GLP-1 Agonists: What are They? And are they worth it?
By Faith Haney, PostGlo Student Intern
There’s a good chance you’ve heard of Ozempic or other medications like Wegovy and Mounjaro that have been touted as the latest solution to quick weight loss. These medications, known as GLP-1 agonists, have permeated both the medical field and social media as powerful tools to combat obesity* or allow celebrities and influencers to get closer to the current trending beauty standard. You may have even been recommended or prescribed one of these drugs by your health care provider. Clearly, these medications are a big deal, but what exactly are they? What role does nutrition play when taking these medications? And, most importantly, should we be worried about the potential dangers that may be lurking in the shadows of their supposed benefits?
*I use obesity in this context to refer to the medical definition of a body mass index (BMI) ≥ 30 kg/m2, though it is important to note that the BMI scale is a contested form of measurement.
What are GLP-1 agonists?
GLP-1 (glucagon-like peptide-1) agonists are a type of medication that has typically been used to regulate blood sugar levels in those with type 2 diabetes. They mimic glucagon-like peptide-1, a hormone from the small intestine that works to lower blood sugar levels by initiating insulin release from the pancreas after eating. Additionally, GLP-1 and GLP-1 agonists slow down digestion and reduce appetite. Recent research demonstrates that appetite suppression from the use of GLP-1 agonists can lower calorie intake by 35%, which in turn leads to weight loss (Friedrichsen et al., 2021). Injections of the GLP-1 agonist semaglutide, the active ingredient in Ozempic and Wegovy, have been shown to result in around 15% loss of body weight over 12 months (Rodriguez & Khalsa, 2024; Wadden et al., 2021). Likewise, tirzepatide, the GLP-1 agonist in Mounjaro, yields 15-25% body weight loss in clinical trials (Azuri et al., 2023). In light of these results, the use of GLP-1 agonists has skyrocketed in recent years. However, these potent drugs are not suitable for just anyone looking to lose weight.
Who should take GLP-1 agonist medications?
First and foremost, you should not take these medications unless they have been prescribed by a trusted healthcare professional. GLP-1 agonists are primarily used to treat type 2 diabetes and obesity. The former condition benefits from the blood sugar-lowering effects of the drug and is generally recommended if other medications like metformin have proven to be ineffective in lowering A1C (Cleveland Clinic, 2023). In contrast, obesity is a complex condition that may or may not require medication to treat. Therefore, use of GLP-1 agonists for this population should be carefully evaluated by health professionals and considered along with other health markers to determine whether the benefits outweigh the risks. It is important to note that in either case, GLP-1 agonists should be viewed as a supplement to (not a replacement for) dietary and lifestyle changes for the most effective management of the condition.
What are the nutritional considerations when taking GLP-1 agonists?
While taking these weight loss drugs, maintaining proper nutrition and exercise habits is key to ensuring metabolic health in the long-term. When losing weight, be aware of potential loss of muscle mass. Having adequate muscle is essential for maintaining metabolism, joint and bone health, and preventing frailty and injury. Yet, studies have indicated that up to 39% of the rapid weight loss from GLP-1 agonists is lean muscle mass, indicating that adequate protein and resistance training are essential to minimize muscle loss (Prado et al., 2024).
When taking these drugs, consume at least 1 to 1.3 grams of protein per kilogram of body weight per day or aim to get at least 20-30% of your daily calories from protein (Wycherley et al., 2012). You probably don’t need to worry about tracking your protein intake every day and instead can easily meet your protein goals by consuming three balanced meals throughout the day with a protein source at each. Additionally, incorporate resistance training twice a week to help build strength and conserve muscle mass.
Because of the appetite-reducing effects of GLP-1 agonists, another concern is malnutrition. In some cases, these drugs may be too effective, resulting in weight loss at a rate beyond what is considered safe due to consuming an inadequate number of calories to sustain basic bodily functions (Richards & Khalsa, 2024). Not eating enough can also cause micronutrient deficiencies, particularly for vitamin B-12, calcium, iron, and vitamin D.
According to the American Society for Parenteral and Enteral Nutrition, you should consume at least 1400-1500 calories per day if a woman and 1500-1800 calories a day if a man while you are taking medically prescribed weight loss drugs (2024). Include nutrient-dense foods like fruits and vegetables, lean proteins, nuts and seeds, and whole grains at every meal to prevent malnutrition. Further, incorporate fiber-rich plant-based foods to support digestion, which can be negatively impacted by these medications.
What are the potential risks or side effects of GLP-1 agonists?
While GLP-1 agonists may seem like a miracle drug, a look into their possible side effects might change your mind. The most commonly reported side effect is gastrointestinal distress, including nausea, vomiting, diarrhea, constipation, and abdominal pain. More severe complications such as gastroparesis (stomach paralysis), bowel obstruction, gallstone attacks, and pancreatitis are less common but warrant seeking immediate medical attention (Shetty et al., 2022; Wharton et al., 2022).
In addition, the jury is still out as to whether GLP-1 agonists adversely impact mental health. Despite various reports of increases in anxiety and depression on these medications, the science has yet to determine whether they lead to worsening mental health (Tempia Valenta et al., 2024). Of particular concern is the impact of weight loss medication on those suffering from eating disorders or body dysmorphia. Alarms are being raised over the potential for abuse of these drugs by individuals having access or money to induce unnecessary and potentially dangerous weight loss without true medical need. The widespread use of weight loss medications by celebrities and social media influencers, especially those who were already considered thin to begin with, contributes to the added pressure to conform to unrealistic body ideals that can encourage unhealthy behaviors and poor self-esteem. Yet, even the perpetrators of these new standards are not immune to online scrutiny of their appearances, as the aesthetic changes caused by these drugs have begun to garner their own stigma. For example, the rapid weight loss from GLP-1 agonists is becoming associated with a social phenomenon known as “Ozempic face,” which is characterized by a hollowed out and sunken look to the face (Catanese, 2024).
Lastly, long-term use of GLP-1 agonists has been linked to an increased risk of developing thyroid cancer in some studies, so talk to your healthcare provider if you are already at a heightened risk of thyroid issues or cancer (Bezin et al., 2023). Remember, it is imperative to understand both the advantages and downsides of any medication before starting it so you can compare the risks and benefits to determine if it is right for you.
How effective are GLP-1 agonists in the long run?
While GLP-1 agonists may be a powerful tool to kickstart weight loss, they are certainly not a magic pill for permanent results unless you plan to stay on them (and suffer the side effects) for the rest of your life. Once you stop taking these medications, your appetite will again increase as your body fights to return to a higher weight as a compensation for the starvation it has endured. According to one study, participants regained around two-thirds of their GLP-1-induced weight loss within one year of stopping the medication (Wilding et al., 2022).
While GLP-1 agonists alone cannot ensure life-long weight loss, they can be used in conjunction with sustainable lifestyle practices that can support health in the long run, even after terminating use. There is no denying that GLP-1 agonists can play an important role for people facing immediate health problems in the short-term, but they are not a replacement for leading a healthy lifestyle. If you are currently taking or considering starting a GLP-1 agonist medication, ensure you reach out to a healthcare provider such as a registered dietitian who can help you nourish yourself properly and navigate health complications while on the drug.
References:
American Society for Parenteral and Enteral Nutrition. (2024). Malnutrition and Nutritional Deficiencies Associated with Weight Loss Therapies. https://www.nutritioncare.org/uploadedFiles/Documents/Malnutrition/Nutri-Considerations-for-Patients-on-Weight-Loss-Therapies.pdf
Azuri, J., Hammerman, A., Aboalhasan, E., Sluckis, B., & Arbel, R. (2023). Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. Diabetes, Obesity and Metabolism, 25(4), 961-964.
Bezin, J., Gouverneur, A., Pénichon, M., Mathieu, C., Garrel, R., Hillaire-Buys, D., ... & Faillie, J. L. (2023). GLP-1 receptor agonists and the risk of thyroid cancer. Diabetes care, 46(2), 384-390.
Catanese, L. (2024, February 5). GLP-1 diabetes and weight-loss drug side effects: Harvard Health. https://www.health.harvard.edu/staying-healthy/glp-1-diabetes-and-weight-loss-drug-side-effects-ozempic-face-and-more
Cleveland Clinic. (2023). GLP-1 Agonists. Cleveland Clinic. https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists
Friedrichsen, M., Breitschaft, A., Tadayon, S., Wizert, A., & Skovgaard, D. (2021). The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes, obesity & metabolism, 23(3), 754–762. https://doi.org/10.1111/dom.14280
Prado, C. M., Phillips, S. M., Gonzalez, M. C., & Heymsfield, S. B. (2024). Muscle matters: the effects of medically induced weight loss on skeletal muscle. The Lancet Diabetes & Endocrinology, 12(11), 785-787.
Richards, J. R., & Khalsa, S. S. (2024). Highway to the danger zone? A cautionary account that GLP‐1 receptor agonists may be too effective for unmonitored weight loss. Obesity Reviews, 25(5), e13709.
Rodriguez, P. J., Cartwright, B. M. G., Gratzl, S., Brar, R., Baker, C., Gluckman, T. J., & Stucky, N. L. (2024). Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity. JAMA internal medicine, 184(9), 1056-1064.
Shetty, R., Basheer, F. T., Poojari, P. G., Thunga, G., Chandran, V. P., & Acharya, L. D. (2022). Adverse drug reactions of GLP-1 agonists: a systematic review of case reports. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 16(3), 102427.
Tempia Valenta, S., Nicastri, A., Perazza, F., Marcolini, F., Beghelli, V., Atti, A. R., & Petroni, M. L. (2024). The impact of GLP-1 receptor agonists (GLP-1 RAs) on mental health: a systematic review. Current Treatment Options in Psychiatry, 11(4), 310-357.
Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O'Neil, P. M., Rubino, D. M., Skovgaard, D., Wallenstein, S. O. R., Garvey, W. T., & STEP 3 Investigators (2021). Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA, 325(14), 1403–1413. https://doi.org/10.1001/jama.2021.1831
Wharton, S., Davies, M., Dicker, D., Lingvay, I., Mosenzon, O., Rubino, D. M., & Pedersen, S. D. (2022). Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice. Postgraduate medicine, 134(1), 14-19.
Wilding, J. P., Batterham, R. L., Davies, M., Van Gaal, L. F., Kandler, K., Konakli, K., ... & STEP 1 Study Group. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism, 24(8), 1553-1564.
Wycherley, T. P., Moran, L. J., Clifton, P. M., Noakes, M., & Brinkworth, G. D. (2012). Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. The American journal of clinical nutrition, 96(6), 1281–1298. https://doi.org/10.3945/ajcn.112.044321