Obesity is an epidemic currently facing the United States, with over 40% of the adult population struggling with this disease [1]. Long-term weight control and management is approached by three approaches: lifestyle changes, medications, and surgery. Lifestyle changes involve changes in the individual’s diet and exercise routine but have a high rate of regaining weight. Surgical interventions involving changing the size of the stomach and small intestine to reduce ingested food volume. While this treatment results in weight loss, the body is irreversibly changed. Medications have been available for decades with variable effects on weight loss and long-term use [2]. Recently, a newer class of medication known as glucagon-like peptide-1 receptor agonists (GLP-1 RA) are gaining popularity due to very promising results for weight loss and reduction of other disease processes.
GLP-1 RA were initially developed in the 2000’s as a treatment for type-2 diabetes. Significant weight loss was consistently noted as an additional effect. These effects occurred due to GLP-1 RA mimicking the hormone GLP-1. This hormone functions by stimulating insulin release from the pancreas, decreasing the release of glucagon from the pancreas, and slowing the rate at which the stomach empties [3]. These effects to the primary blood glucose-controlling hormones make this class of medication an ideal candidate for type 2 diabetes control as well as weight loss due to decreased food intake. Additionally, GLP-1 receptor agonists have been shown to have more global effects, including neuroprotection, improved heart contractility and blood flow, and increased energy expenditure via the hypothalamus. While the primary reason for weight loss with GLP-1 receptor agonists is up for debate, increased satiety along with these combined effects lead to an increased level of satiety. When used regularly, individuals medicated with GLP-1 RA lost approximately 15 lbs. compared to a placebo [4].
GLP-1 RA are primarily administered by injection. This is due to the current medications having poor oral bioavailability. One exception is the medication Rybelsus, an oral form of semaglutide, that is formulated to have increased drug uptake in the stomach [5]. Analogs of the human GLP-1 are used due to a very short half-life of the hormone due to degradation. This is avoided in the current drugs by modification of the amino acid sequence to increase longevity.
Side-effects of the medication have been frequently described [3]. More common effects include gastrointestinal distress including nausea, diarrhea, and upset stomach. GLP-1 RA are also not recommended in those with a history of certain types of endocrine tumors. While no history of these conditions has been described in humans, cancer prevalence has been documented in rodent models. Patients using GLP-1 RA also need to monitor for pancreatitis. While no definitive relationship has been connected between the two, those using these medications have developed severe cases of pancreatitis while on these medications. Cosmetic issues have also been documented. Rapid and profound weight loss causes thin and drooping faces with consistent usage, commonly known as “Ozempic face” [6]. Overdoses of GLP-1 RA are rarely documented and most commonly involve frequent vomiting episodes, nausea, and minimal changes in blood glucose levels [7].
Drawbacks to these medications include intolerance of the previously listed side-effects. Sourcing is another obstacle for finding medications. GLP-1 RA are labelled for control of type-2 diabetes and treatment of obesity along with diet and exercise. These medications have also been used for cosmetic weight loss due to their effectiveness and may be diverting supplies from populations requiring these for disease treatment.
GLP-1 RA are rapidly gaining attention and popularity for their rapid and significant weight loss. While originally being formulated as a treatment for type 2 diabetes, it has been labelled as a treatment for obesity when paired with diet and exercise. These medications may be labelled for neurologic or cardiac disease in the future as more evidence with different diseases is found. Currently, GLP-1 RA are becoming a game changing tool for practitioners treating chronic illness and for those affected by them.
References:
1. U.S. Department of Health and Human Services. (2021, September). Overweight & Obesity Statistics - Niddk. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity#:~:text=%25)%20are%20overweight.-,More%20than%202%20in%205%20adults%20(42.4%25)%20have%20obesity,who%20are%20overweight%20(27.5%25).
2. Jeong D, Priefer R. Anti-obesity weight loss medications: Short-term and long-term use. Life Sciences. July 21, 2022. Accessed November 14, 2023. https://www.sciencedirect.com/science/article/abs/pii/S0024320522005252.
3. Collins L, Costello RA. Glucagon-like peptide-1 receptor agonists. National Library of Medicine. January 13, 2023. Accessed November 14, 2023. https://www.ncbi.nlm.nih.gov/books/NBK551568/.
4. Iqbal, J, Wu, H-X, Hu, N, et al. Effect of glucagon-like peptide-1 receptor agonists on body weight in adults with obesity without diabetes mellitus—a systematic review and meta-analysis of randomized control trials. Obesity Reviews. 2022; 23(6):e13435. doi:10.1111/obr.13435
5. 1. Hughes S, Neumiller JJ. Oral semaglutide. Clinical diabetes : a publication of the American Diabetes Association. January 2020. Accessed November 14, 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969659/.
6. Ewumi O. What is “Ozempic face” and how can people avoid it? Medical News Today. October 24, 2023. Accessed November 14, 2023. https://www.medicalnewstoday.com/articles/ozempic-face.
7. Elmehdawi RR, Elbarsha AM. An accidental liraglutide overdose: Case report. The Libyan journal of medicine. January 20, 2014. Accessed November 14, 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901387/.