by Benjamin Bikman, PhD
What happens after Ozempic?
Ozempic, a groundbreaking GLP-1 receptor agonist, has taken the medical world by storm as a highly effective tool for managing type 2 diabetes and achieving significant weight loss. For many, it’s been a game-changer, providing improved blood sugar control and meaningful progress toward weight loss goals.
However, what happens when someone stops taking Ozempic? It’s a question worth exploring, as discontinuation is common and carries its own set of challenges. The good news? There are strategies to sustain progress and maintain metabolic health even without the medication.
Why do people stop taking Ozempic?
While Ozempic is undoubtedly effective for weight loss, many people discontinue its use. In fact, real-world data indicates that up to 50% of patients stop taking GLP-1 receptor agonists like Ozempic within one year of initiating treatment, increasing to over 70% at year two.
The reasons for these high dropout rates vary, but include:
Cost and accessibility: Ozempic can be prohibitively expensive, and insurance coverage is not always comprehensive, leading many to discontinue treatment.
Perceived lack of progress: Over time, some individuals feel that the benefits—such as weight loss or improved blood sugar control—plateau, which can discourage continued use.
Lifestyle factors: Long-term adherence often requires pairing the medication with significant lifestyle changes, such as dietary adjustments and increased physical activity, which not all patients are prepared to maintain.
Mental health: The most famous effect of these drugs is to reduce cravings for unhealthy foods. In reality, this effect may be more widespread than initially appreciated, including reducing enjoyment of many things. This could explain the substantially elevated risk of depression and other mental health problems.
Side effects: Perhaps the most important reason some people drop the drugs is the gastrointestinal discomfort, including nausea and vomiting. Indeed, these complications become so unbearable that many often conclude that the benefits of weight loss (or maintained weight loss) aren’t worth the pain.
Understanding these barriers is key to finding alternative strategies that work and help sustain the progress achieved while on Ozempic.
The consequences of stopping Ozempic
When someone stops taking Ozempic, there are predictable metabolic and physiological consequences.
Let’s dive into what the science says:
Regaining weight
Weight regain is one of the most well-documented outcomes of discontinuing GLP-1 receptor agonists. A study published in The Lancet (Wilding et al., 2022) found that individuals who stopped taking semaglutide (the active ingredient in Ozempic) regained a significant portion of the weight they had lost, often within a year. This is likely due to the return of appetite and food cravings that were suppressed while on the medication.
Loss of fat-free mass
An important but less-discussed consequence is the impact on body composition. A pivotal study published in The New England Journal of Medicine (Heymsfield et al., 2021) revealed that roughly 40% of the weight loss achieved on GLP-1 receptor agonists comes from fat-free mass, including muscle and water. When weight is regained, it is often primarily fat, leading to an unfavorable shift in body composition and metabolic health.
Activation of PPAR-Gamma and fat cell dynamics
Interestingly, liraglutide—a similar GLP-1 receptor agonist—has been shown to activate PPAR-gamma, a nuclear receptor that regulates fat cell development. This activation may increase the number of fat cells, as demonstrated in a study published in Diabetes (Clemmensen et al., 2020). While this process can improve fat storage efficiency during weight loss, the increased number of fat cells persists even after stopping the medication, potentially making long-term weight maintenance more challenging.
Rebound in insulin resistance
Without the GLP-1 receptor activation provided by Ozempic, blood sugar control can deteriorate, and insulin resistance may return. This can exacerbate metabolic issues, including the risk of type 2 diabetes progression.
The good news: A path forward without Ozempic
While there are undeniable challenges to stopping Ozempic, there is also hope. Several evidence-backed strategies can help maintain progress and support metabolic health.
1. Control carbohydrates
One of the most effective ways to keep insulin levels low is to control carbohydrate intake. High-carb diets can lead to spikes in blood sugar and insulin, perpetuating insulin resistance and fat storage. Instead, focus on nutrient-dense, lower-carb foods such as:
Leafy greens and non-starchy vegetables
Healthy fats like avocado and olive oil
High-quality proteins like eggs and fish
By reducing the carbohydrate load, you can better manage blood sugar and maintain a favorable metabolic state.
In a study conducted by Hengist et al. (2024), participants consuming a low-carbohydrate (LC) meal showed significantly higher postprandial GLP-1 levels compared to those consuming a low-fat (LF) meal. Specifically, the active GLP-1 concentrations after the LC meal were more than double those following the LF meal (6.44 pg/mL vs. 2.46 pg/mL, p < 0.0001).
This difference highlights the potential for low-carbohydrate meals to stimulate greater secretion of GLP-1, a gut-derived hormone known for its role in promoting satiety and regulating blood sugar levels. These findings suggest that incorporating low-carbohydrate dietary strategies may naturally enhance GLP-1 levels, thereby supporting metabolic health and appetite regulation even without pharmacological intervention
2. Incorporate GLP-1-stimulating foods and products
Natural interventions that stimulate GLP-1 secretion can be highly effective in maintaining metabolic health. Two standout options are yerba mate and dietary fiber, both of which work through specific mechanisms to enhance GLP-1 activity.
Yerba mate: A natural GLP-1 booster
Yerba mate, a traditional South American herbal tea, has demonstrated remarkable effects on GLP-1 stimulation. Its benefits extend beyond GLP-1 secretion to also enhance the hormone’s lifespan in the body. This dual effect makes yerba mate particularly powerful.
Stimulating GLP-1 production: Yerba mate contains bioactive molecules, such as chlorogenic acids and saponins, which directly activate intestinal L-cells to produce more GLP-1. Chlorogenic acids, specifically, have been shown to enhance the responsiveness of L-cells to food stimuli, effectively boosting the natural secretion of GLP-1 after a meal.
Prolonging GLP-1 action: Yerba mate’s high ferulic acid content inhibits dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for breaking down GLP-1. By reducing DPP-4 activity, ferulic acid allows GLP-1 to remain active in the bloodstream for a longer duration, thereby amplifying its effects on satiety and blood sugar regulation.
Reducing inflammation: Chronic inflammation can impair GLP-1 signaling and insulin sensitivity. Yerba mate’s rich antioxidant profile—including polyphenols—helps reduce oxidative stress and inflammation, creating a more favorable environment for GLP-1 activity.
These mechanisms make yerba mate an ideal natural alternative or complement to GLP-1 receptor agonist medications. Incorporating yerba mate into a daily routine—whether as a tea or a supplement—can support appetite control, metabolic health, and sustained energy levels.
Dietary fiber: The foundation of GLP-1 stimulation
Dietary fiber plays a pivotal role in enhancing GLP-1 activity through its fermentation by gut bacteria. This fermentation process produces short-chain fatty acids (SCFAs), which directly stimulate GLP-1 secretion from intestinal L-cells. Fiber also slows gastric emptying, ensuring a more gradual release of glucose into the bloodstream and reducing the likelihood of insulin spikes.
Importantly, fiber-rich diets support a healthy gut microbiome, which is increasingly recognized as a critical regulator of GLP-1 production and overall metabolic health.
A fiber supplement designed to optimize GLP-1 secretion can provide a convenient and effective way to ensure consistent intake. Unlike whole foods, targeted fiber products can deliver precise doses of fermentable fibers to maximize SCFA production and GLP-1 stimulation.
Together, yerba mate and a high-quality fiber supplement create a synergistic approach to maintaining GLP-1 levels, promoting satiety, and supporting sustainable metabolic health—even in the absence of medications like Ozempic.
Conclusion: Empowering long-term success
While Ozempic is a powerful tool, it’s not the only path to better health and one many people find themselves increasingly stepping away from. The challenges of stopping the medication are real, but they also present an opportunity to adopt sustainable habits that support lasting metabolic health. By controlling carbohydrate intake, incorporating GLP-1-stimulating supplements, and prioritizing a healthy lifestyle, you can take control of your health journey.
About the author: Dr. Benjamin Bikman is the director of the Unicity Scientific Advisory Board. He earned his doctorate in bio-energetics and specialized metabolic disorders as a postdoctoral fellow of the Duke-National University of Singapore. As a professor and scientist at Brigham Young University, Dr. Bikman’s focus is understanding chronic, modern-day diseases with an emphasis on the origins and consequences of metabolic disorders, including diabetes and obesity. He frequently publishes his research in peer-reviewed journals and presents at international science meetings.
References
Weiss, T. et al. (2020). Real-world adherence and discontinuation of glucagon-like peptide-I receptor agonists therapy in type 2 diabetes mellitus patients in the United States. Patient Preference and Adherence, 14:2337-2345.
Wilding, J. P. H., et al. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity & Metabolism, 24(8):1553–1564.
Hengist, A., et al. (2024). Gut-derived appetite hormones do not explain energy intake differences in humans following low-carbohydrate versus low-fat diets. Obesity (Silver Spring), 32(9):1689–1698.
An Y., et al. (2024). Ferulic acid reduces GLP-1 degradation to ameliorate diet-induced obesity-associated hepatic steatosis. Food Frontiers, 5(2):691-707.
Chen, J., et al. (2017). GLP-1/GLP-1R signaling in regulation of adipocyte differentiation and lipogenesis. Cellular Physiology and Biochemistry 42:1165-1176.
Yanagimoto, A., et al. (2023). Acute dose-response effectiveness of combined catechins and chlorogenic acids on postprandial glycemic responses in healthy men: Results from two randomized studies. Nutrients 15(3):777.
Psichas, A., et al. (2014). The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. International Journal of Obesity 39:424-429.
Kornelius, E., (2024). The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy. Scientific Reports 14:24433.
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