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Are GLP-1 Weight Loss Medications the New Hero's of Health?
Introducing Wegovy, the weight-loss wonder; Mounjaro, the metabolic marvel; and Saxenda, the shape-shifting solution. What are the benefits, drawbacks, and future of GLP-1 drugs in the fight against obesity and chronic diseases?
Dr Cam Rogers
June 03, 2025
Introduction
Nearly two-thirds of adults in England are overweight or obese1 :
In 2023-2024, 64.5% of adults aged 18 and older were classified as overweight or living with obesity. Obesity is increasing at an alarming rate and has been recognized as a significant contributor to reduced life expectancy and an increased burden of chronic diseases. As such, it is a complex public health concern on a global scale. The prevalence of overweight and obesity is particularly high among individuals living in the most deprived areas1 .
Weight loss strategies have included pharmacological options since the early 2000s, starting with Orlistat. This was the primary licensed weight loss medication in the UK until the introduction of GLP-1 medications. Orlistat has shown some success, with studies indicating that, on average, it leads to an additional weight loss of 2.5 to 5 kg over a period of 6 to 12 months compared to a placebo and lifestyle changes alone. However, gastrointestinal side effects can be troublesome, affecting up to 50% of users and often resulting in discontinuation of the medication. Additionally, the average weight loss is only modest when compared to newer treatments.
GLP-1 drugs were initially developed for diabetes treatment in the late 2000s, but their approval for weight management in the UK began with Saxenda (liraglutide), which became available in 2020 and received endorsement from the NHS. Wegovy (semaglutide) was approved by NICE for weight management in March 2023. Most recently, Mounjaro (tirzepatide) was licensed by the MHRA for weight loss and weight management in adults in November 2023.
What are GLP-1 Medications?
GLP-1, or Glucagon-like peptide-1, is a hormone composed of amino acids. It is primarily produced and secreted by specialized cells known as L-cells, which are located in the lining of the small intestine and colon. Smaller amounts of GLP-1 are also generated by specific neurons in the brainstem and, to a lesser extent, by cells in the pancreas.
This hormone is released into the bloodstream in response to food intake. It plays a crucial role in regulating blood sugar levels by stimulating insulin secretion and suppressing glucagon. Additionally, GLP-1 slows down stomach emptying and helps regulate appetite.
Understanding GLP-1's Actions - an analogy
Think of your body as a car, and eating a meal as filling up the gas tank. Your body needs to manage how much fuel (energy) it takes in and how quickly it burns it.
GLP-1 functions like a combination of an advanced fuel gauge and cruise control system. When you eat, it sends signals to your stomach to slow down how quickly it empties, helping you feel fuller for longer. It also communicates with your brain to let you know you’re satisfied, which encourages you to eat less. Additionally, GLP-1 assists your pancreas in releasing just the right amount of insulin, ensuring that your body handles the new fuel effectively without overwhelming the system.
Using the car analogy again, GLP-1 acts as a smart traffic controller for your blood sugar levels after meals. When you eat and your glucose levels rise, GLP-1 signals your body to boost insulin production, much like turning a traffic light to green. It also turns red to block the release of glucagon, a hormone that usually prompts the liver to release glucose into the bloodstream. This 'red light' function helps prevent a spike in blood sugar levels. Conversely, if blood glucose levels drop too low, GLP-1 switches to an orange light, signaling the release of glucagon to provide stored glucose—similar to a backup generator kicking in during a power outage.
In summary, GLP-1 delays stomach emptying, allowing insulin more time to regulate incoming sugar. It’s like a crossing guard slowing down traffic to prevent a bottleneck after a big meal.
Imagine GLP-1 medications turn up the volume in this car analogy system - they mimic the natural hormone, helping your body feel full sooner, keeping your appetite in check and manage blood sugar more smoothly. This is why individuals taking these drugs often find it easier to lose weight and maintain that weight loss. Their bodies become better at recognizing when they've had enough to eat and use energy more efficiently.
GLP-1 hormone acts as a traffic stop signal in glucose regulation and appetite control.
The Current Line-Up: GLP-1 Medications available in the UK
Most GLP-1 medications are injectable, meaning you inject a liquid medication with a needle and syringe.
Medication (Brand) & Active ingredient | Administration method | Frequency |
|---|---|---|
Wegovy - Semaglutide | Subcutaneous injection | Once weekly |
Saxenda - Liraglutide | Subcutaneous injection | Once daily |
Mounjaro - Tirzepatide | Subcutaneous injection | Once weekly |
There are other brands of Semaglutide that are available but for use in Type 2 diabetes rather than weight loss alone e.g. Ozempic, Rybelsus (a tablet version) but may be used off-label for weight loss in certain cases.
How to choose which agent to use?
Mounjaro, the metabolic marvel —> this generally results in the most weight loss (quoted as high as 22.5%). It is a once weekly injection which is felt to be more convenient. Uniquely compared to the other two, this acts at two receptors (GLP-1 and another one called GIP. GIP is another hormone that acts on GIP receptors sending a signal to help your pancreas release insulin to manage rising blood sugar levels). Tends to be better tolerated and has a lower discontinuation rate
Wegovy, the weight-loss wonder —> the second most efficacious with weight loss quoted at up to approximately 15%. Again this is a once weekly injection.
Finally, Saxenda, the shape-shifting solution —> this is a daily injection and has a lower efficacy quoted at approximately 6-10%.
Providers tailor the choice to individual needs, preferences and medical circumstances. They may also look at what has been tolerated previously and how much weight a person needs to loose.
The Heroic Side: Potential Benefits
In randomized clinical trials, GLP-1s have demonstrated significant efficacy in facilitating weight loss among individuals diagnosed with obesity or those classified as overweight, particularly when accompanied by weight-related health complications. These studies reveal a broad spectrum of placebo-adjusted weight reductions, ranging from 5% to as high as 18% of baseline body weight. This impressive range highlights the varying degrees of effectiveness, influenced by factors such as the specific GLP-1 agent used, dosage, treatment duration, and individual patient characteristics. These findings underscore the potential of GLP-1s as a valuable therapeutic option for weight management in populations facing obesity-related health challenges.
The licensed use for weight reduction are for those with obesity (BMI above 30kg/m2 ) or those who are overweight with weight-related co-morbidities (BMI >27kg/m2 - e.g. with cardiovascular disease).
Reducing cardiovascular events3
New data from a post-approval clinical study has demonstrated that Semaglutide branded as Wegovy, (administered as a 2.4 mg subcutaneous injection once a week for up to five years) lowers the incidence of major adverse cardiovascular events (MACE) compared to a placebo.
In a multinational, multicenter, placebo-controlled, double-blind trial that randomly assigned over 17,600 participants to receive either Wegovy or a placebo, Wegovy significantly reduced the risk of major adverse cardiovascular events by 20%4.
The Kryptonite: Risks, Side Effects and Limitations
The literature highlights several potential adverse drug reactions associated with these medications, as well as challenges to consider when using them. These concerns include gastrointestinal (GI) side effects, the risk of inadequate nutrient intake due to reduced food consumption compounded by insufficient nutritional counseling, and the potential loss of significant muscle mass and bone density. Additionally, there are high discontinuation rates, with approximately 50-67% of patients stopping treatment within one year and 85% by two years. This may be linked to side effects, costs, varying individual efficacy, or patient preferences. Furthermore, there is limited knowledge among the public and clinicians regarding the importance and implementation of complementary nutritional and lifestyle changes.
The table below summarizes the perceived challenges faced by both patients and prescribing clinicians.
Gastrointestinal side effects | Reports of dehydration due to nausea & vomiting. Abdominal pain (as high as 60% of patients) , diarrhoea and constipation reported More serious but less common risks of pancreatitis (1 in 100) and gall bladder disorders (1 in 10,000)5 | More likely at the start of treatment or after a dose increase, can settle with time. |
Fatigue Syndrome | A subgroup of patients who are very sensitive to rapid weight loss responding even at low doses of the drugs | 1 in 10 with rapid/ excessive weight loss - causing fatigue, listlessness, low energy for life, cognitive clouding. |
Loss of muscle mass | Data modeling indicates that muscle mass loss differs by sex, accounting for 10-15% of total weight reduction in females and 20-25% in males when structured strength training is not applied2 . | Resistance training is encouraged (with resistance bands or light weights), and eating an adequate protein intake to try and mitigate this impact |
Nutritional deficiencies due to reduced appetite and calorie reduction | Concerns of inadequate intake of minerals - calcium, iron, magnesium and zinc and for vitamins A, D, E, K, B1, B12 and C2 . | Symptoms of significant nutrient deficiency include excessive fatigue, hair loss, flaky or itchy skin, muscle weakness, slow wound healing, and unusual bruising. GI side effects may also contribute to malabsorption |
Loss of bone mass | Substantial weight reduction (≥14%) that occurs rapidly (within 3-4 months) is linked to significant bone loss2 . | The risks for postmenopausal women already at risk of losing bone mineral density must be considered. |
The Future: Are GLP-1’s Here to Stay?
I believe that GLP-1 medications have a promising future and are likely to remain a part of treatment approaches. However, there are important considerations to keep in mind when prescribing these medications. One crucial aspect is ensuring that patients have access to a lifestyle support program. This program should focus on the pillars and key principles of Lifestyle Medicine, enabling patients to make meaningful changes that promote ongoing weight loss, prevent relapse, and reduce the risks of bone and muscle loss, as well as nutritional deficiencies.
There are six principles of Lifestyle Medicine that patients starting a GLP-1 regimen should be supported to optimize2 .
Lifestyle Medicine Pillar | Suggestions to consider |
|---|---|
Nutrition | Careful baseline nutritional assessment. Personalized diets that are nutrient-dense and minimally processed. Prevention of micronutrient deficiencies. Ensuring adequate protein intake. |
Physical activity | Encouraging patient to meet the recommended 150 minutes of moderate intensity activity a week as well as regular strength and resistance training. |
Sleep | Poor sleep is linked to insulin resistance, increased hunger, and weight gain, which may negate some benefits of GLP-1s. Evaluate for co-morbidities associated with obesity, such as Obstructive Sleep Apnea. |
Avoidance of substances | Referral for cessation or counseling services where appropriate e.g. smoking/ alcohol services |
Social connections | Consider group medical visits, shared medical appointments, weight management, peer support groups, and addressing barriers to social engagement. |
Mental health and wellbeing | Mental stress management, with referral for cognitive-behavioral therapy or mindfulness-based stress reduction where appropriate |
Medication and The Microbiome
Lastly, my passion for the human microbiome compels me to examine the impact of GLP-1 hormones and medications on it
Natural interaction: Gut microbiome and GLP-1
A diverse and thriving microbiome produces important metabolites, including short-chain fatty acids (SCFAs) and secondary bile acids. These metabolites activate receptors on intestinal L-cells, stimulating the release of GLP-1.
There is also a reciprocal relationship with GLP-1 itself, which helps maintain a healthy microbiome by preserving gut barrier integrity, reducing inflammation, and preventing harmful microbial products from entering the bloodstream7 .
How GLP-1 Medications Influence the Microbiome
Studies suggest that GLP-1 medications can reshape the gut microbiome which may in turn contribute to their metabolic benefits.
There is data to suggest that they can:
Increase beneficial bacteria such as Akkermansia, Lactobacillus and Bifidobacterium
Reduce harmful bacteria such as Firmicutes (associated with obesity) and Enterobacteriaceae (pro-inflammatory)
Boost short chain fatty acid production - this in turn likely promotes further GLP-1 secretion
Modulate circadian rhythms
Reduce gut permeability, inflammation and therefore mitigate insulin resistance
Conclusion: Hero, Helper or Hype?
Obesity’s rising prevalence in the UK is a significant health and economic crisis, costing the NHS around £11.4 billion each year6 and affecting both quality of life and life expectancy. While GLP-1 medications offer real promise—helping many achieve significant weight loss and improved health—they are not a cure-all.
High rates of discontinuation, potential side effects, and the risk of nutritional deficiencies mean GLP-1s work best as part of a holistic, personalized lifestyle programme. For most people, these medications are a valuable helper rather than a hero—most effective when combined with long-term support for healthy habits and behaviour change.
Lasting success against obesity will always require more than a prescription; it needs informed, empowered individuals and a comprehensive approach to wellbeing.
Thanks for reading this far, I hope you enjoyed the article.
Over and out
Dr Cam
References
UK Government (2025, May 7). Obesity profile: short statistical commentary, May 2025. Retrieved from GOV.UK
Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional Priorities to Support GLP-1 Therapy for Obesity: A Joint Advisory From the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society. American Journal of Lifestyle Medicine. 2025;0(0). doi:10.1177/15598276251344827
MHRA approves GLP –1 receptor agonist semaglutide to reduce risk of serious heart problems in obese or overweight adults - GOV.UK. https://www.gov.uk/government/news/mhra-approves-glp-1-receptor-agonist-semaglutide-to-reduce-risk-of-serious-heart-problems-in-obese-or-overweight-adults.
A. Michael Lincoff, M.D. Kirstine Brown-Frandsen, M.D. et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med 2023;389:2221-2232
GLP-1 receptor agonists: reminder of the potential side effects and to be aware of the potential for misuse - GOV.UK. 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
Office for Life Sciences, Department of Health & Social Care, and Department for Science, Innovation and Technology. (2024). Obesity Healthcare Goals. Available at: https://www.gov.uk/government/publications/life-sciences-healthcare-goals/obesity-healthcare-goals
Zeng Y, Wu Y, Zhang Q, Xiao X. Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio. 2024 Jan 16;15(1):e0203223. doi: 10.1128/mbio.02032-23. Epub 2023 Dec 6. PMID: 38055342; PMCID: PMC10790698.
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