OZEMPIC, GLP-1 AGONISTS, AND THE NEGATIVE OUTCOMES NO ONE TALKS ABOUT

INTRODUCTION Over the last few decades, humanity has faced an explosion of overweight, obesity, and diabetes type-2 resulting in chronic metabolic diseases and the loss of about 20 years of your lifespan. Today, 47% of the global population is overweight, 15% obese, and every year another batch of 22 million people join the club of diabetes patients (GBD 2023, Phelps et al. 2024). One of the major contributors to mass epidemics is the consumption of ultra-processed foods, seed oils, a lack of nutrients, and the absence of whole foods in the diet. These lead to chronic low-grade inflammatory processes that disrupt your intestinal and hormonal systems (Askari et al. 2020, Nardocci et al. 2021). For the firm believers in Western medicine, the answer to this problem is always the same: a pill will cure me! However, in most cases, it does nothing more than mask the symptoms, and your suppressed disease continues to flourish and destroy your body. GLP-1 agonists (glucagon-like peptide-1 receptor agonists) are promoted as a game-changer. A class of drugs regulating blood sugar and able to counteract overweight, at least to some extent, has all the potential of becoming the next bestseller (Nauck & Meier 2018). The drugs with generic names as tirzepatide (Mounjaro), semaglutide (Ozempic, Wegovy), and liraglutide (Victoza, Saxenda) are the most well-known. These GLP-1 agonists mimic the GLP-1 hormone, tricking your body into producing more insulin to counter high blood sugar levels, slow down stomach transit, inhibit glucagon, and consequently diminish cravings and hunger (Wilding et al. 2021, Karagiannis et al. 2022). One may wonder, with an already inflamed and/or dysfunctional pancreas (the insulin factory of your body), forcing this organ to produce above its natural status may lead to unexpected consequences in the long run. As in many of these drug studies, these data remain absent or under-researched. THE FIRST CRACKS IN THE WALL!! Although the drugs are relatively new on the market, the first safety risks and side effects are already being published in medical journals, and many are sure to follow, considering most studies limit their follow-up period to 12 weeks (Yao et al. 2024), and mid- and long-term outcomes are still under investigation (Moiz et al. 2025). Frequently Reported Side-Effects Gastrointestinal complaints : nausea, vomiting, diarrhea, and constipation occur in 30–50% of users, especially during the initial phase (Marso et al. 2016). These complaints often decrease over time but lead to discontinuation of treatment in 10% of cases (Davies et al. 2018). Headache and fatigue : Approximately 10–15% of patients report these symptoms (Nauck & Meier 2018). Hypoglycemia : Particularly when combined with sulfonylureas or insulin, with a risk of up to 10% (Marso et al. 2016). Gallbladder issues : A review study reports gallbladder problems in 55% of GLP-1 patients leading to more digestive issues (Yao et al. 2025). Vision impairment : In a group of 60,000 patients, up to 3-times higher incidence of ischemic optic neuropathy (obstruction of blood flow in the eye, resulting in vision loss) was observed (Simonsen et al. 2025). Vitamin and mineral deficiencies : Essential deficiencies, primarily in vitamin D and iron, were identified in 20% of GLP-1 users. These are important for a well-functioning immune response, hormonal system, and to prevent anemia (Scott Butsch et al. 2025). Looking good so far? There is more to come: Other Reported Severe Complications Pancreatitis : Observational studies suggest up to a two-fold increased risk of pancreatic inflammation (odds ratio 1.4–2.0) (Monami et al. 2017). Thyroid cancer : Preclinical studies in rodents showed a risk of medullary thyroid cancer, but human data are inconclusive. Caution is advised in patients with a history of thyroid cancer (Montero & Maraka 2024, Moiz et al. 2025). Gastrointestinal obstruction : Recent reports indicate a rare risk of ileus or gastric paralysis, particularly with longer-term use (Sodhi et al. 2023). Relapse after discontinuation : Weight regain often occurs after stopping treatment, with 60–80% of patients regaining part of the lost weight within a year (Wilding et al. 2021). Muscle loss : Up to 40% of weight loss with GLP-1 agonists may involve muscle mass (consisting of muscle cells, muscle fluid, and muscle proteins) (Sargeant et al. 2022, Tinsley & Heymsfield 2024). BALANCING THE SIDE-EFFECTS! The use of GLP-1 agonists can lead to complications, so much is clear. Follow-up research suggests supporting GLP-1 agonist treatment with increased protein intake and guided strength training to counteract muscle decline in all patients (Tinsley & Heymsfield 2024). This in itself won’t counter the other potential side effects. We may ask ourselves how these GLP-1-agonists contribute to enhancing quality of life when you need another plethora of measures to minimise safety risks. Wouldn’t it be better to address the root causes? YOUR SOLUTION: THE KETOGENIC DIET AND INTERMITTENT FASTING! The ketogenic diet (KD) is a very low-carbohydrate diet (5–10% of energy intake, usually <50 g/day), high in fats (70–80%), and moderate in proteins (15–20%). It induces ketosis, where the body breaks down fats into ketones as an alternative energy source instead of glucose (Paoli et al. 2018). In the long term, it can be combined with or replaced by the Mediterranean diet and/or intermittent fasting to sustain positive results (Cuevas-Cervera et al. 2022). A typical ketogenic diet includes fatty fish (salmon, mackerel), avocado, olive oil, coconut oil, nuts, seeds, eggs, red grass-fed meat, full-fat dairy, and low-carb vegetables (broccoli, spinach, zucchini). Be aware of potential micro-and nano plastics in seafood which in turn may pose a risk. Sugar, grains, bread, pasta, rice, potatoes, and most fruits should be avoided. Fruits can be reintroduced later on in the dietary process. Benefits of the Ketogenic Diet The KD promotes fat burning through reduced insulin levels and increased satiety, leading to a weight loss up to 10kg within 6 weeks (Patikorn et al. 2023). The diet lowers HbA1c (average blood sugar) by 0.5–1.5% and can reduce insulin requirements by 50–75% in type-2 diabetics (Westman et al. 2020). A very recent study shows that combining a ketogenic diet with intermittent fasting (IF) can even lead to the complete remission of type 2 diabetes (Zhou et al. 2024). Studies show that 60–90% of type 2 diabetes patients can reduce or discontinue medication when following KD and/or IF (Hallberg et al. 2018, Zhou et al. 2024). The KD lowers markers such as C-reactive protein (CRP), reducing cardiovascular risks and minimizing low-grade inflammation throughout the body (Forsythe et al. 2018). Also, improved insulin sensitivity and brain function are noticed as ketones function as a stable energy source, protecting against cognitive decline (Paoli et al. 2018). The initial duration for following the KD varies from one to six months, depending on the intended goals. Over the long term, it is advisable to follow a tailored diet under guidance, which may include a combination of partial keto, Mediterranean diet, and intermittent fasting, alongside sufficient physical activity. This approach can lead to a weight loss of up to 20 kg in a few months and significantly reduce insulin resistance. The Westman et al. study (2020) compared the ketogenic diet (KD) with standard care (including medication) and found that the KD was superior in lowering HbA1c and body weight, with fewer side effects (Westman et al. 2020). In the long term, these health benefits can be maintained when KD, IF, and exercise become part of a renewed lifestyle (Firman et al. 2023, Markovikj et al. 2023). This doesn’t mean you can’t sin every now and then, as your body will become more resilient to withstand some challenges. An 80/20 rule may help as a guide in this context once the goals have been reached. When you want to take back control of your health, the KD diet is a good start! Nonetheless, it may be a challenge for some, and, therefore, it is advisable to seek guidance from a health professional acquainted with the matter, as you may experience the ‘keto flu’ when you are a novice to this diet. It’s nothing more than your body restoring its settings, and may present itself as minor flu-like symptoms. These resolve within a few days. CONCLUSION GLP-1 agonists such as semaglutide, liraglutide, and tirzepatide are powerful tools for treating type 2 diabetes and obesity, with significant improvements in blood sugar and body weight. However, side effects such as gastrointestinal complaints, risks of pancreatitis, thyroid issues, muscle loss, and weight regain after discontinuation make them less ideal for long-term use. Additionally, the long-term side effects of GLP-1 agonists are not yet sufficiently understood. The ketogenic diet offers a robust alternative, with comparable benefits in glycemic control and weight loss, but without the severe side effects and with additional advantages such as anti-inflammatory effects and reduced medication dependency. Scientific studies demonstrate that the KD is safe and effective, though it requires discipline and guidance. For those seeking a sustainable, natural approach, the ketogenic diet is a valuable option to improve metabolic health and reduce reliance on medication. Start with small steps, consult a professional, and discover how lifestyle changes can transform your health. REFERENCES ASKARI, M., HESHMATI, J., SHAHINFAR, H., TRIPATHI, N. & DANESHZAD, E. 2020. Ultra-processed food and the risk of overweight and obesity: a systematic review and meta-analysis of observational studies. International Journal of Obesity, 44, 2080-2091. CUEVAS-CERVERA, M., PEREZ-MONTILLA, J. J., GONZALEZ-MUÑOZ, A., GARCIA-RIOS, M. C. & NAVARRO-LEDESMA, S. 2022. The effectiveness of intermittent fasting, time restricted feeding, caloric restriction, a ketogenic diet and the mediterranean diet as part of the treatment plan to improve health and chronic musculoskeletal pain: a systematic review. International Journal of Environmental Research and Public Health, 19, 6698. DAVIES, M.J., D’ALESSIO, D.A., FRADKIN, J., et al. (2018) 'Management of hyperglycemia in type 2 diabetes, 2018: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)', Diabetes Care, 41(12), pp. 2669–2701. FIRMAN, C. H., MELLOR, D. D., UNWIN, D. and BROWN, A. (2024) 'Does a Ketogenic Diet Have a Place Within Diabetes Clinical Practice? Review of Current Evidence and Controversies', Diabetes Therapy, 15, pp. 77–97. FORSYTHE, C.E., et al. (2018) 'Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation', Nutrition, 47, pp. 65–70. GBD 2021 Diabetes Collaborators (2023) 'Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021', The Lancet, 402, pp. 1–18. HALLBERG, S.J. et al. (2018) 'Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study', Diabetes Therapy, 9(2), pp. 583–612. doi:10.1007/s13300-018-0373-9. KARAGIANNIS, T., et al. 2022. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia, 65(8), pp.1251-1261. MARKOVIKJ, G., KNIGHTS, V. & KLJUSURIĆ, J. G. 2023. Ketogenic Diet Applied in Weight Reduction of Overweight and Obese Individuals with Progress Prediction by Use of the Modified Wishnofsky Equation. Nutrients, 15, 927. MARSO, S.P., DANIELS, G.H., BROWN-FRANDSEN, K., et al. (2016) 'Liraglutide and cardiovascular outcomes in type 2 diabetes', New England Journal of Medicine, 375(4), pp. 311–322. MOIZ, A., FILION, K. B., TSOUKAS, M. A., YU, O. H. Y., PETERS, T. M. & EISENBERG, M. J. 2025. The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions. eClinicalMedicine, 86. MONAMI, M., NARDINI, C., MANNUCCI, E. (2017) 'GLP-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials', Diabetes Research and Clinical Practice, 123, pp. 189–197. MONTERO, A. & MARAKA, S. (2024) 'GLP-1 receptor agonists: current and future perspectives in obesity and diabetes management', Endocrine Reviews, 45(2), pp. 245–262. NARDOCCI, M., POLSKY, J. Y. & MOUBARAC, J.-C. 2021. Consumption of ultra-processed foods is associated with obesity, diabetes and hypertension in Canadian adults. Canadian Journal of Public Health, 112, 421-429. NAUCK, M.A. & MEIER, J.J. (2018) 'Incretin hormones: their role in health and disease', Diabetes, Obesity and Metabolism, 20(Suppl 1), pp. 5–21. doi:10.1111/dom.13129. PAOLI, A., RUBINI, A., VOLEK, J.S., et al. 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(2022) 'Effects of GLP-1 receptor agonists on body composition: a systematic review', Obesity Reviews, 23(5), e13425. SCOTT BUTSCH, W., SULO, S., CHANG, A. T., KIM, J. A., KERR, K. W., WILLIAMS, D. R., HEGAZI, R., PANCHALINGAM, T., GOATES, S. & HEYMSFIELD, S. B. 2025. Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: A retrospective observational study. Obes Pillars, 15, 100186. SIMONSEN, E., LUND, L. C., ERNST, M. T., HJELLVIK, V., HEGEDÜS, L., HAMANN, S., JØRSTAD, Ø. K., GULSETH, H. L., KARLSTAD, Ø. & POTTEGÅRD, A. 2025. Use of semaglutide and risk of non‐arteritic anterior ischemic optic neuropathy: A Danish–Norwegian cohort study. Diabetes, Obesity and Metabolism, 27, 3094-3103. SODHI, M., REZAEIANZADEH, R., KEZOUH, A., et al. (2023) 'Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss', JAMA, 330(18), pp. 1795–1797. TINSLEY, G. M. & HEYMSFIELD, S. B. 2024. 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