Obesity and the associated morbidity and mortality have long been a significant chronic disease challenge for healthcare systems worldwide. Current treatment options use lifestyle modifications, medication, or bariatric surgery to induce a negative energy balance. While medications for obesity have been available for decades, healthcare providers have often been hesitant to prescribe them due to concerns about potential side effects and the necessity of long-term use. However, it is important to recognize that side effects of medications are a common possibility, and yet medications are prescribed when their benefits outweigh the potential risks. Not treating obesity effectively also poses its own risk, which needs to be recognized when considering obesity medications. Similarly, a chronic disease such as obesity needs chronic treatment, including medications, if indicated, much the same as lifelong treatment for diabetes, another chronic disease.

In the past, pharmacotherapy of obesity has suffered some setbacks due to the side effect profile of medications. However, recent advancements in understanding the gut-brain axis and weight regulation mechanisms have ushered in a new era of transformative therapies. These developments are reflected in this special edition of the International Journal of Obesity, which explores the practical use of current and emergent drugs, considerations for their increased adoption, and future directions for research and clinical practice.

The practical applications of obesity management drugs extend to special populations like older adults and children, who face unique challenges in obesity management. In geriatric populations, Henney and his team review the growing evidence supporting the safety and efficacy of intentional weight loss with obesity management drugs [1]. These drugs reduce cardiometabolic risks while addressing concerns about muscle and bone mass preservation, making them a viable option for older adults whose health has already been affected by age-related decline. These drugs are not only effective in facilitating weight loss but also hold promise for preserving muscle mass, an essential factor for metabolic health and long-term weight maintenance. As highlighted in the review by Argyrakopoulou et al. [2], emerging evidence suggests these drugs positively influence body composition, making them an important tool in individualized treatment plans, especially in older individuals (for which preserving muscle mass is a challenge). For pediatric populations, Fox et al. explore how obesity management drugs fill the treatment gap between lifestyle modifications (traditionally the milestone for the treatment of children with obesity) and bariatric surgery (which is often not accessible and/or desired by families) [3]. Recent clinical trials have demonstrated the safety and efficacy of these medications in children and adolescents, which resulted in official recommendations by the American Academy of Pediatrics to enable healthcare providers to offer pharmacotherapy as part of a comprehensive obesity management strategy. Together, these studies underscore the expanding role of obesity management drugs across the lifespan, emphasizing their versatility and potential for improving health outcomes.

While the benefits of obesity management drugs are clear, their adoption comes with several challenges to be considered. More available and widespread information with strong endorsement from healthcare providers is essential. Craig et al. [4] identify factors influencing patients’ decisions to pursue pharmacotherapy, including the efficacy, side effects, cost, and reassurance from healthcare providers. The safety of obesity management drugs is frequently discussed within the medical profession and also between patients and healthcare providers. Vidal et al. [5] provide a comprehensive review of the safety profiles of gut-hormone receptor agonists, affirming their favorable balance between efficacy and safety. However, they stress the importance of continuous surveillance to identify potential long-term risks, particularly as these drugs are used in broader populations with multiple chronic diseases. Addressing patient perspectives through patient-centered approaches can enhance adherence and optimize outcomes. An opportunity described by Başaran et al. [6] represents the use of GLP-1 receptor agonists in addressing weight regain after bariatric surgery to sustain weight loss in this population. As bariatric surgery remains the option for many patients with obesity, pharmacotherapy could serve as a valuable adjunct, mitigating metabolic adaptations and improving long-term outcomes.

Behavioral changes associated with or recommended alongside obesity management drugs are another important consideration for the treatment adoption by patients. Bettadapura summarizes evidence showing that GLP-1 analogs not only reduce appetite but also influence food ingestive behaviors in the weight loss phase [7]. However, these changes are self-reported and not studied during the weight maintenance phase. More objective data and long-term data will provide significant advantages for the adoption of obesity management drugs. Murphy and Finucane notice in their review [8] that even though lifestyle changes are recommended with all obesity management drugs and have the potential to augment the efficacy of obesity management drugs while addressing broader health concerns, there are no trials to demonstrate the additive benefits of combining these approaches.

The future of obesity management drugs is marked by exciting opportunities and development. Melson et al. [9] outline the promising pipeline of next-generation drugs, including dual and triple hormone receptor agonists that approach the weight loss efficacy of bariatric surgery. These innovations, such as cagrisema (GLP-1/amylin RA) and retatrutide (GLP-1/GIP/glucagon RA), represent a significant leap forward in treatment options for patients with obesity. Looking ahead, continued research into the mechanisms, safety, and cost-effectiveness of these drugs in various populations with multiple health conditions will be essential. As the field advances, the integration of obesity management drugs and other treatment modalities will remain a priority, ensuring that care is both comprehensive and personalized. The advent of next-generation obesity pharmacotherapy is a transformative moment in healthcare, offering hope for millions living with obesity. The studies in this special edition reflect the complexity and potential of this new era, emphasizing the need for collaborative efforts among clinicians, researchers, and patients. By doing so, it is hoped that we can transform obesity from a growing epidemic into a manageable condition, improving the lives of countless individuals worldwide.