by Cynthia Bulik, PhD, FAED, Founding Director of CEED
Back in August 2023, I was invited to write this editorial on Ozempic for Science, which I co-wrote with former UNC CEED neuroscience post-doc Andrew Hardaway. It was challenging…very challenging. I drafted a companion blog that elaborated on many of the topics that we were only able to touch upon in the editorial, but every time I was about to post it, some new information about about semaglutide and its cousins hit the medical literature and lay press. For those of you who have not been bombarded by information about these drugs, the GLP-1 receptor agonists (GLPs for convenience) that have been used to treat type 2 diabetes for quite some time, are now being widely prescribed for weight loss, with impressive results. Common names are Ozempic, Wegovy, Saxenda, and Mounjaro. Recently I started getting daily FB ads promising “semaglutide delivered to your door overnight,” so, I decided to try once again.
When we wrote the editorial, one issue that concerned us was whether these were basically “lifestyle” drugs, or meds that were going to be widely abused by people who didn’t need them to control their diabetes to achieve some thin body ideal. Indeed, plenty of stories have emerged about celebrities, influencers, and Los Angelinos (apologies to my LA friends) taking the meds like injectable candy. This is definitely still a concern; however, convincing clinical trials have now demonstrated positive cardiometabolic effects beyond weight loss itself. Ozempic does indeed lower the risk of stroke, heart attack, and death in individuals with cardiovascular disease. This was a very important outcome and served to transition opinions about the medications as something that can help you lose weight and keep it off, to something that can not only help you lose weight, but also reduce your risk of serious cardiovascular outcomes.
As a brief aside, most feedback that I got from readers was related to adverse side effects of the medications. So, I will underscore here, that these medications are not benign, and serious side effects occur, most commonly gastrointestinal, and they are being monitored by regulatory agencies due to many reports of suicidality.
Another issue that we grappled with was how proponents of many of the movements such as Health at Every SizeTM, body positivity, fat activism, and other groups that have worked tirelessly to combat stigma and discrimination against people living in larger bodies were going to look upon these drugs. For example, would someone who found acceptance in these groups be free to take the medications without shame? Is taking the medications for weight loss consistent with a philosophy of body acceptance? Is there still a place for these groups, or will the widespread use of these medications actually lead to a new flavor of discrimination, “Why would someone CHOOSE to remain fat when these medications are widely available?” In much the same vein as questioning why someone with hypertension would CHOOSE to continue to have high blood pressure when so many effective medications exist.
Even more pointedly, with these medications in the physicians’ armamentarium, do we need to re-imagine the practice weight-inclusive healthcare? Weight-inclusive healthcare is defined by the Rudd Center for Food Policy and Obesity as “encouraging emotional, physical, nutritional, and social health without emphasizing weight.” If a high weight patient with hypertension, high cholesterol, joint problems, and fatty liver sought weight-inclusive healthcare, does it remain ethical to do so when medications are available that can address all of these serious health concerns at once? These are big questions that we should all be talking about.
We further questioned the meaning for what it meant for these functionally to be “lifetime drugs,” meaning that you have to stay on them forever. Especially given the clearly documented causal effects of highly processed foods, sugar-sweetened beverages, and ever-increasing portion sizes on global weight dysregulation, are we actually just developing medications to counter problems that are in part caused by the rich and influential Big Food and Big Beverage companies? Are we once again placing blame on the consumer and burdening them with having to pay for and take a medication for life in order to successfully avoid the scientifically developed highly addictive foods that surround us? Are we actually victims of a prolonged battle between Big Pharma and Big Food and Beverage? The widespread use of these medications will definitely have an impact on our consumption of Jumbo size anything. As pharma’s coffers become increasingly bloated by profits from these drugs, the food and beverage companies R&D departments are going to have to be working at breakneck pace to find ways to bypass the appetite STOP sign raised by the GLPs.
One of the biggest concerns we noted, that is even further amplified by the documented positive cardiometabolic protective effects of these medications, is equal access. The drugs are costly (up to $1300/month) and in high demand, meaning that availability is variable (despite the promises of FB ads!). The metabolic and psychological impact of starting and stopping the medications due to availability or affordability is unknown. Many insurance companies and employers are backing down from covering the GLPs for weight loss, meaning massive out of pocket expenditures will be required. Although high weight and co-occurring medical conditions affect individuals across the socioeconomic and cultural spectra, they disproportionately affect those in lower socioeconomic strata and who belong to minoritized groups. These medications, their affordability, and their accessibility have very real potential for further exacerbating health disparities. This is an urgent issue that critically requires attention by commercial and public insurers, employers, and the pharmaceutical industries that manufacture the medications.
With reference to individuals with eating disorders, I see two opposing issues. First, anecdotal reports from individuals with binge-type eating disorders suggest that the GLPs reduce or even eliminate the urge to binge. Even more intriguingly, some people whose lives and thoughts have been dominated by food for years if not decades, say that the medications have a profound cognitive effect that it is like changing the channel on a TV. The soundtrack of their minds completely changes, eliminating the constant food noise that fed their eating disorder. A few preliminary studies have shown limited promise (Bartel et al., 2023), but much larger controlled trials are necessary to fully evaluate the potential of these medications in treating binge-type eating disorders. As with any weight-loss intervention, outcomes must be strictly monitored to capture both known side effects, but given their extreme impact on appetite, desire to eat, and weight loss, monitoring signs of transitioning to a restrictive eating disorder profile. Extreme caution should guide prescribing these medications to any patient with a history of anorexia nervosa given the very clear potential of negative energy balance to trigger relapse.
The second issue relative to eating disorders is the potential for abuse. As an eating disorders specialist, this scares me enormously. I cannot overemphasize the vigilance that clinicians and carers should maintain about the misuse of these drugs. It is not a stretch to anticipate them having serious if not fatal consequences in very underweight individuals. Currently these medications are injectable, which may minimally decrease the likelihood of abuse. But ingestible forms will invariably appear, removing that barrier. The GLPs could be misused by people with restrictive eating disorders, by athletes in sports where weight is regulated or offers aesthetic advantage, and in professions where the same principles apply.
The bottom line is that these drugs are with us now and have enormous potential—even though we don’t entirely know how they work. New variations will appear on the market that are easier to administer (i.e., oral) and have more favorable profiles (e.g., preserve muscle mass during weight loss). On balance, the availability of these medications is a plus. They will save lives and improve the health of millions of people—at least those who can access and afford them. Moreover, the rush to fully understand their biology and their mechanisms of action is opening new corners of science that are unlocking the complex biology of appetite and weight dysregulation. Given the abysmal state of medications for anorexia nervosa (i.e., there are none), this work may also shed light on developing medications to help individuals trapped in the anorexia whirlpool to gain weight and restore appetite and metabolic function. However, the issues of health equity, abuse potential, and the impact of cycles of starting and stopping the medication require urgent attention to ensure that their benefit to the world remains a net positive.
It’s a transformative time in healthcare. We need to have hard conversations about all of these topics, many of which are quite sensitive. Respectful discourse and deep listening will be key to defining a path forward that acknowledges many valid and valuable perspectives as we work toward integrating these medications into our world views.
References
Bartel, S., McElroy, S. L., Levangie, D., & Keshen, A. (2023). Use of glucagon-like peptide-1 receptor agonists in eating disorder populations. Int J Eat Disord. https://doi.org/10.1002/eat.24109
Further reading (some may be behind paywalls unfortunately):
https://www.science.org/doi/10.1126/science.adj9953
https://www.science.org/content/article/breakthrough-of-the-year-2023
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