Responses to Editorial on Prescribing GLP-1 Agonists for Weight Loss

We appreciate the editorial by Rao, et al., discussing the important issue of prescribing glucagon-like peptide-1 (GLP-1) agonists for weight loss.¹ Although we agree that these medications are expensive and may have unrecognized adverse effects, we disagree with many of the statements regarding the health effects of obesity. Obesity includes a range of weights, and elevated body mass index may not accurately reflect health status. However, many of our patients experience daily adverse consequences of obesity, especially morbid obesity, including joint pain, sleep apnea, and decreased exercise tolerance. In addition, these patients are at increased risk of diabetes, hypertension, and hyperlipidemia.² Morbid obesity is associated with increased mortality.³ With all this evidence, it seems clear that obesity is detrimental to health and should be addressed by family physicians.

We agree that in addition to these health effects, weight-based marginalization persists. Family physicians should be sensitive to this societal reality. Nevertheless, we should assess patients for obesity and offer assistance when the patient desires it. Long-term, even small-scale, weight loss has been shown to improve health.^4,5 Of course, health and physical fitness are more important than the number on the scale, but we cannot simply focus on the origins of cultural biases and ignore the health implications of obesity. Many patients have ongoing disability due to morbid obesity and need the best medical care possible.

In a recent editorial, the authors wrestled with a seeming conundrum: should family physicians promote weight loss in patients, when weight loss has not been shown to benefit health and can worsen patients' self-esteem? Are family physicians setting up patients for a lifetime of potentially unsafe treatment? Fortunately, this conundrum is solvable, because the assertions in this editorial are inaccurate.

To begin, by all accepted definitions, obesity meets the criteria of a disease.¹ Adipose tissue dysfunction and fat mass are strongly associated with conditions such as diabetes, cardiovascular disease, cancer, and osteoarthritis. Treating obesity has consistently been shown to reduce all-cause mortality and improve quality of life, including improving mental disorders such as depression.^2–5 Research shows that obesity treatment paradigms that do not incorporate medications are minimally successful, with patients achieving a modest 5% to 7% total weight loss.⁶

With the emergence of newer medications, including GLP-1 receptor agonists, patients with obesity can lose upwards of 15% to 20% of total body weight, achieving nearly the magnitude of weight loss seen with bariatric surgery. In turn, through facilitating substantial weight loss and via weight-independent pathways, GLP-1 receptor agonists improve glucose metabolism, cardiovascular health, kidney health, lipid disorders, liver health, and other outcomes. Beyond medications, evidence-based obesity management entails nutrition therapy, physical activity, and behavioral modification, including addressing stress, mental health, and sleep.⁷

The editorial authors correctly suggest that shared decision-making using the STEPS (safety, tolerability, effectiveness, price, simplicity) approach should be used when discussing treatment options with patients. Such discussions should, nonetheless, balance both the risks and benefits of various obesity treatment modalities. The contention that GLP-1 receptor agonists have unknown long-term safety is inaccurate. Because the first commercial GLP-1 receptor agonist was released in 2005, we have 20 years of safety data on this medication class.⁷ Finally, the authors' caution about weight-based marginalization and weight-focused culture, although legitimate, fails to acknowledge that treating obesity does not exclude sensitivity toward complex cultural notions of beauty and fitness.

As practicing obesity medicine physicians, we submit that the conversation about obesity care should focus not on ideological uneasiness but on evidence-based, comprehensive, patient-centered management of the disease. Family medicine physicians are well-suited to lead the way in this endeavor.

We appreciate the responses to our editorial “Prescribing GLP-1 Agonists for Weight Loss: Wrestling With Our Philosophical Angst.” We suggested that the treatment of obesity warrants a paradigm shift. Like any transformational concept, this one requires critically reevaluating and reflecting on our understanding, beliefs, and biases before more readily embracing a markedly different worldview.

Although body size is one of innumerable factors entwined with the development of chronic disease, it is not a reliable indicator of health and should not be the focus of treatment. External attributes cannot be conflated with internal health markers. A large proportion of people labeled as obese are considered metabolically healthy with normal A1C, lipids, and blood pressure. On the other hand, people who are thin and have metabolic dysregulation are often overlooked.¹

We suggested in our editorial that a primary goal of weight loss is unsustainable and misguided. Human bodies have evolutionarily adapted to conserve body mass for survival. Short-term weight loss (through use of medications or dieting) is almost always followed by weight regain after 3 to 5 years.² Subsequent weight cycling often leads to long-term harm and further metabolic dysregulation.³ Body mass reduction alone does not cause adaptive metabolic changes. For instance, surgical fat removal does not provide the same metabolic reprogramming as a sustained increase in aerobic activity and intentional nourishment.⁴

Physicians should encourage patients to engage in healthy behaviors, which, if sustained, confer long-term health benefits regardless of weight change. Weight-neutral interventions (ie, those performed without the explicit purpose of resulting in weight change) are noninferior to weight-loss interventions for end points such as blood pressure, glycemic control, and lipid levels and benefit quality of life and mental health.⁵ Weight-centric care, however, leads to health inequities due to avoidance of medical care and delayed diagnosis. It also impacts mental health and encourages chronic dieting, weight cycling, and disordered eating.⁶

So where does treatment with GLP-1 agonists fall within this framework? Some patients may feel that taking weight loss medications is their only gateway to behavior change. When taken for other conditions such as diabetes and heart disease, patients may view the weight-related effects as stigma-reducing. If used, GLP-1 agonists should be carefully incorporated with weight-neutral counseling, but they are not necessary, should not be traded for healthy behaviors, and should be prescribed responsibly and with respect to patients' bodily autonomy.