The quest for effective weight loss solutions has led to significant advancements in medical science, with GLP-1 agonists such as semaglutide (marketed under names like Ozempic®) emerging as powerful tools. While these medications have revolutionized treatment with their effectiveness, their accessibility issues, cost, and potential side effects prompt a deeper exploration of alternative solutions.

While pharmaceuticals are NOT my area of expertise and fall outside my professional domain, I was nonetheless compelled to explore the advantages and disadvantages of these drugs. The purpose of this blog was to navigate through the sea of information available and uncover more natural alternatives, thereby providing readers with knowledge and choices.

What is GLP-1

So What Exactly is GLP-1? Understanding GLP-1 Agonists

GLP-1, short for Glucagon-Like Peptide-1, is a crucial hormone in the body’s metabolic regulation, playing a significant role in maintaining glucose homeostasis and appetite control. Produced in the intestines in response to food intake, GLP-1 stimulates insulin secretion from the pancreas when glucose levels are high, inhibits glucagon release (thereby reducing glucose production by the liver) and slows gastric emptying to promote satiety. Its actions are integral to maintaining blood glucose levels within a normal range and contribute to appetite regulation.

GLP-1 agonists are a class of medications that mimic the action of the naturally occurring GLP-1 hormone. These drugs are used primarily in the treatment of type 2 diabetes and, due to their effects on appetite and weight, have also been found to be beneficial in weight management. (1)

Semaglutide (Ozempic®, Wegovy®) is a prominent example of a GLP-1 agonist. By activating GLP-1 receptors, semaglutide enhances insulin secretion in a glucose-dependent manner, similar to the actions of natural GLP-1. However, semaglutide has a much longer duration of action than endogenous GLP-1, primarily due to its structural modifications that make it resistant to degradation by the enzyme DPP-4 (dipeptidyl peptidase-4) and enable it to bind more effectively to the GLP-1 receptor. Natural GLP-1 has a very short half-life, being rapidly degraded by enzymes in the blood, which limits its utility as a therapeutic agent without modification. (2)

Semaglutide is designed to resist this rapid degradation, providing prolonged action. GLP-1’s physiological role encompasses a broad range of metabolic processes, while semaglutide is specifically used as a medication to mimic these effects for therapeutic purposes in the treatment of type 2 diabetes and obesity.

Benefits, Risks, and Considerations

The primary benefit of GLP-1 agonists lies in their dual action of improving glycemic control and promoting weight loss. This makes them particularly valuable for individuals with type 2 diabetes who are also overweight or obese. Studies have shown that GLP-1 agonists can lead to significant weight loss, often exceeding that achieved through lifestyle changes alone. (3) Additionally, they have been associated with improvements in various cardiovascular risk factors, such as blood pressure and lipid profiles. 

While beneficial to some, there is a growing concern about their misuse. 

Medications like Ozempic® have seen a surge in off-label use by individuals who do not medically qualify as obese or diabetic, but rather those seeking a shortcut for weight loss. It’s important to understand that these drugs are not designed for the purpose of shedding a modest amount of weight, like those ‘stubborn’ last 20 or 30 pounds.

Healthcare providers and patients alike must prioritize a holistic approach to weight management, focusing on sustainable lifestyle changes such as diet and exercise, rather than depending solely on pharmacological solutions that may not be appropriate for their specific circumstances. However, for individuals facing significant weight challenges, particularly those who are morbidly obese and at risk of related health complications, incorporating medical interventions like GLP-1 agonists can be a crucial component of a strategy designed to initiate weight loss and reduce obesity-related risks.

While the benefits are compelling, potential side effects and long-term risks must be considered. 

Common gastrointestinal issues include nausea, vomiting, diarrhea, and constipation, which can affect patient compliance. Although rare, there is a risk of pancreatitis, gastroparesis, and patients with a history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 are advised against using GLP-1 agonists due to an increased risk of thyroid tumors. (4) Additionally, there are possible implications for those with a history of diabetic retinopathy. It’s also important to note that while GLP-1 agonists facilitate weight loss, the composition of the weight lost can include both fat and muscle mass. Loss of muscle mass, in particular, is a concern as it can be a driver of increased all-cause mortality that impacts overall health and physical function. These medications should be used only under medical guidance and integrated into a broader strategy that includes lifestyle modifications for long-term health improvement.

Increase GLP-1 Naturally

Stimulating the natural production of GLP-1 is a strategic approach to improving metabolic health, managing blood sugar levels, and supporting weight loss. Here are effective, natural strategies to boost GLP-1 levels:

High-Fiber Foods: Consume a diet high in fibre. Foods like chicory root, Jerusalem artichoke, garlic, onions, and leeks are particularly beneficial because they contain inulin, a type of soluble fibre that promotes gut health and stimulates GLP-1 production.

Protein-Rich Foods: Diets high in protein from both plant and animal sources have been shown to increase GLP-1 levels. Incorporate plenty of animal-based protein sources (meat, fish, eggs) and plant-based proteins such as lentils and beans. Aim to consume 1 gram of protein per pound of body weight each day. (5)

Healthy Fats: Monounsaturated and polyunsaturated fats, found in nuts, seeds, avocados, and oily fish, can also encourage GLP-1 release. Omega-3 fatty acids, in particular, have been linked to enhanced GLP-1 production. (6)

Regular Physical Activity: Exercise has a positive impact on GLP-1 levels. Both aerobic exercises, like jogging and cycling, and resistance training can increase the secretion of GLP-1, improving glucose tolerance and insulin sensitivity. (7)Weight training 3 to 4 times per week is vital to preserve muscle mass during weight loss.

Adequate Sleep:  Poor sleep has been associated with decreased levels of GLP-1. Ensure sufficient sleep (7-9 hours per night) and maintain a regular sleep hygiene routine.

Apple Cider Vinegar: Some studies suggest that vinegar can increase feelings of fullness and boost GLP-1 levels, especially when consumed with a carbohydrate-rich meal. (8)

Eating Slowly: Taking time to chew food thoroughly and eating meals without rushing can enhance GLP-1 release. Mindful eating practices help in better digestion and can trigger the secretion of GLP-1, contributing to improved satiety and reduced calorie intake.

Mindfulness and Relaxation Techniques: Chronic stress can negatively affect GLP-1 levels. Engaging in stress-reduction techniques such as meditation, yoga, or deep breathing exercises can help maintain healthy levels of GLP-1.

Additional Strategies For Enhanced Weight Loss

Probiotics and Gut Health: Incorporating specific probiotic strains, such as those from the Lactobacillus and Bifidobacterium families, can have a beneficial impact on weight management. These probiotics may positively alter the gut microbiota, which in turn can enhance metabolic health and support weight loss efforts.

Akkermansia Muciniphila: This specific gut bacterium has garnered attention for its potential role in improving metabolic health and supporting weight loss. It thrives on the mucin layer in the gut and has been associated with improved glucose metabolism and reduced fat storage. (9)

Intermittent-Fasting

Intermittent Fasting: Fasting strategies, including intermittent fasting, can complement the action of GLP-1 by promoting insulin sensitivity and further aiding in weight management. Fasting periods can enhance hormonal balance, encouraging the body to utilize stored fat for energy.

Spotlight on DNF-10®—A Promising Alternative to GLP-1 Agonists

Amid the plethora of products marketed for weight management, DNF-10® stands out for its ability to modulate dietary behaviours and metabolic processes, particularly influencing the sensation of fullness and appetite regulation. Its action mechanism focuses on the hypothalamus, an area of the brain that modulates our food intake and balances hunger-related hormones.

Derived from Saccharomyces cerevisiae (aka brewer’s yeast)—known for its many health benefits, including supporting digestive health, boosting the immune system, and being a rich source of essential nutrients like B vitamins and antioxidants, DNF-10® is a specialized hydrolysate fraction that targets the complex communication pathways between the gut and the brain. (10) It acts on the gut-brain mediators of satiety, to lower calorie intake and reduce body fat mass. 

The effectiveness of DNF-10® in promoting weight loss and improving signals of satiety has been substantiated through several clinical trials, with benefits observable within the first few weeks of supplementation. A daily dosage of 500 mg is recommended to harness the full potential of DNF-10® in regulating appetite and assisting in weight management efforts. (11)

While I haven’t personally tested each product listed below, they come from companies with strong reputations in the biohacking community. For those interested in exploring the benefits of DNF-10 for themselves, consider the following supplements:

  • Integrative Peptides—Can’t Weight: This product offers a simple yet effective formula that combines DNF-10 with Garcinia Cambogia, aiming to enhance satiety and support weight management efforts. 
  • Healthgevity—Ignite Plus: For a more comprehensive approach, Ignite Plus pairs DNF-10 with components designed to stabilize blood sugar and boost metabolism, providing a multifaceted strategy for weight loss.
  • Level Up Health—Total Recomp: This extensive formula includes not only DNF-10 but also a variety of metabolic support ingredients, making it a robust option for those looking to comprehensively tackle weight management. 

Each of these products leverages the potent effects of DNF-10, offering unique combinations and approaches to suit different health and weight management goals.

A Balanced Approach to Weight Management

The temptation of a straightforward fix to weight loss is understandably appealing, but it’s vital to recognize that true, lasting health extends beyond the confines of a single pill. As we navigate the potential of GLP-1 agonists and investigate alternative solutions, integrating these innovations with core health practices becomes indispensable. This approach entails looking past short-term fixes to evaluate the long-term effects of our everyday habits and decisions. Embracing a nutritious diet, committing to regular physical activity, securing quality sleep, and effectively managing stress are fundamental pillars of sustainable health. For those considering GLP-1 agonists, it’s widely acknowledged among health professionals that adopting a high-protein diet and engaging in strength training are crucial strategies for maintaining muscle mass.

In-text References

  1. Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151/
  2. Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ, Stemmer K, Tang-Christensen M, Woods SC, DiMarchi RD, Tschöp MH. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019 Dec;30:72-130. doi: 10.1016/j.molmet.2019.09.010. Epub 2019 Sep 30. PMID: 31767182; PMCID: PMC6812410.
  3. Wang JY, Wang QW, Yang XY, Yang W, Li DR, Jin JY, Zhang HC, Zhang XF. GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach. Front Endocrinol (Lausanne). 2023 Feb 1;14:1085799. doi: 10.3389/fendo.2023.1085799. PMID: 36843578; PMCID: PMC9945324.
  4. Honigberg MC, Chang LS, McGuire DK, Plutzky J, Aroda VR, Vaduganathan M. Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review. JAMA Cardiol. 2020 Oct 1;5(10):1182-1190. doi: 10.1001/jamacardio.2020.1966. PMID: 32584928; PMCID: PMC7744318.
  5. Pesta DH, Samuel VT. A high-protein diet for reducing body fat: mechanisms and possible caveats. Nutr Metab (Lond). 2014 Nov 19;11(1):53. doi: 10.1186/1743-7075-11-53. PMID: 25489333; PMCID: PMC4258944.
  6. Wang X, Liu H, Chen J, Li Y, Qu S. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1. Int J Endocrinol. 2015;2015:651757. doi: 10.1155/2015/651757. Epub 2015 Aug 20. PMID: 26366173; PMCID: PMC4558455.
  7. Janus C, Vistisen D, Amadid H, Witte DR, Lauritzen T, Brage S, Bjerregaard AL, Hansen T, Holst JJ, Jørgensen ME, Pedersen O, Færch K, Torekov SS. Habitual physical activity is associated with lower fasting and greater glucose-induced GLP-1 response in men. Endocr Connect. 2019 Dec;8(12):1607-1617. doi: 10.1530/EC-19-0408. PMID: 31804964; PMCID: PMC6933827.
  8. Lim J, Henry CJ, Haldar S. Vinegar as a functional ingredient to improve postprandial glycemic control-human intervention findings and molecular mechanisms. Mol Nutr Food Res. 2016 Aug;60(8):1837-49. doi: 10.1002/mnfr.201600121. Epub 2016 Jun 27. PMID: 27213723.
  9. Xue C, Li G, Gu X, Su Y, Zheng Q, Yuan X, Bao Z, Lu J, Li L. Health and Disease: Akkermansia muciniphila, the Shining Star of the Gut Flora. Research (Wash D C). 2023;6:0107. doi: 10.34133/research.0107. Epub 2023 Apr 3. PMID: 37040299; PMCID: PMC10079265.
  10. Abid R, Waseem H, Ali J, Ghazanfar S, Muhammad Ali G, Elasbali AM, Alharethi SH. Probiotic Yeast Saccharomyces: Back to Nature to Improve Human Health. J Fungi (Basel). 2022 Apr 24;8(5):444. doi: 10.3390/jof8050444. PMID: 35628700; PMCID: PMC9147304.
  11. Jung EY, Lee JW, Hong YH, Chang UJ, Suh HJ. Low Dose Yeast Hydrolysate in Treatment of Obesity and Weight Loss. Prev Nutr Food Sci. 2017 Mar;22(1):45-49. doi: 10.3746/pnf.2017.22.1.45. Epub 2017 Mar 31. PMID: 28401087; PMCID: PMC5383141.
Blood GlucoseUnderstanding GLP-1 Agonists in Weight Loss and Health