BY Samuel Mathis, MD, Assistant Professor, UTMB, Family Medicine, UTMB
In the past few months, I have seen several patients with what one of my colleagues calls a “GLP-1 deficiency.” Where I work, semaglutide has quickly become the newest fad diet. It does not help that the media and pharmaceutical companies continue to promote these drugs as “cures” rather than weight loss aids. I admit, many patients are seeing significant results in their weight while on this medication class. Some patients are even willing to stay on the medication despite the numerous negative side effects. Glucagon-like peptide-1 (GLP-1) receptor agonists work by increasing the production of insulin to maintain blood glucose levels, delay gastric emptying, slowing intestinal transit, and reducing appetite (and by extension total consumption of calories). These medications were initially utilized for patients with diabetes, but Wegovy has recently gained FDA approval for weight loss. GLP-1 receptor agonists improve insulin and glucagon levels and work to promote weight loss by adjusting the age-old calculation of weight loss “Calories-in vs calories-out.” However, the significant weight loss achieved through these medications is not permanent without significant lifestyle changes.
The research has shown significant improvement in weight while on these medications, but the concern comes once patients reach their desired weight loss goal. A recent multi-country study (Wilding 2022) out of Canada, Germany, UK, US, and Japan found that on average, patients regained two-third of their prior weight loss within 1 year after discontinuation of semaglutide. After stopping semaglutide, participants regained 11.6% of the 17.3% body weight lost over the year following medication cessation. One limitation was that this study did not look at if participants were involved in any lifestyle interventions that may impact weight. The study found that not only did weight return, but also other benefits noted during the study (blood pressure, A1c levels, CRP levels) also began to worsen back to pre-study levels.
The interesting aspect of this study is the lack of lifestyle interventions that took place in the original STEP-1 trial. Another study (Rubino 2021) compared semaglutide maintenance dose vs placebo after 20 weeks of escalation to 2.4mg/weekly with continued lifestyle interventions that were included throughout the trial. The groups were monitored for 48 weeks. These lifestyle interventions were counseling regarding a reduced-calorie diet (500-kcal/d deficit) and recommendations for 150 min/wk of physical activity. In this trial, participants on the placebo gained on average 6.9% of their body weight back whereas those on semaglutide lost an additional 7.9% of their body weight.
Both studies highlight that weight loss through GLP-1 receptor agonists requires continued medication use to maintain the desired weight. There is limited research on the dietary changes among GLP-1 users during or after treatment. Studies (Singh 2022) have found that when paired with lifestyle intervention, there is a significant boost to weight loss compared to a placebo. While on these medications, patients must receive education on proper lifestyle changes in diet and exercise. We should encourage patients to work on adjusting their diet entirely to best impact their weight loss. Low-processed diets with high intake of plants are vital to health. Additionally, patients should use time on GLP-1 receptor agonists to relearn the appropriate amount of food they should each at each meal.
When discussing an appropriate diet, I utilize Michael Pollan’s three rules for eating. Rule 1: Eat (real) food. This means eating foods that our ancestors would have recognized. Rule 2: Not too much. This is most Americans’ problem. We eat too much food. I constantly work to help patients identify appropriate portion sizes. Finally, rule 3: Mostly plants. I am not saying to not eat meat. I just mean that most of our diet should be plant-based. That’s it. Simple rules, but incredibly difficult to follow.
The importance of these studies highlights the fact that medications such as semaglutide are meant to be used as tools to assist a patient’s relation to food rather than a means to an end. In my practice, I have worked with patients who complain that they feel full after eating 2-3 bites of a cake. Imagine their surprise when I begin to talk about the appropriateness of eating cake at all. It is only through proper education on effective lifestyle changes will patients see lasting results in their health and weight. GLP-1 receptor agonists can be a wonderful tool to help patients with obesity, but sustained results will only be achieved when paired with appropriate education on healthy diet, exercise, and lifestyle changes that are shown to improve overall health and well-being.
References
Wilding JPH, et.al; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725.
Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414–1425. doi:10.1001/jama.2021.3224
Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27. PMID: 34706925; PMCID: PMC8717485.
Pollan, M., & Kalman, M. (2011). Food rules: an eater’s manual. New York, Penguin Press.