Peptides for Weight Loss GLP-1 Antagonists

Peptides for Weight Loss: GLP-1 Antagonists

For most of history, humans have consumed fresh, seasonal produce and hormone-free meats. The industrial revolution’s effect on modern farming practices had a tremendously detrimental effect on our food production and as a result, “for about the last 100 years, synthetic chemicals, refined foods, sugar, and salt have replaced many of the natural foods our ancestors ate” (Micozzi, 2015). The current Standard American Diet (SAD) includes “high-fat and cholesterol, high-protein, high-sugar, and excess salt intake, as well as frequent consumption of processed and ‘fast foods’ [and] promote[s] obesity, metabolic syndrome, and cardiovascular disease” (Manzel et al., 2014). The Standard American Diet that most Americans consume is deficient in many ways and not only leads to obesity, but provides such a limited scope of nutrients. So instead of having the diverse and plentiful bacterial colonies we should have in our gut, we only have a few and they tend to be homogenous. Having an ecologically diverse microbiome in the gut “both in terms of richness (number of taxa present) and evenness (abundance of many microbial constituents) … has been generally associated with health [while] conversely, a relative lack of diversity is apparent in the gut microbiome in diseases ranging from obesity to inflammatory bowel disease and types 1 and 2 diabetes; and in the skin microbiome in atopic dermatitis and psoriasis” (Lloyd-Price et al., 2016). The microbiome not only affects our physical health, but our mental health as well: “nutrients provide the biological building blocks for brain chemicals called neurotransmitters, which affect how we think and feel…[and] when you don’t eat enough high-quality neuronutrients- literally “brain nutrients”- your body cannot make adequate amount of mood-enhancing neurotransmitter” (Challem, 2007). The effect of diet on the brain can also be seen in mood, as “95 percent of the body’s serotonin is made in the gut” (Northrup, 2010). It is not only foods that one should be cognizant of, but also the amount of sugar we consume: “In the United States 100 years ago, we consumed 3 lb of sugar per person per year; we now consume 180 lb” (Micozzi, 2015). Dr. Mark Hyman (2016) encourages us to be aware of “the ‘white menace’– white sugar, white flour, and white fat (shortening).” Yikes!

It is no wonder then, that more and more Americans are being classified as obese. Technically, obesity is defined as having a body mass index (BMI) greater than or equal to 30, when weight is divided by height and if your BMI is 25 to 29, it falls within the overweight range. While there are other ways to measure obesity, including waist to hip ratio, “the National Institutes of Health and the World Health Organization have both adopted BMI as a criterion for defining obesity [since] this made interpretation simpler, eliminated the need for sex-specific height/weight tables, and provided a measurement that is better correlated with other estimates of adiposity”(Bray et al., 2018). As a result, it has become the standard for research. Obesity has quickly become one of the largest epidemics in America, and has subsequently spread throughout the world as other countries adopt the Standard American Diet. While this diet “has long been implicated in contributing to the health challenges experienced in the United States” (Grotto & Zied, 2010), it is now responsible for the decrease in health indicators globally (Ranganathan. & Vennard, 2016).  According to the most recent US data by the CDC, the “percent of adults aged 20 and over who are overweight, including obesity: 73.6% the US obesity prevalence was 41.9% as of 2020” (CDC, 2023). While the number of overweight individuals in American has remained constant in the last fifty years, the number of obese and extremely obese individuals has skyrocketed. This is highly concerning, since obesity is a primary cause of health problems including but not limited to “heart disease, stroke, type 2 diabetes and certain types of cancer that are some of the leading causes of preventable, premature death” (CDC, 2020).

While eating healthy is a cornerstone to weight loss, there are many factors which can make it hard to lose weight or keep it off including age, illness, injury or stress to name a few. A therapy that can be helpful in weight management is peptides, specifically GLP-1 (glucagon-like peptide-1) antagonists. These are also known as GLP-1 receptor blockers or GLP-1 inhibitors and are a type of medication specifically used to treat obesity.  GLP-1 antagonists are “currently one of the most promising biological systems for the development of effective obesity pharmacotherapies” (Kanoski, Hayes, & Skibicka, 2016). There are multiple mechanisms of action, which “highlight the complexity of the neural systems regulating energy balance, as well as the challenges for developing effective obesity pharmacotherapies” (Kanoski, Hayes, & Skibicka, 2016), but the main one is due to the fact that these agonists block the activity of the GLP-1 receptor, which is responsible for the effects of GLP-1 in the body (Seeds, 2020).

This is important because peptide GLP-1 is a hormone released by the intestines after we eat, and it plays a role in regulating glucose metabolism, appetite, and satiety as follows:

  1. Reduces appetite: By blocking the GLP-1 receptor, these medications can slow down gastric emptying, meaning that food stays in the stomach longer, leading to a prolonged feeling of fullness. This can result in a reduced caloric intake and ultimately weight loss.
  2. Decreases food cravings: They can modulate the reward pathway in the brain, which is responsible for food cravings and the pleasurable sensations associated with eating. By turning down these cravings, GLP-1 antagonists can make it easier for individuals to make healthier food choices and resist overeating.
  3. Improves glucose control: By blocking the GLP-1 receptor, these medications reduce glucose production by the liver and increase insulin secretion, leading to better blood sugar regulation. When blood sugar levels are more stable, it can help reduce cravings, especially for sugary and high-calorie foods, which contribute to weight loss.

In addition to the mechanisms of action listed above, endogenous GLP-1 made by our own body degrades quickly (about 2-3 minutes) which is why supplementing with peptides that help to continue this reaction work to reduce weight gain (Meier, 2012). Research has shown that “GLP-1 based treatment has been associated with weight loss and lower hypoglycemia risk” (Seeds, 2020).  They have been well studied in clinical trials such as the SCALE and STEP studies, and have even been approved by FDA for chronic weight management of obese or overweight adults (Wang 2023).  Overall, GLP-1 antagonists peptides are one way to help lose weight and maintain our health, especially since they are easy to administer, have no adverse reactions, and few to no side effects.


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About the author: Mary Genevieve Carty, MS, MHEd holds Masters degrees in Complementary and Integrative Health as well as Higher Education and is currently a doctoral student in Health Science at George Washington University’s College of Medicine and Health Science.  She is passionate about holistic health and wellness, and has additional training in teaching, Reiki, and Tapping/ Emotional Freedom Technique. Her research interests include resiliency, psychoneuroimmunology, neuroplastic pain, placebo/ nocebo effect, and bioenergy therapies.  The views she expresses are her own, and do not reflect any affiliation.

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Medically reviewed by Dr. Stephen Matta, DO, MBA CAQSM and Mary Anne Matta, MS, MA, LAC

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