The Rise and risks of Ozempic

Nearly 75% of US adults are overweight or obese, and 40% have pre-diabetes or diabetes. This widespread issue has led to increased interest in medications like Ozempic (Semaglutide), a GLP-1 (glucagon-like peptide-1) receptor agonist.

Ozempic mimics the hormone GLP-1, which regulates blood sugar by stimulating insulin secretion and inhibiting glucagon release. It also slows digestion, increasing feelings of fullness and reducing caloric intake. This dual action helps improve glycemic control and can aid in weight loss. Efficacy varies among individuals; about 20% of users may not lose weight or may even gain weight. This is likely due to the fact that while for many people Ozempic reduces appetite, for some individuals Ozempic may lead to blood sugar that is too low, a condition known as hypoglycemia, which can increase cravings for carbohydrates and sugar.​

ozempic side effects

Ozempic has shown significant benefits for many, but it is not without risks. Known side effects include kidney damage, gastroparesis, gallbladder issues, muscle loss, nutrient deficiencies, thyroid cancer, and mental health concerns, including depression and increased suicidal ideation. Importantly, Ozempic is FDA-approved only for Type 2 Diabetes, not for weight loss.

​When discontinuing Ozempic, rapid weight gain, often termed "Ozempic rebound," is common. Studies show that within a year of stopping, two-thirds of users regain the lost weight, often ending up with a higher body fat percentage due to muscle loss (leads to lowered metabolic rate), poor dietary and lifestyle factors, and metabolic inhibition due to calorie restriction. ​

"With...[GLP-1]...treatments, there is a concomitant reduction in lean body mass, which seems to be in the range of 25%–40% of total weight loss." In other words, studies show that upwards of 40% of the weight lost on Ozempic isn’t the fat you’re hoping to bid adieu to – it’s muscle!

Additional Risks of Ozempic

• Pancreatitis (inflammation of pancreas): 9.09 times higher risk.
• Bowel Obstruction: 4.22 times higher risk.
• Gastroparesis (stomach paralysis): 3.67 times higher risk.
• Adipogenesis: Recent studies suggest that GLP-1 agonists can increase adipogenesis, the creation of new fat cells. While this might seem counterintuitive for weight loss, it emphasizes the importance of combining medication with lifestyle changes.
• Autoimmune Reactions: There have been reports of semaglutide-induced lupus erythematosus, which can involve multiple organs.
  
• Respiratory Risks: Some patients on semaglutide have experienced pulmonary aspiration of gastric contents.
  
• ​Appendicitis Risk: Emerging evidence suggests that GLP-1 receptor agonists, like Ozempic, may increase the risk of appendicitis.
  

Safety trial duration on Ozempic lasted only 30-68 weeks, so safety for use beyond this timeframe has not been evaluated.

​The Real Culprits of Obesity

The obesity crisis is not due to a lack of injectable medications. The primary contributors are:

1. Sedentary Lifestyles: Modern conveniences and technology have led to reduced physical activity.
2. Processed Food Dominance: Highly processed foods, rich in sugars and unhealthy fats, dominate diets.
3. Environmental Toxins: Exposure to certain chemicals can disrupt metabolism and lead to weight gain.
4. Chronic Stress: Stress increases cortisol levels, leading to fat storage and weight gain.
5. Sleep Deprivation: Lack of sleep disrupts hormones that regulate hunger and metabolism.

learn more about obesogens

Natural Alternatives to GLP-1 agonists

For those seeking alternatives or aiming to prevent post-Ozempic weight gain, lifestyle changes are crucial. Natural ways to boost GLP-1 include:

1. Regular Exercise: 3-4 times per week, focusing on strength training.
2. Dietary Adjustments: Increase protein (0.8-1.0 g/lb of lean body mass per day) and fiber (at least 25g per day).
3. Stress Management and Sleep: Control cortisol levels by managing stress and ensuring 7-9 hours of sleep per night.
4. Probiotic Foods: Include fermented foods like kimchi, sauerkraut, yogurt, and kombucha. Taking probiotic supplements like Akkermansia, Clostridium butyricum, and Bifidobacterium infantis can naturally boost GLP-1. Pendulum’s GLP-1 probiotic is specifically formulated for this purpose.
5. Supplements: Consider GLP-1 boosting supplements like L-Glutamine, Berberine, Magnesium, curcumin, Ceylon cinnamon, and Resveratrol.
6. Appetite-Satiating Compounds: Supplements like Calocurb, which uses a hops extract, can significantly increase GLP-1 levels.
7. Lifestyle Modifications: Regular fasting (16-18 hours of fasting per day)
8. Ketones: Utilizing ketone supplements like KetoneIQ or KetoneAid can suppress the hunger hormone ghrelin, aiding in appetite control.

Peptides for Weight Loss and Muscle Gain

For those seeking more advanced methods, peptides can be a powerful tool with fewer side effects than GLP-1 agonists. Some effective peptides include:

1. IGF-1 LR3: Increases muscle by stimulating hyperplasia.
2. Ipamorelin: Enhances muscle growth and suppresses hunger by increasing growth hormone secretion.
3. CJC-1295: Promotes fat loss and muscle protein synthesis by increasing IGF-1 and functioning as a growth hormone-releasing hormone.
4. Tesamorelin: Reduces visceral fat and stimulates muscle protein production.
5. 5-Amino-1MQ: Blocks NNMT, an enzyme linked to obesity, facilitating fat reduction and providing clean energy.

For injectable peptides, I recommend the companies Limitless Life or Peptide Sciences. If you're looking for quality oral peptide formulations, check out LVLUP Health.
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Also, it’s important to understand that the best effects from any of the peptides listed above come via pairing them with a consistent weight training routine, adequate protein intake, and a physically active lifestyle. 
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​While Ozempic has been demonstrated to mitigate blood sugar control and weight management, it's essential to weigh these against potential risks and side effects. Incorporating lifestyle changes and considering natural alternatives can help mitigate these risks and support long-term health. Natural alternatives and peptides can provide effective, safer options for achieving weight loss and muscle gain. Combining these with lifestyle changes is crucial for long-term success. Addressing the root causes of obesity through lifestyle changes is crucial for long-term health. Prioritizing physical activity, a balanced diet, reducing exposure to toxins, managing stress, and ensuring adequate sleep can significantly impact overall well-being and weight management.

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references

Wadden, Thomas A. et al. “The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities.” Current Obesity Reports 12 (2023): 453 - 473. https://doi.org/10.1007/s13679-023-00534-z.
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Castellanos, Vanessa, et al. “Semaglutide-Induced Lupus Erythematosus with Multiorgan Involvement.” Cureus, vol. 16, no. 3, 1 Mar. 2024, p. e55324, pubmed.ncbi.nlm.nih.gov/38559525/, https://doi.org/10.7759/cureus.55324. 

Billings, Sabrina A., et al. “Rhabdomyolysis Associated with Semaglutide Therapy: A Case Report.” Cureus, vol. 15, no. 12, 1 Dec. 2023, p. e50227, pubmed.ncbi.nlm.nih.gov/38192938/, https://doi.org/10.7759/cureus.50227. 

Li, J, et al. “Case Report: Semaglutide-Associated Depression: A Report of Two Cases.” Frontiers in Psychiatry, vol. 14, 29 Aug. 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC10495976/#:~:text=At%20present%2C%20most%20reported%20adverse, https://doi.org/10.3389/fpsyt.2023.1238353.

Casella, Sarah, and Katelyn Galli. “Appendicitis: A Hidden Danger of GLP-1 Receptor Agonists?” ˜the œJournal of Pharmacy Technology, vol. 40, no. 2, 7 Dec. 2023, pp. 108–111, https://doi.org/10.1177/87551225231216638. 

Challa, Tenagne Delessa, et al. “Regulation of Adipocyte Formation by GLP-1/GLP-1R Signaling.” Journal of Biological Chemistry, vol. 287, no. 9, Feb. 2012, pp. 6421–6430, https://doi.org/10.1074/jbc.m111.310342. 

Willoughby, Darryn, et al. “Body Composition Changes in Weight Loss: Strategies and Supplementation for Maintaining Lean Body Mass, a Brief Review.” Nutrients, vol. 10, no. 12, 3 Dec. 2018, p. 1876, www.ncbi.nlm.nih.gov/pmc/articles/PMC6315740/, https://doi.org/10.3390/nu10121876.

Wilding, John P. H., et al. “Weight Regain and Cardiometabolic Effects after Withdrawal of Semaglutide: The STEP 1 Trial Extension.” Diabetes, Obesity and Metabolism, vol. 24, no. 8, 19 May 2022, pp. 1553–1564, pubmed.ncbi.nlm.nih.gov/35441470/, https://doi.org/10.1111/dom.14725.

Leehey, David J., et al. “Acute Kidney Injury Associated with Semaglutide.” Kidney Medicine, vol. 3, no. 2, Mar. 2021, pp. 282–285, https://doi.org/10.1016/j.xkme.2020.10.008.

Bezin, Julien, et al. “GLP-1 Receptor Agonists and the Risk of Thyroid Cancer.” Diabetes Care, vol. 46, no. 2, 10 Nov. 2022, https://doi.org/10.2337/dc22-1148.