The Dark Side of the GLP-1 Weight Loss Drugs: Eating Disorders

There has been much fanfare about the acquisition by Pfizer of Metsera, the developer of injectable and oral GLP-1 agonists and other peptides for the treatment of obesity.

The $10 billion price tag, the bidding war with Novo Nordisk, the lawsuits, it all made for high drama. It was a moment of vindication for biotechs that have struggled for years through a harsh downturn.

At the same time, Secretary of Health and Human Services Robert F. Kennedy Jr. and President Trump have secured commitments from Eli Lilly and Novo Nordisk that would limit the cost of GLP-1 drugs to $150 per month. The stated intent is to dramatically increase access for patients who need to lose weight.

Constraining the growth of the obesity epidemic has undeniable benefits for health and healthcare at the individual and population levels, linked to lower blood pressure, lower risk of heart attack and stroke, improved control of blood sugar, lower risk of kidney disease, blunted desire for alcohol and maybe even protective effects against neurodegenerative diseases.

There’s a long list of benefits.

It’s easy, in this context, to understand the frenzy that has led to vast investment in this space and an expectation for outsized returns. This feels like a wonder drug: for patients, investors and for companies.

And yet, there are two sides to every story.

The Risks

These drugs were FDA-approved to treat type 2 diabetes and obesity, but they are increasingly used to achieve and maintain slimness in the absence of either. A growing proportion of people using GLP-1s are healthy people with normal weight, or even who are underweight. And perhaps most disturbingly, while GLP-1 drugs show anecdotal evidence in the treatment of binge eating disorder, these drugs are also widely recognized to exacerbate eating disorders characterized by restriction, most notably anorexia nervosa.

GLP-1 agonists have a complex mechanism of action, but in essence they are effective weight loss medications because they mimic satiety signals in the brain and slow gastric emptying, making people feel full, and often nauseated, with very small meals. It isn’t uncommon for patients to consume a fraction of the calories required for their age over months or years. People on GLP-1 agonists frequently develop nutrient deficiencies, electrolyte abnormalities, orthostatic hypotension, osteopenia, sarcopenia, thinning hair and other signs of malnutrition.

It is not surprising then, that some people who either have a history of disordered eating or who are biologically predisposed to anorexia, spiral quickly into a dangerous cycle of restriction, weight loss and positive societal reinforcement for their new thinness. Complicating the picture is the fact that only 6% of eating disorder diagnoses occur in people who are medically recognized as being underweight; indeed those with higher BMIs are at very high risk of both developing eating disorders on GLP-1s and of not rising to the attention of medical providers who receive little to no training in eating disorders and do not typically think of people in larger bodies when they conjure what an eating disorder “looks like”.

How Much Access is Too Much?

More troubling is the ease with which women with already thin bodies can obtain GLP-1 agonists without ever seeing or speaking to a healthcare professional. Online sites like hers.com will ship semaglutide and other drugs without requiring patients to ever communicate with a healthcare professional or confirming that patients fulfill labeling requirements (it took me less than two minutes to get to the payment page after providing false information about my weight, age, medical history and goals at every step to get there). 

With little oversight, compound pharmacies have also sprung up to help fill the growing demand of GLP-1 agonists as “lifestyle drugs”. Instagram and TikTok abound with videos of young women with normal size bodies extoling the values of slimming down even further with GLP-1 agonists or “microdosing” to achieve weight loss in the setting of a low or normal BMI.

Anorexia nervosa is defined by the DSM-5 as the restriction of energy intake relative to requirements, leading to a significant low body weight in the context of age, sex, developmental trajectory, and physical health, with an intense fear of gaining weight or becoming fat, or persistent behavior that interferes with weight gain. The documented prevalence of anorexia nervosa, a dramatic underestimation, is about 4% globally – or 150 million people. 

Of all the neuropsychiatric disorders we know of, anorexia nervosa has the highest mortality rate with 5% of those affected dying within four years of initial diagnosis. It affects mainly girls, mainly around puberty, and can kill them directly via acute effects of starvation, including dangerous abnormal heart rhythms, inability to maintain sufficient blood sugar, blood pressure and heart rate, or by taking its toll chronically on the heart, brain, bones, and muscles. Or, at any time, simply by suicide.

Rigorous studies about the incidence of eating disorders in people taking GLP-1 agonists are lacking, but the risk of these drugs driving restrictive eating disorders is broadly recognized, with some estimates as high as one-third (35 percent) of new diagnoses of eating disorders coming from people on GLP-1 agonists. In a large sample of de-identified health records in people taking GLP-1 agonists, patients with any pre-existing mental health condition had more than double the risk of those who did not of developing an eating disorder in two years. The cumulative incidence in both groups of a new eating disorder diagnosis (mainly anorexia nervosa) was 1.275%. With one in 8 Americans – or approximately 43 million people – now taking GLP-1 agonists, this translates to over 500,000 people.

With increased access, cheaper prices and the growing off-label use of these drugs in vulnerable populations to achieve thinness, we’re going to see more people with eating disorders.

Seeking the Other Side of the Story

As physicians, trialists, regulators, policymakers and indeed as an industry, we are completely unprepared for this oncoming wave. There is no standard protocol to screen people for a history of eating disorders or disordered eating behaviors prior to prescribing these drugs. As far as I can tell, there is no safety database or real-world evidence study that is specifically targeted to assess this outcome, which, by virtue of its complexity, would not be expected to be passively captured in a typical adverse event assessment.

Novo Nordisk’s semaglutide (Wegovy) and similar drug labels do not include a warning for the risk of triggering restrictive eating disorders. There is no structure in practice for routine clinical follow-up that would capture these events in a systematic way so as to add to a safety database. Many of our patients may be taking these drugs without our knowledge, having obtained them online from any number of willing suppliers.

How is it, that as an industry, we have invested trillions of dollars in GLP-1 agonists and related drugs without paying attention to what this pandora’s box has unleashed? How do we have multiple approved products, dozens in late-stage clinical trials, new companies getting funded in the space seemingly every day and a frenzy of M&A activity, but not a single approved medication to help the millions of people who struggle with, and die from, anorexia nervosa every year?

Like all stories with two sides, one is typically not true to the exclusion of the other. The good stories, the ones with really compelling endings, strike a balance. The GLP-1 medicines can be a godsend for some people, and a nightmare for others.

The increasing understanding of the underlying GLP-1 biology may also point us in surprising new directions. Anorexia nervosa is not the inverse of obesity, but like obesity, it is now recognized as a complex medical and psychiatric illness. There are important areas of mechanistic overlap in the underlying biology. In a time of growing ubiquity of GLP-1 drugs, we can learn from this shared foundation to help identify druggable targets.

In a world that chronically underinvests in women’s health, could we leverage the GLP-1 wins to put effort into minimizing the devastating consequences of obesity’s metabolic cousin, anorexia, that ironically has been exacerbated by the use and abuse of GLP-1 agonists? As an industry, could we provide support to change a culture that values thinness at any cost?

As a physician, a drug developer and a mom of a daughter in recovery for anorexia nervosa, I remain hopeful that the answer is yes.