GLP-1 Receptor Agonists: Benefits and Potential Risks

The rising use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has led to an increased understanding of their diverse effects. These medications, which have been effectively utilized for treating conditions like type 2 diabetes and short bowel syndrome for decades, are gaining attention for their potential to assist in treating obesity. Notably, drugs such as Ozempic, Wegovy, and Mounjaro have become prominent names in this field. Recent FDA approval of oral GLP-1RAs, like Novo Nordisk’s Wegovy, is expected to boost their use further. A KFF Health Track survey conducted in November 2025 indicated that around 12% of U.S. adults were using GLP-1RAs for weight management or chronic health issues. The availability of pill-form medications could potentially increase that figure to 40% by 2026, based on data from Sunlight.com.

In addition to addressing obesity, researchers and healthcare providers are uncovering various other applications for GLP-1RAs. Reports show that these medications can help reduce dependence on substances like alcohol and drugs, with some clinicians reporting their effectiveness in treating behavioral addictions to gambling and sex. A notable study published in the Journal of the Endocrine Society (JES) in October 2025 highlighted the potential for GLP-1RAs to aid in managing alcohol and substance use disorders.

The authors of the JES paper discuss the observable correlation between obesity and addiction, a topic that can generate controversy. They note that certain characteristics of obesity can mimic addiction, including shared neurocircuitry mechanisms. "Pathways implicated in addiction also contribute to obesity," the authors state. Lorenzo Leggio, MD, PhD, clinical director at the National Institute on Drug Abuse, emphasized this connection, stating that neuroimaging has shown overlapping features in both addiction and obesity cases. Investigations into gut-brain neuroendocrine pathways suggest these might influence alcohol use disorder (AUD), indicating that gut-brain signaling could become a target for new treatment avenues. Leggio’s lab focuses on how these pathways may intersect with appetite regulation.

Despite the potential benefits, the authors acknowledged that addiction and substance use disorders often carry a stigma, which can hinder treatment. They advocate for increased education in addiction medicine during medical training, aiming to equip clinicians to recognize these disorders with the same urgency as conditions like hypertension and diabetes. Leggio articulates that dismantling stigma is crucial to allow current and future addiction treatments to reach their full potential.

The discussion extends to the effects of GLP-1RAs on substance use, with considerable preclinical evidence indicating their capacity to decrease alcohol intake in rodent and nonhuman primate studies. Moreover, anecdotal evidence from patients suggests GLP-1RAs can lower alcohol consumption, although the authors caution that these reports do not constitute clinical evidence and should not prompt changes in treatment protocols.

The complexities surrounding substance use disorders necessitate that they be viewed not merely as behavioral issues but as chronic medical conditions, akin to diabetes or hypertension. The authors highlight the need for large-scale randomized controlled trials to establish how effectively GLP-1RAs can manage these disorders and identify which patients may benefit most.

On another note, the manuscript published in JCEM Case Reports in February 2025 describes an acute case involving a patient who developed euglycemic ketoacidosis after being treated with both an SGLT2 inhibitor and tirzepatide, a newer GLP-1 receptor agonist. The report indicates a possible synergistic effect between these two drugs that maintained blood sugar control while inducing ketone production and systemic acidification, necessitating the patient’s ICU admission for treatment.

Eli J. Louwagie, MD, PhD, of LewisGale Hospital Montgomery, cautions about this rare but serious complication and stresses that clinicians should remain vigilant for signs of ketoacidosis in patients receiving tirzepatide, especially those also on SGLT2 inhibitors. Louwagie notes that the interaction of these medications warrants further research due to their increasing application in clinical settings.

Furthermore, the usage of GLP-1RAs has generally displayed a favorable safety profile. However, Louwagie emphasizes the importance of understanding all potential side effects, particularly the rarer ones, to avoid adverse outcomes as the usage of these medications continues to rise. This reinforces the need for personalized medicine approaches.

In a commentary associated with Louwagie's case, Christine Rode Schwarz, PhD, and her co-authors advocate for a careful balance when prescribing GLP-1-based therapies. They state that, while acknowledging the documented beneficial outcomes associated with these treatments, every patient’s unique circumstances must be considered to avoid complications. Significant benefits in glycemic control, weight loss, and even reduced cardiovascular risk are cited, along with an appeal for continued individualized patient care in practice.

Both Louwagie and Schwarz agree on the necessity for tailored treatment methods, noting the diverse responses among patients to GLP-1RAs. While many patients have experienced success without significant adverse effects when combining these therapies, understanding individual risk factors remains vital in ensuring optimal outcomes. The advancement in treatment options represents a significant development in managing chronic conditions, but this progress must be matched by comprehensive knowledge of their implications and risks.