GLP-1 Background and Role
Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced and secreted by enteroendocrine L-cells within the small intestine, primarily in response to the ingestion of nutrients such as proteins, carbohydrates, or fats. It plays an essential role in maintaining glucose homeostasis through the incretin effect. This effect involves stimulating insulin secretion in a glucose-dependent manner, suppressing glucagon, and delaying gastric emptying, which leads to reduced appetite and feelings of fullness. Glucagon is a hormone that increases blood glucose levels in response to low blood glucose, heightened sympathetic nervous system activity (e.g., during stress, such as fasting or exercise), and elevated circulating amino acids.
Beyond its effects on pancreatic hormone regulation, the GLP-1 hormone also slows gastric emptying and promotes feelings of fullness and satiety through direct signaling to the central nervous system. Additionally, it has been shown to restore pancreatic β-cell mass and insulin sensitivity, a key factor in the long-term management of glycemic control.
Endogenous GLP-1 versus GLP-1 Receptor Agonists
While endogenous GLP-1 hormones are secreted after meals and act transiently to promote insulin secretion, suppress glucagon, and promote satiety in a balanced physiologic fashion, GLP-1 receptor agonists (GLP-1 RAs) provide prolonged receptor engagement.
GLP-1 RAs are pharmacological agents designed to mimic the activity of endogenous GLP-1 and resist its enzymatic breakdown. Unlike endogenous GLP-1 hormones, which fluctuate throughout the day, GLP-1 RAs deliver a supraphysiological dose. An increased half-life, ranging from several hours to multiple days, allows for sustained activation of the GLP-1 receptors (GLP-1Rs) throughout the body. In turn, sustained GLP-1 activity may lead to a more robust glycemic control and appetite suppression, but a greater incidence of side effects, such as GI discomfort, for some individuals.
By comparison, endogenous GLP-1 hormones are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4), which limits their half-life to approximately one to two minutes. Despite this brief activity, GLP-1 exerts its effects by binding to GLP-1Rs distributed throughout various tissues, including pancreatic β-cells, the gastrointestinal (GI) tract, the heart, and areas of the brain involved in appetite regulation. This widespread receptor expression highlights the hormone’s integrative role in metabolic regulation, cardiovascular function, and neuroendocrine signaling.
Common Complaints with GLP-1 RAs
Despite their clinical effectiveness in improving glycemic control and supporting weight maintenance, GLP-1 RAs are commonly associated with a range of side effects. During the initial stages of use, GLP-1 RAs may cause nausea, vomiting, diarrhea, constipation, and bloating. These GI symptoms are often a result of delayed gastric emptying and central satiety signaling.
In addition to digestive discomfort, reduced appetite and caloric intake may lead to unintended nutritional deficiencies over time. A decreased intake of key nutrients, such as dietary protein, healthy fats, vitamin B12, and magnesium (Mg), is of particular concern, especially in individuals with pre-existing marginal nutrient status or restricted diets.
Furthermore, the combination of reduced energy intake and suboptimal protein consumption may contribute to a reduction in skeletal muscle mass and fat-free mass, especially in adults of advanced age or those not engaging in regular resistance training. In an effort to reduce sarcopenia risk, nutritional and lifestyle strategies should be at the forefront when using GLP-1 RA support.
Nutritional and Lifestyle Strategies for GLP-1 Support
Nutritional and lifestyle strategies can significantly support both endogenous GLP-1 activity and the effectiveness of GLP-1 RA use. Promoting GI health and balanced detoxification mechanisms, ensuring nutrient sufficiency, and maintaining muscle mass are crucial for individuals aiming for healthy glucose and insulin metabolism, as well as balanced hormone levels. A foundational dietary approach incorporates a fiber and antioxidant-rich diet, with the inclusion of pre- and probiotic-rich foods, while also prioritizing sufficient lean protein consumption and healthy fats.
Supplementation may provide additional targeted support to complement the body's natural GLP-1 functions and aid those looking to support their metabolic health.
Ultimately, GLP-1 hormones represent a critical component in metabolic health. Leveraging dietary, supplemental, and lifestyle interventions, with fiber-rich nutrition, microbiome support, nutrient repletion, and resistance training, may promote a healthy metabolic state. Integrating these strategies may support sustainable weight management, improved glucose metabolism, and overall metabolic health.
To learn more about dietary, botanical, and lifestyle interventions in metabolic health:
4 Surprising Botanicals to Promote Normal GLP-1 Production
Muscle Tone Matters: The Key to Optimal Body Composition and Metabolic Health
Role of Omega-3 on Muscle Health and Function
By Rachel B. Johnson, MS, CNS, LDN