Anti-Obesity Medications: Allies or Adversaries in Population Health?

Despite our best public health efforts (and a zealous diet industry), the rising tide of obesity continues unabated. New classes of diabetes medications known as GLP-1 (glucagon-like peptide) and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists cause significant weight loss, capturing the attention of scientists, celebrities, and the public alike.  While it is still early, these therapeutics represent a potential turning point in the effective medical treatment of obesity. No previous interventions have achieved comparable levels of success at sustained weight loss, except for bariatric surgery, an invasive treatment. But the excitement about these new drugs is tempered by concerns about high costs, potential serious side effects, the need to stay on the drugs indefinitely to maintain weight loss, and yet unknown longer-term effects. Nonetheless, the magnitude and breadth of the effects from these drugs thus far means public health should take seriously the role that medicine could play in combatting obesity moving forward.

Rising obesity and population health

From 1980 to 2018, obesity (Body Mass Index, BMI ³ 30 kg/m²) prevalence in the United States climbed from 15% to 42% and severe obesity (BMI ³ 40) climbed from 1% to 10%.¹ These trends mean that having a BMI not classified as overweight or obese (BMI ³ 25) has become increasingly rare, dropping from over 50% to almost 25% during that period.  These dramatic increases in obesity are accelerating rather than slowing. Following the United States’s lead, obesity levels have climbed in most countries globally. Besides mortality, obesity is strongly associated with a range of disabling health outcomes, including diabetes, cardiovascular disease, cancer, and musculoskeletal disorders. While obesity is not synonymous with poor health, “metabolically healthy” obese people are at much higher risk of progressing to poor health than metabolically healthy non-obese people. Younger generations are also becoming obese earlier in their lives, leading to a longer duration of exposure to obesity across their lifetimes and related health risks. The consequences of these trends are serious, with obesity implicated in stalling and declining life expectancy after decades of sustained improvements. One study estimated that the effects of rising BMI since 1988 accounted for 186,000 excess US deaths in 2011, a number that is likely increasing each year.²

A New Hope?

GLP-1 medicines help treat Type II diabetes through their impact on insulin and glucose regulation. They also slow gastric emptying and are associated with significant body weight loss (an average of 10-15% in clinical trials) by reducing appetite and overall energy intake.³ Significant weight loss was seen in both those with and without diabetes and for up to four years of follow-up.⁴ Evidence is emerging on significant benefits of GLP-1 drugs beyond glucose and weight control, such as reductions in cardiovascular events and kidney disease, which may be related to reductions in systemic inflammation.⁵ These effects are thought to be independent of the effects of weight loss since they are seen early in treatment and for patients with varying degrees of weight loss. Additional intriguing evidence suggests that GLP-1 agonists may impact reward pathways in the brain and reduce cravings not only for food but also for other addictive substances. Clinical trials are underway testing the drug’s impact on the consumption of cigarettes, alcohol, and opioids. Overall, the potential of these drugs to transform population health is substantial, with new data coming out at a fast pace.

Medical vs. Social Approaches to Obesity

Despite the “game-changing” potential of these new drugs, a pharmaceutical solution to obesity raises valid concerns for many. First, the drugs may take the focus off the underlying structural causes of the obesity epidemic, which are the primary target of public health efforts to combat the epidemic. While medicine (and the media) often attribute obesity to individual health behaviors, many social and economic factors shape and constrain people’s lifestyle choices. To explain rising obesity levels, public health has traditionally pointed to the salience of environmental changes, such as the expansion of industrialized food production and increasingly sedentary occupations that make it increasingly difficult to maintain a healthy weight. Despite the potential of targeting “upstream” structural determinants of obesity, not a single country has been able to bend the curve and reverse its obesity epidemic through public health or policy measures. This failure is sobering to population health scientists, who saw success in reducing major risk factors, such as smoking over the past 50 years. While “Big Food” has been likened to “Big Tobacco,” the policy playbook for smoking has not been easily transferable to public health efforts to reduce obesity. Unlike smoking, everyone needs to eat, and the line between “good” and “bad” food is not clear. Despite this challenge, there is growing evidence for policies that improve dietary quality through taxation of sugar-sweetened beverages, front-of-pack nutritional labeling, and improving nutritional quality and education in schools. Overall, the potential for systemic changes that reduce food intake and increase physical activity has not been fully realized. However, this failure highlights the inherent difficulty in changing environments driven by globalization and technological advances. In addition, once obese, it is very difficult to revert to not being obese due to the body’s regulatory mechanisms, which work hard to hold on to fat mass. While widespread implementation of promising policies could potentially slow the growth of the obesity epidemic, it is unlikely to move the needle for the large proportion of the population that is already obese. Investments in structural changes to our food and physical environments may pay more dividends in preventing or delaying obesity for those who are not already overweight or obese, but the results of those efforts have also been lackluster thus far.

Complementary Approaches

We agree wholeheartedly with the need to address the broader social determinants of obesity, especially to prevent younger generations from first becoming obese. Nonetheless, public health and other population-based public policies to combat the obesity epidemic have not lived up to their promises, and the consequences of this failure are becoming more dire. Rising obesity was first proposed as a risk to future US life expectancy improvements more than 20 years ago,⁶ which many found overly pessimistic at the time. In the interim, gains in US life expectancy have dramatically slowed or even reversed and have increasingly diverged from other high-income countries. This stalling in US life expectancy has been largely driven by adverse trends in cardiovascular (CVD) mortality.⁷ To a lesser extent, stagnation in CVD mortality improvements is also occurring in several high-income countries, suggesting that the United States may be at the leading edge of longer-term consequences of the global obesity epidemic. Beyond mortality, younger generations in the United States may be less healthy and more disabled than previous generations at the same age due to greater exposure to obesity across their lives. As the cohorts most exposed to rising obesity reach mid-life and older age, this deterioration in health will lead to tremendous social and economic burdens as well as lower quality of life for those aging with obesity.

Given the high stakes, we believe that medical approaches to treating obesity should not be considered anathema to a population health perspective, but a potentially powerful ally. The existence of effective medications need not diminish the value of “upstream” policy approaches for preventing obesity. Broader use of new GLP-1 agonist medications also need not displace efforts to promote healthy eating and physical activity at the individual level. These approaches can be complementary by making physical activity easier after initial weight loss, and potentially reducing cravings for unhealthy foods.⁸

History has shown that pharmaceuticals can dramatically improve population health despite their “downstream” approach to prevention and treatment. Both vaccines and antibiotics have considerably reduced the burden of infectious disease worldwide but are not in opposition to a population health approach that improves living conditions and sanitation. Medical interventions, including statins, have been an important tool for lowering cardiovascular disease mortality at the population level, despite not targeting upstream causes of poor diet. But for pharmaceutical interventions to reach their public health potential, they must be widely accessible. The introduction of new medical technologies can increase health inequalities if the more advantaged can access these breakthroughs sooner or more easily, as is already the case with GLP-1 treatments.⁹ Besides prevention and attention to structural determinants, ensuring equitable access to current and future medical treatments for obesity will be an important role of public health. Recent estimates suggest that, if all eligible US adults received GLP-1 drugs at current discounted prices ($6,500 per year), the annual aggregate cost would be equal to all other US prescription drug spending combined.⁸ Given the large socioeconomic and racial/ethnic differences in obesity and related chronic diseases, the current high prices for these drugs will exclude those who need and could benefit the most. With many more drugs in this class under development, the price is likely to drop and quality to improve over time.¹⁰ Ensuring broad and equitable access will require cooperation across many groups, including drug manufacturers, health care providers, and policymakers. Public health advocacy should take a leading role in this endeavor.

Obesity is a population-level problem, and we shouldn’t give up on existing public health efforts to reduce it. But public health needs help. Anti-obesity drugs are a potential game changer not only for individuals suffering from diabetes and other complications but also for reversing troubling mortality trends in the US population. Like any new technology, these drugs may have both anticipated and unanticipated downsides, and we should be vigilant in monitoring both the short- and longer-term impacts of these medications. Despite the many uncertainties, we encourage public health to work in collaboration and not in opposition to these promising new tools. Population health scientists are well placed to study how these tools may interact with the broader social determinants shaping obesity and health trends across the life course in both expected and unexpected ways. We should not give up on upstream structural determinants of obesity, but we also should welcome extremely effective downstream interventions that can save lives.

References:

1. Fryar, C., Carroll, M. & Afful, J. Prevalence of Overweight, Obesity, and Severe Obesity among Adults Aged 20 and over: United States, 1960–1962 through 2017–2018. https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/overweight-obesity-adults-H.pdf (2020).
2. Preston, S. H., Vierboom, Y. C. & Stokes, A. The role of obesity in exceptionally slow US mortality improvement. PNAS 115, 957–961 (2018).
3. Davies, M. et al. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA 318, 1460–1470 (2017).
4. Ryan, D. H. et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med 30, 2049–2057 (2024).
5. Drucker, D. J. The benefits of GLP-1 drugs beyond obesity. Science 385, 258–260 (2024).
6. Olshansky, S. J. et al. A potential decline in life expectancy in the United States in the 21st century. N. Engl. J. Med. 352, 1138–1145 (2005).
7. Mehta, N. K., Abrams, L. R. & Myrskylä, M. US life expectancy stalls due to cardiovascular disease, not drug deaths. PNAS 117, 6998–7000 (2020).
8. Mozaffarian, D. GLP-1 Agonists for Obesity-A New Recipe for Success? JAMA 331, 1007–1008 (2024).
9. Chang, V. W. & Lauderdale, D. S. Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins. J Health Soc Behav 50, 245–260 (2009).
10. Sidik, S. Beyond Ozempic: brand-new obesity drugs will be cheaper and more effective. Nature 619, 19–19 (2023).

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