GLP-1 Receptor Agonists: Trend, Necessity, or Blessing?

ABSTRACT

The recent endorsement of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (Wegovy), by the American College of Cardiology as first-line therapy for weight management marks a paradigm shift in cardiometabolic care. Semaglutide offers significant benefits, including improved glycemic control and substantial weight loss, with emerging data demonstrating its impact even in individuals without diabetes. However, GLP-1 receptor agonists’ growing popularity raises important concerns regarding long-term safety, access equity, and health care priorities. Although common adverse effects are gastrointestinal, less frequent but serious risks such as gallbladder disease, pancreatitis, and anesthesia-related complications deserve attention. Obesity, a global epidemic, has traditionally been managed through lifestyle interventions. The increasing reliance on pharmacologic options must not overshadow the foundational role of diet, physical activity, and education. Although GLP-1 receptor agonists represent a powerful advancement in obesity and cardiovascular risk management, its widespread adoption demands a balanced, evidence-based approach that integrates it into a broader, patient-centered strategy. There is a pressing need for comprehensive care models that address both the physiological and behavioral aspects of obesity. As health care systems navigate this therapeutic shift, they must ensure ethical use, cost-effectiveness, and long-term safety. GLP-1 receptor agonists may indeed be a blessing, but only if applied judiciously within the context of holistic obesity management.

Am J Manag Care. 2025;31(Spec. No. 15):SP1084-SP1085

The American College of Cardiology’s recent endorsement of glucagon-like peptide-1 (GLP-1) receptor agonists as a first-line therapy for weight management in individuals with cardiometabolic risk represents a major shift in clinical guidance.¹ This reflects growing evidence of these drugs’ efficacy in helping patients achieve significant weight loss and reduce cardiovascular risk. This has undoubtedly transformed our therapeutic landscape. However, could the growing enthusiasm for pharmacologic agents overshadow the critical role of lifestyle-based interventions in obesity management?

Addressing obesity is a public health priority, as it increases the risk of metabolic disease, cardiovascular disease, and various malignancies.² For decades, the cornerstone of managing obesity and its comorbidities has been behavioral and lifestyle changes—nutritional improvements, physical activity, and patient education. Pharmacologic interventions were historically reserved for individuals who did not respond to lifestyle modifications alone.

GLP-1 receptor agonists such as semaglutide (Wegovy) prompt a significant increase in insulin secretion and suppression of glucagon release, which is beneficial for controlling blood glucose levels and supports weight loss by delaying gastric emptying and decreasing appetite.³
A meta-analysis conducted by Moiz et al demonstrated significant decreases in long-term relative (weighted mean difference, –12.1%; 95% CI, –13.5% to –10.7%) and absolute (weighted mean difference, –12.3 kg; 95% CI, –13.6 to –11.0) body weight associated with its use in patients without diabetes.⁴

Common adverse effects are primarily gastrointestinal (eg, nausea, diarrhea, constipation, and vomiting), whereas more serious but less frequent adverse events include gallbladder disorders and acute pancreatitis. Emerging concerns also include increased aspiration risk during anesthesia and difficulties with bowel preparation for procedures such as colonoscopies due to delayed gastric emptying.⁵

As the use of GLP-1 therapies expands, there is an urgent need for long-term safety data. The widespread availability of compounded versions and easy access through medical spas raise serious concerns about misuse, particularly among individuals with body dysmorphia or eating disorders such as anorexia. In cases of resistant weight loss, underlying medical conditions such as insulin resistance or thyroid dysfunction should be investigated before turning to medication. For individuals with a history of eating disorders, it is especially important to consult both an eating disorder specialist and a medical provider (eg, general practitioner or endocrinologist) before starting GLP-1 therapy. If GLP-1 is deemed appropriate, clear treatment goals should be established, with regular follow-ups to monitor changes in symptoms. Compounded GLP-1 formulations should be treated as a regulated substance because they often contain additional claimed metabolism enhancers such as vitamin B₁₂ and nicotinamide adenine dinucleotide.⁶

Only licensed medical professionals should prescribe GLP-1 receptor agonists, and they must ensure regular follow-up. Supervised community-based clinical trials are needed for accountability and to understand drug interactions, adverse effects, and complications.

In the excitement surrounding breakthrough therapies, let us not forget the foundational principles of patient-centered care: empowerment, education, and prevention. Perhaps these drugs are indeed a blessing—but only if we use them wisely, as part of a broader, more holistic strategy. Marketing strategies should emphasize that GLP-1 receptor agonists are medications, not a miracle or magic solution, so that patients maintain realistic expectations and adhere to proper dosing and necessary lifestyle modifications.

Author Affiliations: Department of Radiology, Massachusetts General Hospital (NS), Boston, MA; Dow Medical College (NA), Karachi, Pakistan; Department of Neurology, PeaceHealth Southwest Medical Center (MS), Vancouver, WA.

Source of Funding: None.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MS); drafting of the manuscript (NS, NA); critical revision of the manuscript for important intellectual content (NS, NA, MS); and supervision (NS, NA, MS).

Send Correspondence to: Naveen Azhar, MBBS, Dow Medical College, House No. A-137, Block 1 FB Area, Karachi, Pakistan. Email: naveen.azhar40@gmail.com.

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