The Rise of GLP-1 Agonists: Examining the Potential for Pharmaceutical Dependency

The recent expansion in the use of glucagon-like peptide-1 (GLP-1) receptor agonists, most notably semaglutide for weight management has generated considerable debate within clinical and public health domains. Originally developed for type 2 diabetes management, these agents have demonstrated significant efficacy in reducing body weight. However, their off-label use as primary weight-loss interventions raises important concerns regarding long-term safety, potential dependency, economic accessibility, and the broader implications of unregulated market alternatives. This review examines the pharmacological mechanisms underlying GLP-1 receptor agonists, discusses the financial and regulatory challenges associated with their use, and underscores the critical need for integrating sustainable lifestyle interventions. In doing so, it emphasizes the importance of ethical and policy frameworks to safeguard public health while ensuring that weight management strategies remain both effective and safe.

Mechanisms and Clinical Efficacy

GLP-1 receptor agonists function by replicating the function of incretin hormones, which help control appetite and glucose metabolism. Clinical trials have demonstrated their efficacy in promoting weight loss, with documented reductions in body mass observed throughout treatment durations (Wilding et al., 2022). Despite these benefits, the increasing reliance on these drugs as a primary intervention for weight loss, rather than as part of a comprehensive lifestyle modification plan, poses potentially serious risks.

A key concern is the uncertainty surrounding long-term complications, particularly regarding compounded versions that enter the market with minimal regulatory oversight. Given the influence of semaglutide on metabolic and neurological pathways, the potential for adverse physiological effects remains unknown. While early research report favorable outcomes, the long-term side effects of sustained use are still largely unknown (Rubino et al., 2023).

Financial and Access Barriers

The cost of GLP-1 medications represents a substantial hurdle for many individuals. With monthly cost exceeding $1,000, insurance coverage is typically limited to patients with specific medical indications (The Guardian, 2025). As a result, those seeking these medications primarily for weight loss, without a qualifying diagnosis, are sure to face unrealistic expenses. Notably, studies indicate that discontinuation often leads to significant weight regain (Wilding et al., 2022), creating a cycle where individuals may feel compelled to continue usage indefinitely.

Beyond financial burdens, the physiological adaptations induced by GLP-1 agonists, such as alterations in appetite regulation and metabolic rate, may result in significant challenges maintaining weight loss after treatment has stopped. Patients who stop using the medication often report increased hunger and difficulty sustaining prior weight loss, raising serious ethical concerns about potential dependency.

The Risks of Unregulated Alternatives

The high cost, and limited availability, of these drugs have driven some individuals toward unregulated or illicit sources. Enter compounded semaglutide. The compounded versions are produced by non-traditional pharmaceutical entities, and have entered the market with little oversight, leading to potential safety risks. These formulations have not undergone rigorous clinical trials, and their pharmacological consistency remains uncertain (U.S. Food and Drug Administration, 2024). Additionally, the illicit sale of these medications through online vendors and underground markets increases the likelihood of contamination, improper dosing, and adverse health outcomes (National Association of Boards of Pharmacy, 2024).

Ethical and Policy Considerations

The increasing “off-label” utilization of GLP-1 agonists necessitates critical ethical and regulatory discussions. Should insurance coverage be adjusted to include weight-loss indications beyond traditional metabolic disorders? What can we do to establish a framework that can assist individuals in maintaining weight loss post-treatment without promoting pharmaceutical dependency? Can policymakers strengthen oversight to prevent the proliferation of black-market alternatives to ensure patient safety?

While these medications hold promise as a tool for obesity management, their use should be confined to carefully structured treatment plans that include behavioral interventions such as diet and exercise intervention. Without comprehensive guidance, there is a risk of promoting a culture of “addicts” who feel dependent on this medication for the rest of their lives.

The Underemphasized Role of Lifestyle Interventions

One of the more concerning aspects of the GLP-1 “weight-loss trend” is the extent to which people turn to pharmacological solutions, rather than simple lifestyle modifications. Regular exercise and a nutrient-dense diet remain the cornerstones of metabolic health, offering additional benefits such as improved cardiovascular function, reduced psychological distress, and enhanced long-term weight stability (Swift et al., 2021). Research consistently demonstrates that long-term weight management is most effectively achieved through sustained dietary and physical activity interventions rather than pharmacotherapy alone (Jakicic et al., 2022).

It is unsettling that many people who choose a GLP-1 route for weight reduction, never decide to also include a structured lifestyle change. These people think that they can simply inject themselves and the weight will fall off. However, what they do not realize is that the weight loss is systemic and includes muscle loss. The rapid loss in muscle mass can create an individual who is frail and now prone to other health risks such as falling.

Regular physical activity paired with a nutrient-rich diet stands as the bedrock of metabolic vitality, yielding ancillary benefits like enhanced cardiovascular health, diminished mental strain, and greater weight stability over time (Swift et al., 2021). The healthcare community bears a duty to champion lifestyle measures as the primary recourse before turning to pharmaceutical interventions. Encouraging patients to adopt sustainable health behaviors, over quick-fix approaches, will ultimately yield superior long-term health outcomes.

Conclusion

While GLP-1 receptor agonists present a valuable option for addressing obesity and type 2 diabetes, their increasing off-label use as a weight-loss solution raises critical concerns about dependency, financial burden, and exposure to unregulated alternatives. Furthermore, the long-term effects of these medications (particularly compounded formulations) remain an area of uncertainty.

Rather than normalizing pharmaceutical reliance, healthcare providers, policymakers, and the public must engage in informed discussions on sustainable weight management. A greater emphasis on lifestyle interventions, including proper nutrition and physical activity, is essential to addressing obesity without resorting to potentially hazardous shortcuts. By proactively addressing these issues, we can mitigate the risks associated with long-term pharmaceutical dependence and promote a healthier, more sustainable approach to weight management.

References

• Jakicic, J. M., Rogers, R. J., Davis, K. K., & Collins, K. A. (2022). Role of physical activity and exercise in obesity treatment. The Journal of Clinical Endocrinology & Metabolism, 107(4), 1036-1050.

• National Association of Boards of Pharmacy. (2024). The risks of compounded GLP-1 receptor agonists. NABP Report.

• Rubino, D., Greenway, F. L., Khalid, U., O’Neil, P. M., & Wadden, T. A. (2023). Long-term effects of GLP-1 receptor agonists in obesity treatment: What we do and don’t know. Obesity Reviews, 24(2), e13528.

• Swift, D. L., McGee, J. E., Earnest, C. P., Carlisle, E., & Johannsen, N. M. (2021). The effects of exercise and physical activity on weight loss and maintenance. Progress in Cardiovascular Diseases, 67(3), 143-152.

• The Guardian. (2025). Insurance challenges for weight loss medications. The Guardian Health.

• U.S. Food and Drug Administration. (2024). Consumer warning: The dangers of unregulated compounded semaglutide. FDA Public Health Advisory.

• Wilding, J. P. H., Batterham, R. L., Davies, M., Van Gaal, L. F., Lingvay, I., & McGowan, B. M. (2022). Weight regain after withdrawal of semaglutide: A randomized clinical trial. The Lancet Diabetes & Endocrinology, 10(11), 840-849.