The entry of glucagon-like peptide-1 (GLP-1) agonists, of which semaglutide is the most widely known, has changed the dialogue surrounding the use of anti-obesity medications. There is increasing demand for semaglutide in Canada even though there are still outstanding questions about its safety, long-term effectiveness, and the degree to which it reduces outcomes associated with obesity. The rationale behind its use is based on data indicating that those prescribed the drug lose about 12% in body weight1 and the presumption that semaglutide lowers the risk of conditions associated with obesity.2 However, there is a distinction between treating obesity in the hope of reducing morbidity and using GLP-1 agonists to achieve a certain body appearance.

In this short commentary, we propose that this heightened preoccupation with obesity (and the associated main driving factors behind the popularity of semaglutide) comes from a misplaced focus on body size as a proxy for health and a pharmaceutical industry eager to sell.3

The popularity of semaglutide is strongly influenced by popular beliefs about what health looks like and what constitutes a “normal” body image—beliefs that have long infiltrated medical thinking about obesity and the way that obesity is portrayed in the media. Social preferences play an important part in both lay and medical assessment of normality and disease. As one study pointed out, “Individuals who are perceived to carry excess weight are evaluated negatively, and are often stereotyped as being lazy, unhealthy, unattractive, and inactive.”4 The pharmaceutical industry is tapping into historically conditioned beliefs about appearance in their strategies to promote disease awareness.3

Aesthetics play an important role in medical judgment about what deviates from normal. According to Stafford et al, there is an “unstated standard of what is common or average to the species … [which is] revealed in our unconscious response to people who depart measurably from that expectation.”5 How people look, or believe they should look, influences practices by patients and their health care providers, and in this case, is one of the reasons for the enthusiasm about—and corresponding overuse of—semaglutide.

Although having a higher weight might have negative health consequences, these consequences vary considerably in their severity and how they are experienced. Examining the social foundations of an obesity diagnosis can help us to recognize the different perspectives that health care professionals and patients need to consider and to contextualize our conversations about obesity and semaglutide.

Historically, obesity was a qualitative assessment of adiposity, rather than a diagnosis made by weight; however, doctors were skeptical about the ability of standardized measurements found in height and weight charts to determine the suitable weight for an individual.6 As a result, 18 different weight classification systems that have added to the qualitative nature of the assessment have been proposed between 1942 and 2000.7

The commonly used definition of obesity is a body mass index (BMI) of 30 kg/m2 or greater, which has been adopted as the criterion standard for the use of semaglutide as a treatment for obesity. (In the presence of 1 or more obesity-related comorbidities, the BMI is ≥27 kg/m2). However, this definition is problematic: First, BMI is a population measurement and does not take into consideration actual body composition. This problem is what statisticians call the “ecological fallacy,” where aggregate correlations are used to draw conclusions about individual people. A second problem is that BMI does not reflect adiposity the same way in different populations: One size does not fit all.

Finally, and probably most importantly, it is erroneous to think that overweight and mild obesity should be seen as pathological. Numerous studies have demonstrated that factors that frequently (but not always) covary with obesity (eg, good nutrition, exercise), rather than obesity and body mass per se, are the actual causes of negative health outcomes. There is a tendency to use weight as a marker for the other factors, since weight is much easier to verify in a clinical setting than nutrition or exercise.

The choice of a BMI cutoff of 30 kg/m2 as the definition of obesity is also problematic and bears the mark of the pharmaceutical industry in its choice. It is derived from a 1995 report from the World Health Organization that explicitly avoided using BMI to define obesity. The report defined grades of overweight using BMI cutoffs of 25, 30, and 40 kg/m2, describing these as largely arbitrary and noting “there are no clearly established cutoff points for fat mass or fat percentage that can be translated into cutoffs for BMI.”8 The expert panel set up in 1995 by the National Heart, Lung, and Blood Institute used the same arbitrary BMI cutoff points as the World Health Organization report, but in its 1998 report changed the terminology for a BMI of 30 kg/m2 or more from grade II to III overweight to obesity, wording that is still used today for that level of BMI.8

This outcome is unsurprising, as the chair and 3 other members of the National Heart, Lung, and Blood Institute panel were members of the International Obesity Task Force, an organization almost entirely funded by the pharmaceutical industry.8 As a New York Times article described, the panel’s finalized definition created “a booming new market for diet pills.”9

The contemporary focus on obesity uses weight as a proxy measure for health. This substitution results in poor decisions about health and stigmatization of what are normal variations in human morphology. This focus contradicts the principles of weight inclusivity promoted by the Association for Size Diversity and Health, which includes the acceptance of and respect for “the inherent diversity of body shapes and sizes” as well as the rejection of “the idealizing or pathologizing of specific weights.”10 Not only is body fat seen by many as undesirable, but being slender is overvalued, often leading to dangerous nutritional and lifestyle practices. Our societal obsession with obesity also creates a tendency for physicians to reach for the prescription pad when patients express concern about their weight, a tendency that is encouraged by drug companies, as evidenced by the amount they spend.11

While there are BMI criteria for prescribing semaglutide, it is the visual presence of body fat that plays a powerful role in the promotion of obesity as a diagnosis and the therapies designed to treat it.5 Unlike hidden risks such as hypertension, diabetes, or high cholesterol, body fat is visible and can be used in advertising messages. Over the summer of 2023, advertisements for semaglutide appeared on billboards and streetcars in Toronto, Ont, with the name of the drug and a picture of a mildly overweight woman who would not meet criteria for a semaglutide prescription.12 Such advertisements were obviously intended to both directly stimulate patient requests for the drug and indirectly shape providers’ expectations about how patients wish to be treated.

In addition to questioning whether obesity should be the focus of such intense medical fixation, the lack of attention to the safety profile of semaglutide is also pertinent. Semaglutide was initially approved for the treatment of type 2 diabetes in January 2018, being on the market long enough for any major side effects missed in the preclinical trials to be recognized.13 However, at this point there are still outstanding safety questions about the drug. The European Medicines Agency’s risk management plan for semaglutide highlights potential harmful effects for which there is suggestive evidence, but uncertainty about causation, and includes diabetic retinopathy complications, pancreatic cancer, and medullary thyroid cancer. Effects on pregnancy and lactation and on patients with severe hepatic impairment also remain unknown.14

One key question is whether the use of semaglutide improves morbidity and mortality. The SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial found an absolute risk reduction of 1.5% in a composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.2 However, death from cardiovascular causes alone, the first confirmatory secondary endpoint, was not significant (P=.07). In addition, twice as many patients discontinued semaglutide because of adverse events compared with placebo (16.6% vs 8.2%).2 Since patients typically regain weight after they discontinue semaglutide, reducing morbidity and mortality might require staying on the drug indefinitely.

The choice to prescribe semaglutide should be made carefully. The diagnosis of obesity—as clearcut as it might appear from the weight on the scales and BMI charts—is a fluid concept, contingent not just on a set of biochemical or physiologic numbers but on how those numbers are interpreted and potentially spun by pharmaceutical companies. Whether obesity is viewed as the result of a biochemical or physiological divergence from what is considered normal or of individual behavioural choices, prescribers should think carefully about patient requests for semaglutide, especially when there is incomplete knowledge about safety. When we think about how we view obesity and whether treatment with semaglutide (and the other GLP-1 agonists) is warranted and acceptable, awareness of weight stigma and normativity needs to be taken into account in reaching a decision.

Competing interests

Between 2021 and 2024, Dr Joel R. Lexchin received payments for writing a brief on the role of promotion in generating prescriptions for a legal firm, for being on a panel about pharmacare, and for co-writing an article for a peer-reviewed medical journal. He is a member of the Board of Canadian Doctors for Medicare and the Board of the Canadian Health Coalition. He receives royalties from the University of Toronto Press and James Lorimer & Company Ltd for books he has written. He is participating in research funded by the Canadian Institutes of Health Research. Dr Annemarie Jutel receives royalties from the University of Toronto Press and Johns Hopkins University Press for her books on diagnosis.

The opinions expressed in commentaries are those of the authors. Publication does not imply endorsement by the College of Family Physicians of Canada.

This article has been peer reviewed.

La traduction en français de cet article se trouve à https://www.cfp.ca dans la table des matières du numéro de février 2025 à la page e23.