no one is talking about?
GLP-1 agonists in action: what are they, and how do they work?
GLP-1 agonists are drugs that have been designed to mimic the natural hormone glucagon-like peptide 1 (GLP-1), just like a perfectly fitting key copy. When these drugs are taken, they act like GLP-1 and seamlessly fit into hormone receptors in our body to elicit various downstream effects, including regulating blood glucose and curbing hunger.
Under normal conditions, GLP-1 hormone is naturally released by the gastrointestinal tract in response to eating [2]. It attaches to specific receptors found on many cells throughout the body, triggering four main biological effects:
- Activates satiety signaling in both the brain and gut. GLP-1 directly and indirectly sends signals to the brain to help your body recognize when it's full and no longer in need of further food intake [3].
- Increases insulin release and decreases glucagon release, and the combined effect of this modified hormone balance and chemical environment regulates the amount of glucose in the blood, preventing unhealthy spikes in blood sugar [4].
- Promotes the health of pancreatic beta cells, which improves the function of the pancreas, increasing the effectiveness of future insulin responses and leading to better blood sugar regulation [5].
- Slows down the digestion process, keeping food in the stomach for longer, which allows nutrients to be absorbed more slowly and prevents rapid increases in blood sugar after meals. It also reduces the body’s urge to eat more — meaning that you’ll eat less [6].
Semaglutide, sold under various brand names like Ozempic, Wegovy, and Rybelsus, is the active ingredient in GLP-1 agonist drugs that replicates the natural effects of the GLP-1 hormone [7].
Unlike the short duration of action of the naturally produced hormone, the synthetic drug version remains active for several hours or even days, resulting in a powerful and potent impact on metabolic regulation and appetite suppression [8].
The significant reduction in hunger sensations induced by GLP-1 agonists has resulted in their misuse by some celebrities and individuals who are seeking non-medical weight loss for appearance-focused and beauty-driven reasons. These individuals pay significant amounts of money out of pocket (meaning they do not have a prescription from a medical professional) to obtain these drugs, which limits access for patients who are prescribed GLP-1 agonists for medical reasons.
Addressing these issues and raising awareness about the risks involved is crucial to ensure the safe and appropriate use of semaglutide, particularly among healthy individuals who may be tempted to pursue drastic weight loss for aesthetic purposes.
Who are GLP-1 agonists recommended for?
GLP-1 agonists are not a recent addition to the pharmaceutical arsenal. They've been prescribed to patients with type 2 diabetes since 2005, addressing the metabolic imbalances that define this condition [9].
Scientists have understood for some time that individuals with diabetes frequently experience disrupted GLP-1 effects, meaning they struggle to regulate their blood sugar levels effectively, potentially contributing to the development of the disease [10]. As a result, GLP-1 agonists serve as a powerful intervention to correct this hormonal signaling and keep glucose levels and insulin response in range.
Strong evidence supports the effectiveness of GLP-1 medications in treating type 2 diabetes. A 2014 review of 15 studies showed that combining GLP-1 medication with insulin led to better glycemic control, and a 2016 meta-analysis of 78 studies confirmed the significant blood sugar-lowering effects of GLP-1 receptor agonists compared to a placebo [11, 12].
The direct effects of GLP-1 agonists on blood sugar control, coupled with their appetite-suppressing properties, aid in weight reduction by regulating calorie intake and reducing food consumption. Preventing overeating and reducing excess body fat results in a healthier metabolic profile and a reduced risk of high blood pressure, heart disease, and stroke.
This approach not only decreases the reliance on other diabetes medications like metformin or insulin, but also reduces the need for additional pharmaceutical interventions for related conditions that often manifest as a result of uncontrolled diabetes, such as statins for cardiovascular disease, or ACE inhibitors for kidney disease.
Targeting obesity, often the underlying driver of many chronic conditions, minimizes the use of additional drugs which may significantly enhance the quality of life for these patients.
Amidst the ongoing obesity epidemic and metabolic health crisis, are GLP-1 agonists the long-awaited saviors we desperately seek? Or does this debate overshadow the underlying causes of these pervasive societal issues, allowing profit-driven corporations with notable conflicts of interest to thrive at our collective detriment?
What are the issues associated with GLP-1 agonists?
Short-term
In the management of acute conditions, pharmacology plays a crucial role. Given the severe cardiometabolic risks associated with uncontrolled type 2 diabetes and excess body weight, timely intervention, and treatment in the short-term are essential for addressing these serious, and in some cases life-threatening, situations [14].
The escalating use of GLP-1 agonist drugs has resulted in increased demand and a decreased supply, as many off-label prescriptions are being written for individuals seeking quick weight loss without medical necessity. This has caused reported shortages in pharmacies, creating challenges for many patients who genuinely need these medications to manage chronic conditions [15]. Furthermore, uninsured patients and those without a prescription can expect to pay between $170-342 per week, contributing to the widening of the ever-present health disparities in the US [16].
But what about side effects?
Nausea, vomiting, and potential links to pancreatitis and diabetes complications have been reported with the use of GLP-1 agonists [17, 21]. Another alarming concern is the significant loss of lean muscle experienced by many patients on semaglutide drugs due to chronic calorie and nutrient restriction [18].
This dramatic shift in body composition can have negative health consequences such as impaired immune function, accelerated aging, compromised brain function, and a decreased metabolism. To mitigate this, it is crucial for individuals prescribed semaglutide to engage in resistance training and consume plenty of protein-rich foods to preserve muscle mass during treatment.
Additionally, new research raises serious concerns about GLP-1 agonist drugs and their effects on gastrointestinal health. A study published in early October 2023 compared new users of semaglutide or liraglutide with another weight loss agent, bupropion-naltrexone, which is not a GLP-1 agonist [22]. Among the 4,144 liraglutide, 613 semaglutide, and 654 bupropion-naltrexone users involved in the study, participants using the GLP-1 agonists experienced a marked increase in risk of developing gastrointestinal conditions compared to bupropion-naltrexone users, including:
- A 9-fold increase in pancreatitis.
- A 4-fold increase in bowel obstruction.
- A 3.7-fold increase in gastroparesis (also known as stomach paralysis, where your stomach doesn’t empty its contents properly). Another 2021 case report examined two individuals who developed medication-induced gastroparesis after beginning semaglutide [23].
While GLP-1 agonists may have therapeutic value for individuals at risk of life-threatening conditions, it is essential to draw a clear distinction between their appropriate medical use and their misuse by healthy individuals seeking to lose weight quickly.
The increasing popularity of these drugs raises concerns about society's unrealistic body image ideals and the potential risks associated with their use. Using semaglutide to manipulate body weight without medical supervision can have serious long-term effects on metabolic processes, even in healthy individuals.
Long-term
What happens after stopping semaglutide treatment? Weight regain occurs.
Wegovy openly acknowledges this on its website [19]. When the drug treatment is discontinued, hunger returns, potentially even stronger than before, leading to increased food intake and body fat accumulation. Clinical trials involving semaglutide typically span 1-2 years, so the long-term effects of prolonged use remain uncertain.
While the ideal duration of semaglutide treatment has yet to be determined, relying solely on a pharmaceutical product indefinitely is unlikely to be a sustainable approach for addressing excessive weight, as it diverts attention from addressing the underlying root causes of the issue.
Poor diet and lifestyle are the primary drivers of chronic diseases [20]. Medicalizing the treatment of these conditions promotes a quick-fix approach that fails to address the root cause of these issues. Utilizing semaglutide as a solution may enable patients to reach their desired weight loss targets without addressing the unhealthy dietary habits that initially contributed to their health issues.
This fundamental misunderstanding of the power of nutrition will lead to nutritional deficiencies, perpetuate the dependence on ultra-processed foods, and worsen the epidemic of insulin resistance, obesity, and other chronic diseases.
Widespread and improperly prescribed GLP-1 agonists without accompanying lifestyle interventions can be likened to applying a band-aid to a wound that needs stitches. To prevent and effectively manage chronic diseases, it is crucial to debunk weight loss myths and shift our focus towards evidence-based approaches, relying on scientific research rather than the allure of instant and effortless solutions. This should involve rediscovering the therapeutic potential of nutrition in clinical settings and as a public health initiative.
A different approach: lifestyle changes for lasting metabolic health
By embracing small yet impactful lifestyle modifications and using Veri's Four Pillars (nutrition, exercise, sleep, and stress) as a guide, we can change our brain chemistry and biology, leading to improved appetite regulation, blood sugar control, and sustainable weight management.
One of the key aspects of this approach is harnessing the therapeutic benefit of nutrition. Through strategic dietary choices, we can manipulate hunger-satiety hormones in our bodies.
For example, incorporating high-protein and healthy fat sources can enhance leptin sensitivity which plays a crucial role in regulating our appetite. Understanding how our dietary choices impact the signals sent to our metabolic system allows us to optimize the clearing of glucose from the bloodstream by boosting insulin sensitivity, without the need for medications that artificially increase insulin production. This, in turn, helps mitigate sugar spikes and crashes that often contribute to food cravings and other metabolic issues.
Nutrition is a powerful alternative to pharmaceutical interventions, such as GLP-1 agonists, for optimizing metabolic health and managing weight. Glucose monitoring and customizing dietary choices can address the root causes of metabolic imbalances and achieve long-lasting improvements in health.
Even for those on GLP-1 agonists for medical reasons, lifestyle improvements, like a healthy diet and exercise regimen, should be incorporated for maximum health outcomes and longevity. Importantly, for individuals managing diabetes or obesity, implementing dietary improvements can bring about significant results and enhance vitality and longevity.
While GLP-1 agonists are life-saving medications that improve the quality of life for many people, it’s crucial to acknowledge that nutrition and lifestyle interventions can offer powerful health benefits, without the associated risks.
Taking GLP-1s for medical reasons should not be shamed, but it shouldn't be relied on as an aesthetic quick-fix, either. Ultimately, we can't ignore the impact of nourishing food, exercise, quality sleep, and managing stress for living a long and healthy life. Embracing this type of balanced approach to a healthy lifestyle and using a continuous glucose monitor can help you tap into your body’s unique responses to foods and habits, allowing you to make informed lifestyle choices so you can achieve your health and weight goals, and maintain them for the long term.
Key takeaways
- The gut hormone GLP-1 regulates blood sugar levels and induces feelings of fullness after meals.
- GLP-1 agonist drugs, like semaglutide, mimic the effects of GLP-1 and are effective in managing severe blood sugar dysregulation and obesity.
- While GLP-1 agonists can have short-term side effects like nausea and upset stomach, continued use may lead to rapid muscle loss and compromise overall health and longevity.
- Over-reliance on GLP-1 agonist prescriptions neglects the importance of addressing the root causes of obesity and insulin resistance, which are primarily linked to poor diet and lifestyle choices.
- Emphasizing the power of nutrition and other lifestyle interventions, guided by Veri's Four Pillars, is essential for achieving better health, vitality, longevity, and freedom.
References:
- https://www.vanityfair.com/hollywood/2022/11/ozempic-hollywood-diet-drug
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235588/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119845/
- https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30179-7.pdf
- https://pubmed.ncbi.nlm.nih.gov/18640589/
- https://diabetesjournals.org/diabetes/article/63/2/407/34120/Give-the-Receptor-a-Brake-Slowing-Gastric-Emptying
- https://www.drugs.com/semaglutide.html
- https://www.uptodate.com/contents/glucagon-like-peptide-1-based-therapies-for-the-treatment-of-type-2-diabetes-mellitus
- https://www.ncbi.nlm.nih.gov/books/NBK572151/
- https://pubmed.ncbi.nlm.nih.gov/3514343/
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61335-0/fulltext
- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154206
- https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014
- https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(17)30074-9/fulltext
- https://www.medpagetoday.com/special-reports/features/102773
- https://www.singlecare.com/blog/ozempic-without-insurance/
- https://onlinelibrary.wiley.com/doi/full/10.1111/jdi.12900
- https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
- https://www.wegovy.com/about-wegovy/weight-loss-with-wegovy.html
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30041-8/fulltext
- https://pubmed.ncbi.nlm.nih.gov/24217090/
- https://jamanetwork.com/journals/jama/fullarticle/2810542
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529310/
