GLP-1 Medications: A Critical Examination of Emerging Weight Loss Treatments

By Steve Bennett, Dr Isabella Cooper, Professor Ben Bikman

Contents

• Executive Summary
• Introduction
• Understanding GLP-1: The Science Behind the Medication
• Critical Safety Concerns
• Muscle Wasting: Long-term Metabolic Consequences
• Nutritional Deficiency Crisis: Exacerbating Existing Problems
• Healthcare Sustainability and Economic Implications
• The Weight Regain Rebound
• Micro-Dosing: A More Precise Approach to GLP-1 Therapy
• Natural Alternatives and Evidence-Based Interventions
• Policy Recommendations for Parliamentary Action
• Conclusion
• References

Executive Summary

The emergence of GLP-1 receptor agonists as a weight loss intervention represents a pivotal moment in medical treatment, demanding a nuanced and comprehensive evaluation. History has witnessed numerous "wonder drugs" for weight loss—from amphetamines in the 1950s to fenfluramine-phentermine (fen-phen) in the 1990s, and most recently sibutramine—all of which were eventually discontinued due to severe adverse effects including heart valve damage, pulmonary hypertension, and cardiovascular complications.

Undoubtedly, being overweight or obese presents significant health and wellbeing challenges, and anything that can safely help people achieve better health should be pursued. However, with approximately 5% of the adult population now taking GLP-1 weight loss injections—a figure representing millions of individuals—are we potentially facing a future public health crisis reminiscent of past pharmaceutical disasters?

1. Nutritional Deficiency Risk: Learning difficulties, attention disorders, etc are often caused by nutrient deficiency
   
2. Individuals already struggling with malnutrition may face further nutritional compromise, potentially exacerbating existing health challenges.
3. Behavioural Modification Concerns: There is emerging evidence of a dangerous mindset emerging—a belief that pharmaceutical interventions can replace fundamental lifestyle and nutritional choices.
4. Metabolic Complexity: Significant muscle mass loss associated with these treatments raises profound questions about long-term metabolic health and weight management.
5. Comprehensive Side Effect Profile: A thorough examination of the potential adverse effects is crucial to understanding the true impact of these medications.
6. Micro Dosing: Standard high-dose protocols may be creating unnecessary problems, suggesting minimal effective dosing could control cravings, while avoiding severe side effects.
7. Natural Alternatives: Learning from past pharmaceutical failures while exploring evidence-based natural interventions that can support sustainable weight management.

This paper seeks to provide a balanced, evidence-based perspective that goes beyond the current narrative of GLP-1 medications as a simple weight loss solution. We must consider not just the immediate efficacy, but the broader implications for individual and public health, while acknowledging that time-tested natural approaches may offer safer, more sustainable alternatives.

Our goal is not to condemn, but to illuminate—to ensure that medical interventions serve the holistic well-being of individuals while we proceed with appropriate caution given the lessons of history.

GLP-1 receptor agonists, including semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro), represent a significant advancement in diabetes and obesity management. However, their rapid adoption and widespread use warrant careful parliamentary scrutiny. This comprehensive analysis examines the efficacy, safety profile, and broader implications of these medications for UK healthcare policy.

Introduction

GLP-1 receptor agonists have taken the medical world by storm as highly effective tools for managing type 2 diabetes and achieving significant weight loss. For many patients, these medications have been genuine game-changers, providing improved blood sugar control and meaningful progress toward weight loss goals. However, as these treatments transition from targeted medical interventions to widespread use, including through unregulated online channels, a comprehensive policy evaluation becomes essential.

What began as a targeted medical intervention has rapidly transformed into a widespread, largely unregulated phenomenon. Individuals are increasingly obtaining these medications through online channels, often without proper medical supervision or understanding of the potential long-term consequences. This trajectory presents concerning implications for public health, healthcare sustainability, and patient safety.

This analysis addresses four critical areas requiring parliamentary attention:

1. Public Health Safety: Emerging adverse effects and regulatory responses
2. Healthcare Sustainability: Cost-effectiveness and long-term outcomes
3. Patient Welfare: Nutritional and metabolic consequences
4. Healthcare Equity: Access and demographic impacts

Understanding GLP-1: The Science Behind the Medication

What is GLP-1?

To understand the implications of these medications, parliamentarians must first grasp the underlying science. GLP-1 (Glucagon-Like Peptide-1) is a naturally occurring hormone with a fascinating nomenclature history. When scientists first discovered GLP-1 in the 1980s, they named it based on its structural similarity to glucagon, despite performing nearly opposite functions. This "glucagon-like" designation reflects the scientific convention of naming newly discovered molecules based on their resemblance to known substances.

The historical context is important: GLP-1 and glucagon are both derived from the same precursor protein (proglucagon) and share approximately 50% amino acid sequence similarity. However, their effects are fundamentally different. While glucagon raises blood sugar by stimulating the liver to release stored glucose, GLP-1 lowers blood sugar by stimulating insulin release only when glucose levels are elevated.

Hormonal Function and Metabolic Impact

Hormones function as the body's internal messaging system, acting as invisible puppet masters that control virtually every aspect of metabolism. They are central to chronic illness development and are key to understanding obesity - not through calorie counting, but through hormonal management, particularly insulin and GLP-1.

GLP-1 is an incretin hormone secreted by the L cells of the small intestine in response to food intake. The term "incretin" derives from "intestinal secretion of insulin," highlighting its primary function. GLP-1 plays several critical roles in overall metabolic function:

1. Glucagon Suppression: GLP-1 inhibits glucagon secretion. Glucagon, insulin's metabolic opposite, increases blood glucose by directing the liver to break down stored glucose (glycogen). By suppressing glucagon, GLP-1 helps stabilise blood sugar levels and, when glycogen reserves are depleted, promotes the breakdown of stored body fat.
2. Gastric Emptying Delay: GLP-1 slows the rate at which food leaves the stomach, which prolongs feelings of fullness, reduces overall food intake, and increases satiety.
3. Central Nervous System Effects: GLP-1 activates satiety centres in the brain, directly acting on the hypothalamus to promote satiety, reduce hunger, and decrease the risk of overeating.
4. Vagal Nerve Activation: By activating vagal afferents, GLP-1 enhances the sense of fullness, helping individuals control their appetite more naturally.

The Medication Mechanism

Weight loss medications, regardless of brand name, are synthetic versions of the naturally occurring GLP-1 hormone. These synthetic replacements are designed to be more stable and longer-lasting than natural GLP-1, which is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4).

Critical Safety Concerns

The Mortality Data

The most alarming development in GLP-1 safety monitoring has been the revelation of significant mortality rates. Recent regulatory data reveals deeply concerning statistics that demand immediate parliamentary attention:

• 162 deaths have been reported to the FDA since 2018, with 94 associated with semaglutide (Ozempic and Wegovy) and 68 linked to tirzepatide (Mounjaro and Zepbound)
• 82 deaths have been reported to UK regulatory authorities prior to January 2025
• 40% increase in reported deaths over the last six months of the monitoring period
• FDA data shows over 62,000 reports of side effects, with approximately 10,000 classified as "serious," meaning patients were hospitalised or experienced life-threatening complications

Emergency Healthcare System Impact

One of the most dramatic findings emerged from a 2025 study published in the Annals of Internal Medicine, which estimated that nearly 24,499 emergency department visits in the United States were attributed to semaglutide medications between 2022 and 2023 [28]. 

This emergency department crisis has direct implications for the NHS, as similar patterns are likely emerging in the UK healthcare system. The strain on emergency services, combined with the need for specialised management of GLP-1-related complications, represents a hidden cost that must be factored into healthcare planning.

Legal Avalanche: Record-Breaking Litigation

The legal landscape surrounding GLP-1 drugs has exploded dramatically, with 1,809 lawsuits now pending against manufacturers as of May 2025 [29]. This represents a dramatic increase from earlier years, with cases involving severe complications including gastroparesis, thyroid tumours, pancreatitis, and bowel blockages.

The lawsuits have expanded to include vision loss claims following the publication of studies showing increased non-arteritic anterior ischemic optic neuropathy (NAION) risk. Law firms are now actively investigating cases where patients developed sudden blindness after taking these medications. This litigation explosion suggests significant patient harm and raises serious questions about informed consent protocols and regulatory oversight.

Comprehensive Adverse Effects Profile

The full spectrum of adverse effects associated with GLP-1 receptor agonists extends far beyond the commonly discussed gastrointestinal symptoms:

Psychiatric and Neurological Effects

A study published in 2024 but gaining significant attention in 2025 revealed that patients taking GLP-1 drugs showed a 195% higher risk of major depression, 108% increased risk for anxiety, and 106% elevated risk for suicidal behaviour [12]. The study, which analysed over 162,000 patients, found that GLP-1 treatment was associated with a 98% increased risk of any psychiatric disorders. Pharmacovigilance studies have identified significant associations with nervousness, stress, eating disorders, sleep disorders, binge eating, and self-induced vomiting [13].

These findings have led to urgent calls for prospective clinical trials to understand the full mental health implications of GLP-1 use. The most famous effect of these drugs is to reduce cravings for unhealthy foods, but this effect may be more widespread than initially appreciated, potentially reducing enjoyment of many life activities and explaining the substantially elevated risk of depression and other mental health problems.

Vision Loss Recognition

In a landmark decision that sent shockwaves through the medical community, the European Medicines Agency (EMA) officially declared NAION as a side effect of semaglutide medications in June 2025. This eye condition, often called an "eye stroke," can cause sudden, irreversible blindness in one eye. [1]

The EMA's conclusion was based on multiple epidemiological studies showing that adults with type 2 diabetes exposed to semaglutide had an approximately two-fold increased risk of developing NAION compared to those not taking the medication. The World Health Organization (WHO) immediately followed with an alert to healthcare professionals worldwide about this risk, marking the first time a major regulatory body has officially recognised this severe vision complication.

Additionally, GLP-1 drugs have been linked to several other potentially sight-threatening conditions, including an elevated risk of neovascular age-related macular degeneration (AMD), with people taking GLP-1 medications showing a risk of 0.2% compared to 0.1% in those not taking these drugs[2][3].

Dermatological Complications

A comprehensive 2025 systematic review revealed that GLP-1 drugs are associated with a broad spectrum of dermatologic effects, including serious immune-mediated conditions like bullous pemphigoid, pyoderma gangrenosum, and generalised exanthematous pustulosis [27]. The review found that 34 out of 51 studies reported adverse skin effects, including severe hypersensitivity reactions.

Gastrointestinal Complications

Studies have found that people taking GLP-1 drugs were 66% more likely [6] to be diagnosed with gastroparesis (stomach paralysis) compared to those not taking these medications. This condition involves delayed gastric emptying and can cause severe nausea, vomiting, and digestive complications that may persist even after discontinuation [7].

In a drug safety update, published in October 2024, the MHRA reported that it had received 7,228 reports of common gastrointestinal reactions associated with GLP-1indicated for weight management.

Gallbladder and Biliary Disease

Meta-analyses demonstrate that GLP-1 receptor agonists are associated with increased risks of gallbladder diseases, including cholelithiasis (gallstones), cholecystitis (gallbladder inflammation), and biliary disease [8] [9] [10]. The risk appears to be dose-dependent and higher in weight-loss trials compared to diabetes trials [11].

Pancreatitis and Pancreatic Concerns

The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has reported 10 deaths linked to pancreatitis associated with GLP-1 medications. Case reports describe patients developing pancreatitis within months of starting treatment, with symptoms including progressive abdominal pain, vomiting, and elevated pancreatic enzymes.

The MHRA has launched a study to investigate whether pancreatitis [5] risk may be influenced by genetic makeup, calling for patients to report side effects through a specialised biobank project. This genetic component raises questions about patient screening protocols and personalised medicine approaches. The UK Government also have concerns about pancreatitis and have published on their website [4].

Cardiovascular Effects

While GLP-1 medications are generally considered cardiovascular protective, they consistently increase heart rate, with studies showing increases of 2.5-3.5 beats per minute [20] [21] [22]. However, while some concerns existed about arrhythmia risk, comprehensive analyses suggest GLP-1 drugs do not significantly increase the risk of various arrhythmias [23].

Thyroid Cancer Risk

Studies have documented increased thyroid cancer risk, particularly medullary thyroid cancer, with GLP-1 receptor agonist use. Research shows cumulative use from 1-3 years was associated with a 58% increased risk of all thyroid cancers and a 78% increased risk of medullary thyroid cancer specifically [14] [15]. The FDA has issued warnings against use in individuals with family or personal history of medullary thyroid cancer [16].

Hair Loss

Clinical trials have documented hair loss as a side effect, with 3% of adults using Wegovy reporting alopecia compared to 1% using placebo [19]. Although, this is thought to be related to telogen effluvium caused by rapid weight loss rather than a direct drug effect.

Particularly concerning is the hair loss epidemic, with a groundbreaking study in 2025 specifically linking semaglutide to a higher risk of hair loss, especially in women. The American Hair Loss Association has issued strong warnings about the potential for these medications to trigger not only temporary hair loss but also early onset male and female pattern hair loss, which can result in permanent baldness.

Anaphylaxis and Hypersensitivity

GLP-1 receptor agonists are associated with a modestly increased risk of anaphylactic reactions compared to other diabetes medications, with hazard ratios ranging from 1.15 to 1.38 depending on the comparison drug [24] [25].

Dehydration and Electrolyte Imbalances

The gastrointestinal side effects of GLP-1 medications, combined with reduced appetite and thirst, can lead to significant dehydration and electrolyte imbalance [26]. This can exacerbate other side effects and requires careful monitoring and management. 

Muscle Wasting: Long-term Metabolic Consequences

Alarming Body Composition Changes

One of the most concerning and underreported aspects of GLP-1 therapy is the significant loss of lean body mass. Research has revealed that 15-40% of total weight loss achieved through GLP-1 receptor agonists comes from fat-free mass, including muscle and water, rather than fat tissue [17][18].

This rapid muscle mass decline places certain populations at higher risk for sarcopenia and associated complications, particularly older adults and those with chronic conditions [17].

Metabolic Consequences of Muscle Loss

The implications of this muscle wasting extend far beyond aesthetics:

1. Metabolic Rate Reduction: Muscle tissue burns significantly more energy than fat tissue. Once patients stop taking GLP-1 medications, their reduced muscle mass results in a slower metabolism, leading to accelerated weight regain.
2. Sarcopenia Risk: Recent studies have warned that the rapid and significant decline in muscle mass places patients already predisposed to sarcopenia at higher risk for accelerated muscle loss and adverse events.
3. Unfavourable Body Composition: When weight is regained after discontinuation, it is often primarily fat rather than muscle, leading to an unfavourable shift in body composition and compromised metabolic health.
4. Functional Decline: Muscle loss can impact physical function, mobility, and quality of life, particularly in older adults.
   

Long-term Implications for Healthcare Systems

The muscle wasting associated with GLP-1 therapy presents long-term challenges for healthcare systems:

• Increased risk of falls and fractures in older adults
• Potential need for additional interventions to preserve muscle mass
• Long-term metabolic complications that may require ongoing management
• Increased healthcare utilisation for sarcopenia-related complications

Nutritional Deficiency Crisis: Exacerbating Existing Problems

The Malnutrition Paradox

Most individuals in the modern world are overfed yet undernourished. Very few people meet the recommended daily consumption of fibre, protein, vitamins, and minerals. Those who are overweight or obese tend to already be the most nutritionally deficient populations.

When GLP-1 medications reduce food intake but the composition of the diet remains unchanged, patients become even more nutritionally deficient. This creates a dangerous cycle where individuals consuming fewer calories of already poor-quality food experience:

• Inadequate protein intake leading to muscle wasting
• Vitamin and mineral deficiencies affecting immune function
• Reduced fibre consumption impacting gut health
• Decreased intake of essential fatty acids
• Compromised micronutrient status affecting metabolic function

Behavioural Modification Concerns

There is emerging evidence of a dangerous mindset developing among GLP-1 users - a belief that pharmaceutical interventions can replace fundamental lifestyle and nutritional choices. This psychological dependence on medication rather than addressing root causes creates several problems:

1. Delayed Lifestyle Changes: Patients may postpone necessary dietary and lifestyle modifications, believing the medication alone is sufficient.
2. Reduced Self-Efficacy: Reliance on external pharmaceutical solutions may diminish patients' confidence in their ability to manage their health through lifestyle approaches.
3. Missed Educational Opportunities: The period of medication use represents a critical window for learning sustainable habits, but this opportunity is often missed when patients focus solely on pharmaceutical solutions.
4. Unrealistic Expectations: Patients may develop unrealistic expectations about weight management, leading to disappointment and potential psychological harm when medications are discontinued.
5. Neglect of Underlying Causes: The focus on pharmaceutical solutions may divert attention from addressing underlying metabolic dysfunction, food relationships, and lifestyle factors that contribute to obesity.

Healthcare Sustainability and Economic Implications

Discontinuation Rates and Treatment Failure

Real-world data paints a concerning picture of treatment sustainability:

• 50% of patients discontinue GLP-1 receptor agonists within one year of initiating treatment
• 70% discontinuation rate by year two
• These high dropout rates significantly impact cost-effectiveness calculations and clinical outcomes
  

The reasons for discontinuation are multifaceted:

• Cost and Accessibility: GLP-1 medications can be prohibitively expensive, and insurance coverage is not always comprehensive, leading many patients to discontinue treatment due to financial constraints.
• Perceived Lack of Progress: Over time, some individuals feel that the benefits—such as weight loss or improved blood sugar control—plateau, which can discourage continued use.
• Lifestyle Factors: Long-term adherence often requires pairing the medication with significant lifestyle changes, such as dietary adjustments and increased physical activity, which not all patients are prepared to maintain.
• Side Effects: Gastrointestinal complications, including nausea and vomiting, become so unbearable that many patients conclude the benefits aren't worth the discomfort.
• Return of Cravings: Initial reduction in sweet cravings may return to normal levels by two years of treatment, diminishing the medication's effectiveness and patient motivation.

NHS Financial Implications

The economic implications for the NHS are substantial:

• Direct Costs: The high cost of GLP-1 medications represents a significant budget burden, particularly given the need for long-term or potentially lifelong treatment. Current UK pricing for these medications ranges from £150-300 per month per patient, with annual costs exceeding £1,800 - £3,600 per individual. When scaled across the eligible population - potentially millions of UK adults with obesity or diabetes - the total NHS expenditure could reach billions of pounds annually. This represents one of the largest single pharmaceutical budget impacts in NHS history, comparable to the introduction of hepatitis C treatments or cancer immunotherapies.
• Hidden Costs: Emergency department visits, management of adverse effects, and treatment of complications add substantial hidden costs to the healthcare system.
• Opportunity Costs: Resources devoted to GLP-1 prescriptions could potentially be allocated to preventive interventions or lifestyle medicine programmes with longer-lasting benefits.
• Sustainability Questions: The combination of high costs, high discontinuation rates, and rapid weight regain raises fundamental questions about the long-term sustainability of widespread GLP-1 use.

 
The Weight Regain Rebound

Research from the University of Oxford delivered devastating news for long-term weight management expectations. The study found that patients typically regain their original weight within an average of 10 months after stopping GLP-1 medications.

Specifically, those using higher-dose medications like Wegovy and Mounjaro lost an average of 16kg but regained 9.6kg in the first year after discontinuation, suggesting they could expect to regain all lost weight within approximately 20 months. This finding raises serious questions about the sustainability and cost-effectiveness of these treatments.

The Metabolic Damage Behind the Rebound

What makes this weight regain particularly concerning is the body composition changes that occur during the process. As Dr. Benjamin Bikman notes, when patients lose weight on GLP-1 drugs, up to 40% of that weight loss comes from precious lean mass - muscle, bone, and connective tissue. However, when weight returns after discontinuation, it predominantly comes back as fat tissue.

This creates a devastating metabolic scenario: patients may end up at a similar weight to where they started, but with a higher percentage of body fat and lower muscle mass. The result is a slower metabolism, reduced insulin sensitivity, and a body that is metabolically worse off than before treatment began.

Multiple studies have documented this "yo-yo" effect, where each cycle of weight loss and regain leaves patients more metabolically compromised. The financial cost of repeated treatment cycles, combined with the progressive metabolic damage, raises fundamental questions about whether current high-dose protocols are doing more harm than good in the long term.

Micro-Dosing: A More Precise Approach to GLP-1 Therapy

I am going to hand this section on Micro Dosing over to Dr. Benjamin Bikman, a leading biomedical scientist and professor of Cell Biology at Brigham Young University whose groundbreaking research on metabolic disorders and insulin resistance has positioned him at the forefront of understanding how modern diseases develop. Dr Bikman offers a perspective on GLP-1 drugs that challenges the current medical paradigm and demands serious consideration from both healthcare providers and patients alike.

“What if we've been thinking about GLP-1 drugs all wrong? What if the standard dosing protocols are like using a sledgehammer when we need a scalpel? This brings me to what I consider a revolutionary approach: micro-dosing.

When I look at the typical prescribing patterns for semaglutide, we're talking about 2.4 milligrams as the target dose for weight loss. But here's what fascinates me from a physiological standpoint - we're not trying to replicate the natural hormone, we're obliterating it. We're creating pharmacological levels that are so far beyond what the body would naturally produce that we shouldn't be surprised when we see these dramatic side effects.

Think about it this way: if someone has that blunted GLP-1 response to carbohydrates that I mentioned earlier - and remember, this is the core problem in obesity - do we really need to hit them with a metabolic sledgehammer? Or can we be more surgical in our approach?

What I've been advocating for, is that we can achieve the primary benefit we're after - breaking the carbohydrate craving cycle - with a fraction of the dose. Maybe we're talking about 0.25 milligrams instead of 2.4. Maybe even less. The goal isn't to eliminate hunger entirely, which frankly borders on pathological. The goal is to restore that natural satiety signal that gets triggered when we eat carbohydrates.

From a mechanistic standpoint, this makes perfect sense. We're not trying to pharmacologically paralyse the digestive system or create an artificial state of perpetual fullness. We're trying to nudge the system back toward normal function. We're trying to restore what obesity took away - that natural ability to feel satisfied after eating carbohydrates.

This micro-dosing approach could potentially sidestep many of the issues we've discussed. Lower doses mean less risk of gastroparesis, potentially less impact on mood and mental health, and certainly less muscle wasting. But most importantly, it means we're working with the body's natural systems rather than overwhelming them.

The beauty of this approach is that it's not about creating pharmaceutical dependency. It's about using the minimum effective dose to retrain the metabolic system, then cycling off to see if those natural mechanisms can sustain themselves. It's precision medicine at its finest - using just enough intervention to restore normal function without creating new problems.

Of course, this requires a fundamental shift in how we think about these medications. Instead of viewing them as long-term weight loss solutions, we're using them as metabolic re-education tools. Instead of maximising weight loss at any cost, we're specifically targeting the carbohydrate craving pathway that's been disrupted by obesity.

This is where the future of GLP-1 therapy needs to go - not bigger doses and longer durations, but smarter, more targeted approaches that respect the body's natural wisdom while addressing the specific metabolic dysfunction that got us into trouble in the first place.”

Natural Alternatives and Evidence-Based Interventions

The human body's remarkable ability to adapt presents a significant challenge with GLP-1 drugs that highlights the critical need for natural alternatives. A 2022 trial published in Nature Medicine, known as the STEP 5 study [39], revealed a troubling pattern: after two years of continuous use, hunger and sweet cravings returned to pre-drug levels even while participants remained on the medication. This fading effectiveness, or diminishing returns, suggests that relying solely on synthetic GLP-1 receptor agonists may not provide the sustainable, long-term solution that patients need for lasting metabolic health. As the initial benefits inevitably wane over time, it becomes increasingly clear that we must address this limitation by exploring and implementing natural strategies that can work synergistically with the body's own mechanisms, rather than against them, to maintain the metabolic improvements that these drugs initially provide.

Dietary Approaches to Natural GLP-1 Enhancement

Research has identified several natural approaches to enhancing GLP-1 levels that may provide sustainable alternatives or complementary strategies:

Low-Carbohydrate Dietary Interventions

As far back as 1996, research showed how postprandial (after a meal) GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects [38].

Studies have demonstrated that low-carbohydrate meals can significantly enhance natural GLP-1 production. In a 2024 study, participants consuming a low-carbohydrate meal showed significantly higher postprandial GLP-1 levels compared to those consuming a low-fat meal. Specifically, the active GLP-1 concentrations after the low-carbohydrate meal were more than double those following the low-fat meal [30].

This research highlights the potential for low-carbohydrate dietary strategies to naturally enhance GLP-1 levels, thereby supporting metabolic health and appetite regulation without pharmaceutical intervention. The implications are significant: by focusing on nutrient-dense, lower-carbohydrate foods such as leafy greens, non-starchy vegetables, healthy fats, and high-quality proteins, individuals may achieve similar metabolic benefits to those provided by medications.

The KetoSAge study ran by Dr Isabella Cooper at the Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, found that when women followed a low-carbohydrate diet and stayed in nutritional ketosis, their levels of GLP-1were significantly higher than when they ate more carbohydrates. At the same time, their insulin levels, insulin resistance, and leptin (a hormone linked to hunger and fat storage) were all lower, showing a healthier overall metabolic state. These benefits happened without any medications, suggesting that simply eating in a way that supports ketosis significantly elevates GLP-1 naturally and improves health. When ketosis was interrupted by eating more carbohydrates, GLP-1 levels significantly dropped, and signs of poorer metabolic health returned. This shows that a low-carb lifestyle is an effective way to support healthy hormones, appetite control, and long-term wellness [37]. 

Research reveals a significant difference in GLP-1 secretion between obese and lean individuals in response to carbohydrate intake. Specifically, obese individuals exhibited a suppressed GLP-1 response compared to lean individuals after consuming carbohydrates, with lean individuals showing a 3-4 times higher response [31]. This suggests that people struggling with obesity may have a reduced satiety signal, making it harder to feel full after eating, and highlighting the importance of dietary interventions that can restore normal GLP-1 function.

Fibre: The Foundation of GLP-1 Stimulation

Research indicates that dietary fibre intake, particularly fermentable fibre, can positively influence the release of GLP-1 (glucagon-like peptide-1), a gut hormone known for its role in regulating appetite, blood sugar, and potentially aiding in weight management [32]. Studies suggest that fibre, especially when fermented in the colon, can increase GLP-1 synthesis and secretion by influencing L-cells in the intestine.

Dietary fibre plays a pivotal role in enhancing GLP-1 activity through its fermentation by gut bacteria. This fermentation process produces short-chain fatty acids (SCFAs), which directly stimulate GLP-1 secretion from intestinal L-cells. Fibre also:

• Slows gastric emptying, ensuring a more gradual release of glucose into the bloodstream
• Reduces the likelihood of insulin spikes
• Supports a healthy gut microbiome, which is increasingly recognised as a critical regulator of GLP-1 production and overall metabolic health
• Promotes appetite suppression through multiple mechanisms
  

Yerba Mate: A Natural GLP-1 Enhanced

Yerba mate, a traditional South American herbal tea, has demonstrated remarkable effects on GLP-1 stimulation. Research by Professor Ben Bikman at Brigham Young University found that yerba mate significantly increases GLP-1 by 40-50%, likely due to its ferulic acid content and activation of bitter taste receptors that also reduce sweet cravings [33].

The mechanisms by which yerba mate enhances GLP-1 function include:

• Stimulating GLP-1 Production: Yerba mate contains bioactive molecules, such as chlorogenic acids and saponins, which directly activate intestinal L-cells to produce more GLP-1. Chlorogenic acids specifically enhance the responsiveness of L-cells to food stimuli, effectively boosting natural GLP-1 secretion after meals.
• Prolonging GLP-1 Action: Yerba mate's high ferulic acid content inhibits dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for breaking down GLP-1. By reducing DPP-4 activity, ferulic acid allows GLP-1 to remain active in the bloodstream for longer durations, amplifying its effects on satiety and blood sugar regulation.
• Reducing Inflammation: Chronic inflammation can impair GLP-1 signalling and insulin sensitivity. Yerba mate's rich antioxidant profile—including polyphenols—helps reduce oxidative stress and inflammation, creating a more favourable environment for GLP-1 activity.
• Enhancing Metabolic Function: Beyond GLP-1 effects, yerba mate provides sustained energy without the crashes associated with other stimulants, making it an ideal complement to metabolic health interventions.

Collagen Peptides and Protein Optimisation

Emerging research reveals that collagen peptides offer a promising natural approach to supporting GLP-1 function while simultaneously addressing one of the most concerning side effects of pharmaceutical GLP-1 treatments—significant muscle loss. This dual-action mechanism positions collagen supplementation as a potentially valuable component of a comprehensive metabolic health strategy. [34].

Studies have demonstrated that collagen peptides can significantly increase endogenous GLP-1 secretion while improving blood glucose metabolism and insulin sensitivity. The mechanism appears to involve specific amino acid sequences within collagen peptides that stimulate intestinal L-cells to produce more GLP-1 naturally. This stimulation occurs through the same pathways that dietary proteins normally activate, but collagen peptides appear to be particularly effective due to their unique amino acid profile, particularly high concentrations of glycine, proline, and hydroxyproline.

Research has shown that collagen peptide supplementation can increase postprandial (after-meal) GLP-1 levels by 20-30% compared to control groups, while simultaneously improving glucose tolerance and reducing insulin resistance markers. This natural enhancement of GLP-1 production offers several advantages over pharmaceutical interventions, including better tolerability and the absence of the severe gastrointestinal side effects commonly associated with GLP-1 receptor agonists [35].

The combination of enhanced GLP-1 production and muscle preservation creates a synergistic effect that addresses multiple metabolic pathways simultaneously.

Sleep and Lifestyle Factors

The Sleep-GLP-1 Connection - Impaired GLP-1 Responses to Food
Sleep deprivation significantly blunts GLP-1 production and response. Individuals sleeping less than 6 hours per night exhibit 15-25% lower postprandial GLP-1 responses compared to those achieving 7-9 hours of quality sleep [36]. 

This occurs through:

• Reduced L-cell sensitivity: Sleep deprivation decreases intestinal L-cell responsiveness to nutrients
• Altered circadian rhythm: Sleep disruption desynchronises GLP-1 production patterns with meal timing
• Inflammatory interference: Poor sleep increases inflammatory markers that interfere with GLP-1 function
  

Quality sleep plays a crucial role in GLP-1 function:

• Poor sleep impairs GLP-1 responses to food
• Sleep deprivation reduces satiety signals
• Inadequate rest can create a cycle of increased hunger and poor sleep quality
• Addressing sleep hygiene may enhance natural GLP-1 effectiveness

Policy Recommendations for Parliamentary Action

Immediate Regulatory Actions Required

Enhanced Safety Monitoring and Reporting Systems

• Remove the Eatwell guideline, as it is at the core of muting GLP-1
• Establish a comprehensive national adverse event tracking system specifically for GLP-1 medications
• Review and update current prescribing guidelines to reflect emerging safety data
• Establish mandatory waiting periods and counselling requirements before initiation
• Create specialised training requirements for healthcare providers prescribing GLP-1 medications
• Implement strict controls on online sales and distribution of GLP-1 medications
• Create public awareness campaigns about the risks of unregulated procurement
• Develop standardised patient education materials
• Establish protocols for monitoring and addressing nutritional deficiencies
  

Healthcare Professional Education 

• Mandate continuing education on GLP-1 safety and management
• Provide training on natural GLP-1 enhancement strategies
  

Public Awareness and Education 

• Launch public health campaigns about GLP-1 risks and benefits
• Educate the public about natural alternatives and lifestyle approaches
• Provide resources for patients considering GLP-1 treatment
• Create support networks for patients transitioning off medications

Further Recommendations:

• Establish specialised GLP-1 clinics with multidisciplinary teams
• Implement mandatory nutritional counselling and monitoring
• Establish mandatory lifestyle intervention programmes alongside GLP-1 treatment
• Develop protocols for transitioning patients first to micro dosing, then to natural GLP-1 enhancement strategies
• Fund research into combined pharmaceutical and lifestyle interventions
• Develop school-based nutrition and lifestyle education programmes
• Create community-based interventions targeting high-risk populations

Conclusion: A Path Forward for Sustainable Healthcare

The emergence of GLP-1 receptor agonists represents both a significant medical advancement and a complex policy challenge. While these medications offer substantial benefits for certain patients, the mounting evidence of serious adverse effects, high discontinuation rates, and sustainability concerns demands immediate parliamentary attention and action.

The UK stands at a critical juncture. The decisions made today regarding GLP-1 policy will have profound implications for public health, healthcare sustainability, and patient safety for decades to come. The evidence presented in this analysis suggests that a balanced approach is essential—one that recognises the therapeutic value of GLP-1 medications while addressing their significant limitations and risks.

The Opportunity for Leadership

The UK has a unique opportunity to lead globally in developing comprehensive, sustainable approaches to obesity management. This leadership can manifest through:

• Pioneering integrated care models that combine the best of pharmaceutical and lifestyle interventions
• Investing in prevention strategies that address the root causes of obesity
• Developing innovative research programmes that advance our understanding of metabolic health
• Creating regulatory frameworks that prioritise patient safety while supporting medical innovation
  

A Call for Balanced Action

This analysis does not advocate for the wholesale rejection of GLP-1 medications, nor does it suggest that they represent a panacea for obesity. Instead, it calls for a thoughtful, evidence-based approach that:

• Prioritises patient safety through enhanced monitoring and regulation
• Integrates pharmaceutical and lifestyle interventions for optimal outcomes
• Invests in sustainable, long-term solutions to the obesity epidemic
• Ensures equitable access to comprehensive care
• Supports ongoing research into both pharmaceutical and natural approaches
  

The stakes are high. The decisions made by Parliament regarding GLP-1 policy will affect millions of patients, the sustainability of the NHS, and the UK's leadership in global health policy. The evidence demands action, and the time for that action is now.

By taking decisive steps to address the challenges outlined in this analysis while supporting the continued development of safe and effective treatments, Parliament can ensure that medical innovations truly serve the public interest while maintaining the highest standards of patient safety and healthcare sustainability.

___________________

This analysis is based on peer-reviewed research and regulatory data current as of 2025. Continued monitoring and evaluation of emerging evidence is essential for informed policy development.

[1] https://www.webmd.com/obesity/news/20250212/glp-1-drugs-again-linked-blindness-risk - GLP-1 Drugs Again Linked to Blindness Risk

[2] https://jamanetwork.com/journals/jamaophthalmology - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration

[3] Medical News Today - Review links 3 potentially-blinding eye conditions to GLP-1 drugs like Ozempic

[4] https://www.gov.uk/drug-safety-update/glp-1-receptor-agonists-reminder-of-the-potential-side-effects-and-to-be-aware-of-the-potential-for-misuse

[5] https://pmc.ncbi.nlm.nih.gov/articles/PMC5808258/ - Acute pancreatitis during GLP-1 receptor agonist treatment. A case report

[6] https://eposters.ddw.org Digestive Disease Week - INCIDENCE OF GASTROINTESTINAL SIDE EFFECTS IN PATIENTS PRESCRIBED GLUCAGON-LIKE PEPTIDE-1 (GLP-1) ANALOGS: REAL-WORLD EVIDENCE

[7] https://www.medicalnewstoday.com/articles/using-drugs-like-ozempic-for-weight-loss-may-lead-to-stomach-paralysis-pancreatitis - Using drugs like Ozempic for weight loss may lead to stomach paralysis, pancreatitis

[8] https://pmc.ncbi.nlm.nih.gov/articles/PMC8961394/ - Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases

[9] - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790392 - Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases

[10] - https://pubmed.ncbi.nlm.nih.gov/35344001/ - Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials

[11] - https://pubmed.ncbi.nlm.nih.gov/35344001/ - Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials

[12] https://www.nature.com/articles/s41598-024-75965-2 - The risk of depression, anxiety, and suicidal behaviour in patients with obesity on glucagon like peptide-1 receptor agonist therapy

[13] - https://pmc.ncbi.nlm.nih.gov/articles/PMC10882716/ - Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database

[14] - https://pmc.ncbi.nlm.nih.gov/articles/PMC10563602/ - Glucagon-like peptide 1 receptor agonists and thyroid cancer: is it the time to be concerned?

[15] - https://diabetesjournals.org/care/article/46/2/384/147888/GLP-1-Receptor-Agonists-and-the-Risk-of-Thyroid 

[16] - https://www.news-medical.net/news/20250128/GLP-1RA-initiation-linked-to-new-thyroid-cancer-diagnoses.aspx

[17] - https://pubmed.ncbi.nlm.nih.gov/40289060/ - Impact of GLP- 1 Receptor Agonist Therapy in Patients High Risk for Sarcopenia. DOI: 10.1007/s13668-025-00649-w

[18] https://www.healthline.com/health-news/ozempic-muscle-mass-loss - Ozempic Can Cause Major Loss of Muscle Mass and Reduce Bone Density

[19] - https://www.drugs.com/medical-answers/ozempic-wegovy-mounjaro-cause-hair-loss-3575019/ - Can Ozempic, Wegovy, Mounjaro or Zepbound cause hair loss?

[20] https://pmc.ncbi.nlm.nih.gov/articles/PMC9403613/ - Effects of GLP-1 receptor agonists on arrhythmias and its subtypes in patients with type 2 diabetes: A systematic review and meta-analysis

[21]- https://academic.oup.com/cardiovascres/article/120/12/1427/7687589 https://doi.org/10.1093/cvr/cvae120 - Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node

[22] - https://pmc.ncbi.nlm.nih.gov/articles/PMC11404059/ - Glucagon-like Receptor-1 agonists for obesity: Weight loss outcomes, tolerability, side effects, and risks

[23] - https://pmc.ncbi.nlm.nih.gov/articles/PMC9403613/ - Effects of GLP-1 receptor agonists on arrhythmias and its subtypes in patients with type 2 diabetes: A systematic review and meta-analysis

[24] - https://pmc.ncbi.nlm.nih.gov/articles/PMC9989345/ - Glucagon-Like Peptide 1 Receptor Agonists and Risk of Anaphylactic Reaction Among Patients With Type 2 Diabetes: A Multisite Population-Based Cohort Study

[25] - https://pmc.ncbi.nlm.nih.gov/articles/PMC10973896/ - Risk of Anaphylaxis Among New Users of GLP-1 Receptor Agonists: A Cohort Study

[26] - https://dripdrop.com/blogs/hydration-blog/why-hydration-is-crucial-on-glp-1-medications-tips-benefits - Why Hydration is Crucial on GLP-1 Medications

[27] - https://pmc.ncbi.nlm.nih.gov/articles/PMC12110338/ - A Closer Look at the Dermatological Profile of GLP-1 Agonists

[28] - https://www.acpjournals.org/doi/10.7326/ANNALS-24-03258 - U.S. Emergency Department Visits Attributed by Clinicians to Semaglutide Adverse Events, 2022–2023

[29] https://federal-lawyer.com/injury-lawsuit/ozempic/#:~:text=May%202%2C%202025%20%E2%80%93%20There%20were,involved%20gastrointestinal%20issues%2C%20including%20gastroparesis. - Ozempic Lawsuit (July Update)

[30] https://pmc.ncbi.nlm.nih.gov/articles/PMC8278161/#:~:text=Postprandial%20plasma%20active%20GLP%2D1,Table%20S3%20of%20Supplementary.
doi: 10.1017/jns.2021.41- Postprandial effects of a whey protein-based multi-ingredient nutritional drink compared with a normal breakfast on glucose, insulin, and active GLP-1 response among type 2 diabetic subjects: a crossover randomised controlled trial

[31] https://gut.bmj.com/content/38/6/916 - Attenuated GLP-1 secretion in obesity: cause or consequence?

[32] https://pmc.ncbi.nlm.nih.gov/articles/PMC5148911 - Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review

[33] https://www.researchgate.net/publication/388944561 - The Incretin Effect of Yerba Maté (Ilex paraguariensis) Is Partially Dependent on Gut-Mediated Metabolism of Ferulic Acid

[34] - https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.4538 - A Specific Collagen Hydrolysate Improves Postprandial Glucose Tolerance in Normoglycemic and Prediabetic Mice and in a First Proof of Concept Study in Healthy, Normoglycemic and Prediabetic Humans

[35] - https://pmc.ncbi.nlm.nih.gov/articles/PMC11606891 - A Specific Collagen Hydrolysate Improves Postprandial Glucose Tolerance in Normoglycemic and Prediabetic Mice and in a First Proof of Concept Study in Healthy, Normoglycemic and Prediabetic Humans

[36] - https://pubmed.ncbi.nlm.nih.gov/26530153 - Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers

[37] - https://doi.org/10.3390/biomedicines12071553 - Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females

[38] https://pubmed.ncbi.nlm.nih.gov/8984033/ - Attenuated GLP-1 secretion in obesity: cause or consequence?

[39] https://www.nature.com/articles/s41591-022-02026-4 - Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial