Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of drugs widely prescribed by physicians to control blood sugar in the treatment of type 2 diabetes and are nowbeing highly acclaimed for their advantages in weight management as well. GLP-1RAs mimic the physiological effects of the glucagon-like peptide-1 (GLP-1) hormone, which is among a large group of satiety hormones naturally produced by the body and released into the intestines in response to food intake. GLP-1 signals the release of insulin by the pancreas for glucose uptake from the blood; it slows the transit of food through the stomach inducing fullness and satiety; and it mediates nutrient absorption, breakdown, and utilization.

Studies on GLP-1RAs have shown they induce a slew of other favorable biological effects as well, such as reduced inflammation, improved heart function, reduced body fat storage, and improved hypothalamic regulation of body weight and energy (calorie) expenditure. Altogether GLP-1RA therapy leads to weight loss by way of appetite control and reduced food intake, and also by way of efficient sugar, fat, and energy metabolism. However, it is critical for GLP-1RA drugs, such as semaglutide and tirzepatide, to be used in conjunction with improved diet and exercise to better guarantee results and a healthier body long term.

Specific foods and eating behaviors boost the secretion and effects of GLP-1 naturally, and may, therefore, safely enhance the effects of GLP-1RA therapy. The production of gut peptides is greatly influenced by the integrity of the gut microbiota. Food that cultivates a strong microbiota, like fermentable carbohydrates, dietary fiber, and probiotics have been found to increase secretion of GLP-1 into the gut. Tea, curcumin, cinnamon, wheat, soybean, and resveratrol have also been found to promote GLP-1 release into the gut. Furthermore, the timing of food intake throughout the course of a day has profound effects on digestion and satiety hormones, with daytime eating being significantly favorable for GLP-1 production and action. Aside from diet being a fundamental means of achieving health, good nutrition can work in tandem with GLP-1RA therapy to reach weight and health goals more efficiently and rapidly.

Nutrition and dietary behaviors can also mitigate or prevent common side effects of GLP-1RA therapy. Short-term side effects are predominantly gastrointestinal, with patients frequently experiencing nausea, vomiting, and diarrhea. A registered dietitian can help patients eat in specific ways that alleviate such gastrointestinal symptoms, in addition to monitoring the onset of more severe symptoms. Those utilizing the medications at higher doses or for longer duration, specifically for weight loss, tend to be at greater risk of more severe side effects, such as acute cholecystitis (inflammation of the gallbladder) and pancreatitis (inflammation of the pancreas).

Although GLP1-RA are acclaimed for their reduced tendency to induce hypoglycemia, it is always a risk to be considered with diabetic medications. Adequate carbohydrate, fat, and protein intake remains critical to maintain blood nutrient levels and avoid deficiencies. Medical nutrition therapy protocols can reduce the risk of mild or severe side effects; and with the help of a registered dietitian, this can be done according to the patient's personal condition and needs.

Exercising while on GLP-1RA therapy is also critical to enhance health outcomes both short-term and long-term. One study found that GLP-1RA together with habitual physical activity enhanced pancreatic insulin function more so than GLP-1RA alone, making it easier to manage blood sugar and quicker to lose weight. Weight loss often comes with muscle mass loss as the body taps into fat and protein reserves in a setting of caloric restriction. Muscle loss can lead to a reduced resting metabolic rate and, in turn, an increased risk for future weight regain.

Appropriate exercise type and frequency can slow or prevent the decrease in muscle mass during weight loss and, instead, maintain, or even build, muscle strength and one’s resting metabolic rate. In addition to making GLP-1RA therapy more effective, exercise helps one reap the benefits of weight loss without the metabolic costs that may come with it, making it easier to achieve and maintain goals long-term.

Adopting appropriate nutrition and exercise habits would allow one to eventually wean off of a GLP-1RA with significantly lower risks of rebounding to previous unfavorable weight and health status. It is preferable to avoid drug dependency and the unknowns that come with it. Pumping the body with one hormone for too long may throw off the metabolic harmony innately desired for smooth physiological function. Patients who require GLP1-RA therapy to achieve specific metabolic and weight goals must adopt nutrition and exercise practices in order to eventually, and more quickly, discontinue use and still be able to maintain the numbers they have achieved.

It is proven that good nutrition coupled with habitual physical activity is the most effective means of achieving optimal all-around health of the body (and mind) without any adverse effects when done safely. Just as importantly, nutrition and exercise education and practice give a patient autonomy over his or her own health, which itself is empowering, motivating, and promising to the individual—not to mention, relieving to the medical professional and overall health system. Nutrition and exercise lifestyle improvements while on GLP-1RA therapy will not only enhance the beneficial effects of the GLP-1RAs, it will also set patients up for health success long-term.

References
[1] Zhao X, Wang M, Wen Z, Lu Z, Cui L, Fu C, Xue H, Liu Y, Zhang Y. GLP-1 Receptor Agonists: Beyond Their PancreaticEffects. Front Endocrinol (Lausanne). 2021 Aug 23;12:721135. doi: 10.3389/fendo.2021.721135.
[2] Dungan K, DeSantis A. Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus.UpToDate. 2023 Nov.
[3] Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014 Sep;15(3):181-7. doi:10.1007/s11154-014-9289-5.
[4] Yaribeygi H, Jamialahmadi T, Moallem SA, Sahebkar A. Boosting GLP-1 by Natural Products. Adv Exp Med Biol.2021;1328:513-522. doi: 10.1007/978-3-030-73234-9_36.
[5] Covasa M, Stephens RW, Toderean R, Cobuz C. Intestinal Sensing by Gut Microbiota: Targeting Gut Peptides. Front Endocrinol (Lausanne). 2019 Feb 19;10:82. doi: 10.3389/fendo.2019.00082.
[6] Janus C et al. Habitual physical activity is associated with lower fasting and greater glucose-induced GLP-1response in men. Endocrine Connections. 2019 Dec; 8:12, 1607-1617. doi.org/10.1530/EC-19-0408
[7] Weiss EP, Jordan RC, Frese EM, Albert SG, Villareal DT. Effects of Weight Loss on Lean Mass, Strength, Bone, and Aerobic Capacity. Med Sci Sports Exerc. 2017 Jan;49(1):206-217. doi: 10.1249/MSS.0000000000001074.

About the Author
Marissa Zarco Hoffman is the founder of her private practice, Marissa Zarco Nutrition, where she provides personalized nutrition therapy for a wide range of needs, including weight management, athletic performance, pre- and post-natal nutrition, and medical conditions. She also conducts seminars for businesses and volunteers in the community to educate youth. Marissa holds a Master of Science in Nutrition and Exercise Physiology from Columbia University
and a Bachelor of Science in Biological Anthropology and Anatomy from Duke University. You can visit her online at www.marissazarconutrition.com or on Instagram (@MarissaZarcoNutrition).

Disclaimer: The content contained in this article has been written by Marissa Zarco Hoffman, MS, RD, LD/N of Marissa Zarco Nutrition, LLC in good faith, but is not intended to be a substitute for advice, diagnosis or treatment by a qualified medical professional. Marissa Zarco Hoffman, MS, RD, LD/N is not held liable for the use of and reliance on the opinions, estimates, forecasts and findings in this document.