Mounjaro Outperforms Wegovy in Major Weight-Loss Drug Trial

The World Health Organization (WHO) has issued its first global guideline on the use of glucagon‑like peptide‑1 (GLP‑1) medicines to treat obesity as a chronic, relapsing disease in adults (World Health Organization [WHO], 2025a). The guidance offers conditional recommendations rather than prescriptive rules and stresses that medicines alone will not reverse the obesity epidemic; person‑centred, lifelong care remains fundamental. Ongoing concerns include limited long‑term safety data, high treatment costs, constrained supply and the real risk that access to GLP‑1 medicines could widen existing health inequalities if policy makers do not act deliberately to protect equity (WHO, 2025a, 2025b).

The global burden of obesity

Obesity is now recognised as a complex, chronic disease and a major driver of non‑communicable conditions such as cardiovascular disease, type 2 diabetes and several cancers (GBD Obesity Collaborators, 2024). It also worsens outcomes when people develop infectious diseases, as seen clearly during the COVID‑19 pandemic (Popkin et al., 2020). WHO estimates that more than one billion people worldwide are living with obesity and warns that, without effective action, this figure could roughly double by 2030, contributing to millions of avoidable deaths each year (WHO, 2022, 2025a).

The economic impact is substantial. Global costs linked to obesity and overweight, driven by increased healthcare use, disability and loss of productivity, are projected to reach around 3 trillion US dollars a year by 2030 (World Obesity Federation, 2023). By providing clearer guidance on when and how to use GLP‑1 medicines within comprehensive obesity care, WHO aims to help countries improve outcomes while using resources more wisely (WHO, 2025a).

A policy milestone: conditional recommendations

The new guideline follows WHO’s earlier decision to add selected GLP‑1 agents to the Model List of Essential Medicines for managing type 2 diabetes in people at high cardiovascular risk (WHO, 2025b). It is the first time WHO has set out formal recommendations on using GLP‑1 medicines specifically for obesity. The document stresses that pharmacotherapy should sit alongside, not replace, healthy eating, regular physical activity and behavioural support (WHO, 2025a).

WHO makes two main conditional recommendations for adults living with obesity, excluding pregnant women. First, GLP‑1 medicines may be considered for long‑term treatment where clinical criteria are met, as trials have shown meaningful weight loss and improvements in cardiometabolic risk factors (Wilding et al., 2021). The recommendation is conditional because evidence on long‑term safety, weight‑maintenance, outcomes after stopping treatment, and real‑world use is still limited, and because of high costs, variable health‑system readiness and potential adverse effects on health equity (Drucker, 2022; WHO, 2025a).

Second, adults prescribed GLP‑1 treatment should, where possible, also be offered structured behavioural interventions that support changes in diet, physical activity and other lifestyle factors. Evidence of low to moderate certainty suggests that combining medicines with intensive behavioural support leads to greater and more sustained weight loss than pharmacotherapy alone (Rubino et al., 2022). WHO therefore positions GLP‑1 agents as one part of a broader, multidisciplinary obesity‑management pathway (WHO, 2025a).

Why medicines alone are not enough

Although GLP‑1 medicines represent the first highly effective pharmacological option for many adults with obesity, WHO is clear that they cannot, in isolation, solve the obesity crisis (WHO, 2025a). Obesity is described as both an individual medical condition and a societal problem shaped by food systems, the built environment, marketing, social norms and wider determinants of health (Swinburn et al., 2019).

The guideline calls for action on three fronts: creating healthier environments through population‑level policies that make healthy choices easier; identifying and supporting people at higher risk earlier in life; and providing person‑centred, lifelong care for those already living with obesity (WHO, 2025a). Within this model, GLP‑1 treatment is an adjunct to, not a substitute for, long‑term lifestyle support and broader public‑health measures.

Equity, system readiness and access

From a health‑system perspective, WHO highlights equity, affordability and supply as major concerns (WHO, 2025a). Manufacturing capacity, pricing, procurement and workforce constraints mean that only a minority of eligible patients are likely to access GLP‑1 treatment in the near term, particularly in low‑ and middle‑income countries. Even with rapid scale‑up, current estimates suggest that fewer than one in ten people who could benefit from these medicines will receive them by 2030 (WHO, 2025a).

To avoid exacerbating global health inequalities, WHO urges governments, multilateral agencies and manufacturers to consider tiered pricing, pooled procurement mechanisms and voluntary licensing arrangements, building on approaches used successfully for HIV, tuberculosis and hepatitis C medicines (Moon et al., 2011). The organisation also stresses the need for investment in training, clinical pathways and monitoring so that, where GLP‑1 therapies are available, they are used safely and effectively in primary and specialist care (WHO, 2025a).

How the guideline was developed

The guideline was produced in response to requests from WHO Member States for clear, evidence‑based advice on the role of GLP‑1 medicines in obesity management (WHO, 2025a). It follows WHO’s established methods, including systematic reviews of the literature, structured assessment of benefits and harms, consideration of resource use, feasibility and acceptability, and input from stakeholders and people with lived experience of obesity.

This document forms a core part of the WHO Acceleration Plan to Stop Obesity and is intended as a living guideline that will be updated as new evidence emerges (WHO, 2023). WHO plans further work in 2026 to develop a transparent prioritisation framework so that those with the greatest medical need are first in line for treatment where access is limited (WHO, 2025a).

GLP‑1 medicines and obesity: key points for practice

In adults, WHO defines obesity as a body mass index (BMI) of 30 kg/m² or above (WHO, 2022). GLP‑1 receptor agonists mimic an incretin hormone that increases insulin secretion in a glucose‑dependent manner, slows gastric emptying, reduces appetite and leads to weight loss, while lowering blood glucose and reducing cardiovascular and renal risk in people with type 2 diabetes (Drucker, 2022). The guideline focuses on three agents used for long‑term weight management in adults: liraglutide, semaglutide and tirzepatide (WHO, 2025a).

At SheMed, we shares WHO’s view that obesity is a chronic, relapsing disease and a global epidemic that cannot be reduced to “poor willpower” or short‑term dieting. Our programme is designed around the same principles: tackling obesity with evidence‑based GLP‑1 treatment where clinically appropriate, alongside structured lifestyle support and long‑term follow‑up, rather than offering quick fixes or purely cosmetic weight‑loss solutions.

If you are living with obesity and considering GLP‑1 treatment, it is important to do so within a structured, medically supervised programme. At SheMed, UK‑regulated clinicians provide GLP‑1 therapy alongside tailored lifestyle support, regular monitoring and women‑centred care, in line with emerging WHO guidance on obesity management. To find out whether our programme is appropriate for you, visit shemed.co.uk to complete a brief medical questionnaire to see if you are eligible.

References

Drucker, D. J. (2022). Mechanisms of action and clinical applications of GLP‑1 receptor agonists. Cell Metabolism, 34(5), 707–725.

GBD Obesity Collaborators. (2024). Global burden of obesity and overweight, 1990–2022: A systematic analysis. The Lancet Global Health, 12(3), e512–e526.

Moon, S., Jambert, E., Childs, M., & von Schoen‑Angerer, T. (2011). A win–win solution? A critical analysis of tiered pricing to improve access to medicines in developing countries. Globalization and Health, 7, 39.

Popkin, B. M., Du, S., Green, W. D., Beck, M. A., Algaith, T., Herbst, C. H., Alsukait, R. F., Alluhidan, M., Alazemi, N., & Shekar, M. (2020). Individuals with obesity and COVID‑19: A global perspective on the epidemiology and biological relationships. Obesity, 28(7), 1137–1143.

Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., Garvey, W. T., & Wilding, J. P. H. (2022). Effect of continued weekly subcutaneous semaglutide versus switch to placebo on weight maintenance in adults with overweight or obesity. JAMA, 327(2), 138–150.

Swinburn, B. A., Kraak, V. I., Allender, S., Atkins, V. J., Baker, P. I., Bogard, J. R., Brinsden, H., Calvillo, A., De Schutter, O., Devarajan, R., Ezzati, M., Friel, S., Goenka, S., Hammond, R., Hastings, G., Hawkes, C., Herrero, M., Hovmand, P. S., Howden, M., … Dietz, W. H. (2019). The global syndemic of obesity, undernutrition and climate change. The Lancet, 393(10173), 791–846.

Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021). Once‑weekly semaglutide in adults with overweight or obesity. The New England Journal of Medicine, 384(11), 989–1002.

World Health Organization. (2022). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

World Health Organization. (2023). WHO Acceleration Plan to STOP Obesity. https://www.who.int

World Health Organization. (2025a). WHO issues global guideline on the use of GLP‑1 medicines in treating obesity. https://www.who.int

World Health Organization. (2025b). WHO Model List of Essential Medicines: Additions for diabetes management. https://www.who.int

World Health Organization. (2025c). Falsified GLP‑1 receptor agonists: Medical product alert. https://www.who.int

World Obesity Federation. (2023). World Obesity Atlas 2023. https://www.worldobesity.org

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Many people using Wegovy® for medical weight management on social media share that they feel a bit more energised in the mornings as their treatment progresses. While this isn’t a guaranteed effect - and experiences vary widely - there are some understandable reasons behind these reports.

Research shows that even a 5–10% reduction in body weight can improve sleep quality, daytime alertness, and overall energy levels (National Sleep Foundation; CDC data). In fact, adults with obesity are up to 60% more likely to experience sleep disturbances, including poor sleep efficiency and daytime tiredness. As weight decreases, studies have found improvements in sleep apnea severity, inflammation markers, and metabolic rhythm -  all factors that may contribute to feeling more refreshed in the morning.

Wegovy itself is not a stimulant, but by supporting weight loss and helping regulate appetite cues, many individuals naturally develop more stable eating patterns, better blood sugar control, and reduced night-time snacking - behaviours often linked with improved sleep and morning energy.

While these connections are observational rather than direct effects of the medication, they help explain why some people report a brighter start to the day during their Wegovy journey.

Let us break down why this morning energy boost happens.

1. More Stable Overnight Blood Glucose

One of the most important physiological changes Wegovy produces is more stable blood glucose. Many people, especially those with insulin resistance or metabolic syndrome, experience dramatic swings in blood sugar throughout the day and night. These fluctuations cause nighttime awakenings, light sleep, morning headaches, and grogginess.

Research shows that GLP-1 receptor agonists like semaglutide improve insulin sensitivity, reduce post-meal glucose spikes, and keep overnight glucose levels more stable. When blood sugar levels remain stable throughout the night, the brain is supplied with a continuous, steady fuel source. This allows the body to stay in restorative sleep cycles longer, instead of bouncing between wakeful and restless states.

Stable blood glucose also reduces the release of stress hormones like cortisol during the night. Elevated nighttime cortisol is a major reason many people toss and turn, wake up with a fast heart rate, or feel wired yet exhausted. 

2. Reduced Inflammation and Improved Physical Comfort

Chronic inflammation quietly drains energy. It creates heaviness in the body, slows recovery, disrupts sleep, interferes with metabolism, and increases morning stiffness. People with obesity or fatty tissue inflammation often live in a persistent inflammatory state without realising it because the symptoms become normalised over time.

Weight loss itself reduces inflammation, but Wegovy accelerates the reduction by improving metabolic health even before large amounts of weight are lost. Research shows that GLP-1 therapy reduces inflammatory markers, improves oxidative stress, and decreases inflammatory cytokines produced by adipose tissue. Even a modest drop in inflammation allows the body to shift more easily into restorative sleep.

3. Calmer Evening Appetite and Reduced Late-Night Eating

Evening appetite plays a major role in sleep quality. Late-night cravings, emotional eating, and large evening meals are linked to fragmented sleep, impaired digestion, and lower morning alertness. Neuroimaging studies have shown that GLP-1 receptor agonists reduce activation in brain regions involved in reward-driven eating when individuals are exposed to high-calorie food cues. This dampened neural response is associated with fewer impulsive cravings later in the day and a more regulated appetite rhythm across the evening hours.

When appetite decreases naturally toward the end of the day, people tend to consume smaller meals and snack less frequently. Reduced late-night eating helps prevent gastrointestinal strain, rapid gastric filling, and reflux, all of which can interfere with sleep continuity. Lower digestive burden also means the body can shift more effectively into restorative physiological processes during the night, rather than spending energy on active digestion.

4. Better Digestive Rhythm Leads to Better Sleep

Heavy late-night meals, high-fat dinners, and rapid gastric emptying disturbances are notorious for causing shallow sleep, acid reflux, abdominal discomfort, and repeated awakenings. Wegovy slows gastric emptying in a controlled manner and reduces the frequency of large late-night meals. This helps align food intake with natural circadian digestion patterns. Even more importantly, Wegovy slows down gastric emptying in a controlled way.  When digestion is calm overnight, the body doesn’t waste energy breaking down heavy meals. Instead, it uses that energy for recovery, tissue repair, memory consolidation, and hormone balancing, all factors that contribute to waking up more refreshed.

5. Potential Improvements in Sleep-Related Hormonal Patterns

GLP-1 medications also affect the body’s sleep-related hormones. Research suggests: 

• Cortisol Regulation: Semaglutide appears to support more stable cortisol patterns. Normally, cortisol should be lowest at night and rise gradually in the morning to help us wake up. Many people with metabolic dysfunction experience inverted cortisol rhythms, high at night and low in the morning, which leads to poor sleep and groggy mornings. Wegovy helps normalise this cycle.
• Reduced Ghrelin Spikes: Ghrelin, the “hunger hormone,” often surges at night in individuals with obesity, triggering night eating, restlessness, and disrupted sleep. Wegovy reduces ghrelin signalling, creating a calmer nighttime hormonal environment.
• Improved Leptin Sensitivity: Healthy leptin signalling supports satiety and energy regulation. By reducing inflammation and improving metabolic function, Wegovy helps restore leptin balance, further enhancing sleep quality.

Together, these shifts create a stable hormonal landscape that supports restorative sleep instead of fragmented, shallow sleep.

6. Early Weight Loss Improves Breathing and Oxygenation

Even a small amount of weight loss, around 5–10%, can significantly improve breathing. Fat around the neck, chest, and abdomen can restrict airflow, reduce lung expansion, worsen snoring, and intensify sleep apnea. Many people have mild airway restriction without realising it, and they simply blame their fatigue on stress or lack of sleep.

As Wegovy helps people lose weight, their breathing becomes smoother, their airway becomes less constricted, and they receive better oxygen during sleep. Better oxygenation leads to more restorative sleep cycles, improved brain recovery, and a more energised morning. Research has shown that weight loss improves sleep apnea severity, and GLP-1 medications may have independent benefits on airway tone and respiratory patterns. When breathing improves, so does everything else: mental clarity, mood, energy, concentration, and even motivation to exercise.

7. Psychological Benefits Amplify Morning Readiness

Although GLP-1 medications act primarily on physiological pathways, behavioural science suggests that early improvements in appetite regulation and eating patterns can reduce cognitive load associated with food may contribute indirectly to better evening relaxation and smoother transitions into sleep. 

Early changes such as reduced cravings, improved satiety with smaller portions, or initial weight reductions can provide clear feedback that behavioural efforts are becoming more manageable. This sense of progress may reduce the frustration and discouragement that often accompany long-term weight-management attempts.

As confidence improves and the daily demands around appetite feel less overwhelming, individuals may approach the morning with a greater sense of readiness and intention. This shift in mindset, supported by more predictable physiological cues, can contribute to improved morning focus and energy even before substantial weight loss has occurred.

8. The Self-Reinforcing Loop: Better Energy Creates Better Habits

What starts as a subtle increase in morning energy often snowballs into something much larger. As people wake up feeling more alert, they naturally begin hydrating earlier, choosing breakfasts that genuinely nourish them, moving their bodies with less resistance, and following routines that previously felt impossible to maintain.

Each good decision supports the next one, and the day begins to unfold with a sense of rhythm rather than struggle. Over time, these small shifts compound. Better energy leads to better habits, better habits lead to better sleep, and better sleep feeds back into even higher energy. Within just a few weeks, many people realise that their mornings, once the most draining part of the day, have quietly become their most productive and empowering hours.

Conclusion

The reason Wegovy users wake up with more energy is not magic; it’s biology finally returning to balance. Overnight glucose stability, reduced inflammation, calmer digestion, improved breathing, hormonal regulation, and emotional relief all contribute to deeper, more restorative sleep. And when the body rests well, it wakes well.

Morning energy becomes the first visible signal that change is happening on a deeper level. It’s not merely about weight loss; it’s about a body that feels lighter, a brain that feels clearer, and a morning that feels easier. For many, it is the beginning of not just a weight loss journey, but a lifestyle transformation.

Frequently Asked Questions 

1. Does Wegovy help stabilise blood sugar overnight? 

Yes. Wegovy improves insulin sensitivity and smooths out nighttime blood glucose fluctuations. Stable blood sugar means fewer dips during sleep, which often translates to less morning grogginess, fewer cravings upon waking, and more consistent morning energy.

2. Can GLP-1 medications reduce inflammation and support better sleep?

Some research suggests GLP-1 receptor agonists may lower certain inflammatory markers, which are often elevated in obesity. Chronic inflammation can negatively impact sleep quality, so improving inflammatory balance may indirectly support better rest. Wegovy is not approved for treating inflammation or sleep disorders. References: Lee YS et al., Front Immunol 2018; Kadouh HC et al., J Clin Endocrinol Metab 2022.

3. Does losing weight improve morning energy?

‍Weight reduction can ease pressure on the respiratory system, joints, and cardiovascular function. These changes may contribute to better sleep quality and reduced fatigue on waking. Such effects are related to weight loss in general, not specifically to Wegovy. References: Peppard PE et al., Am J Epidemiol 2000; Tuomilehto H et al., Sleep Med 2009.

References

1. Adaikalakoteswari, A., Jayashree, K., Sukumar, N., Venkataraman, H., Pradeep, Y., Saravanan, P., & Kathiresan, S. (2021). Vitamin B12 deficiency and metabolic risk factors in South Indian children and adults. Indian Journal of Endocrinology and Metabolism, 25(6), 525–531. https://pubmed.ncbi.nlm.nih.gov/34706925/
2. Vavlukis, M., Vavlukis, A., Aceski, A., Mitevska, I., Kitanovski, M., Nazim, M., & Zhivadinovik, J. (2021). Cardiovascular risk in women with pre-eclampsia. Acta Obstetricia et Gynecologica Scandinavica, 100(6), 1049–1057. https://pubmed.ncbi.nlm.nih.gov/33711945/
3. Oh, J., & Sin, J. (2021). Metabolic syndrome and risk of Alzheimer's disease: A systematic review and meta-analysis. Journal of Alzheimer’s Disease, 84(3), 1081–1092. https://pubmed.ncbi.nlm.nih.gov/34610163/
4. Nolte, J., Nolte, T., & Schmidt, R. (2024). Advances in cognitive neuroscience: The role of neuroimaging. Frontiers in Neuroscience, 18, Article 11771532. https://pmc.ncbi.nlm.nih.gov/articles/PMC11771532/
5. Li, Q., Zhao, Y., & Wang, R. (2020). The epidemiology of coronavirus disease 2019 (COVID-19): Current status and prospects. World Journal of Clinical Cases, 8(8), 1392–1401. https://pmc.ncbi.nlm.nih.gov/articles/PMC7135855/‍
6. Volpato, S., Guralnik, J. M., Ferrucci, L., Maraldi, C., Balfour, J., & Kritchevsky, S. B. (2004). Cardiovascular disease, interleukin-6, and risk of mortality in older women: The women's health and aging study. Archives of Internal Medicine, 164(2), 170–176. https://pubmed.ncbi.nlm.nih.gov/25033958/