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Study to analyse the real-world effectiveness of GLP-1 weight-loss drugs and inequities in access to these medications

The Robert Wood Johnson Foundation has awarded a grant to Andrew Stokes, associate professor of global health, Boston University School of Public Health, to analyse the real-world effectiveness of glucagon-like peptide-1 (GLP-1) receptor agonists and inequities in access to these medications.

Andrew Stokes

“GLP-1 receptor agonists could be transformative for populations disproportionately affected by obesity,” says Stokes, principal investigator of the grant. “However, what we know so far is that the greatest utilization of these therapies have been observed in predominantly wealthy communities, which have comparatively lower rates of obesity and associated cardiometabolic conditions.”

Most of the data on these therapies thus far has been driven by clinical trials, which do not account for disruptions in medication adherence that often occur among everyday people.

Stokes and a team of researchers from the School of Public Health will seek clarity on the population health effects of GLP-1 drugs with a new grant from the Robert Wood Johnson Foundation. The three-year, $500,000 award will support research that will examine the effects of GLP-1 medication use on obesity care, health disparities, and population health outcomes in the US.

“In a clinical trial, people receiving the treatment are able to adhere to the prescribed regimen through support from study staff and incentives for participation, whereas in a real-world setting people may experience side effects or lose insurance coverage and stop taking their medications,” explained Stokes. “We hope to learn whether the health benefits observed in clinical trials will translate into real-world settings and diverse subpopulations.”

Originally developed to treat diabetes, GLP-1 receptor agonists help reduce food intake by mimicking a hormone that suppresses appetite. GLP-1 receptors can be found in many locations in the body, including the gut, brain, and heart. While the first drug in this class, exenatide (Byetta), was approved by the FDA in 2005, more recent drugs like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) outperform the older drugs in the class and other anti-obesity medications. Recent clinical trials have also demonstrated that Ozempic and Wegovy are highly efficacious in preventing adverse cardiovascular events like heart attacks.

This class of drugs is challenging outdated beliefs that obesity is an issue of individual behavior and willpower. Obesity is a chronic disease exacerbated by a complex array of biological, social, environmental, and structural forces. These influences include geographic factors like access to healthy food, green space, and healthcare, as well as socioeconomic status, chronic stress, discrimination, and environmental pollution.

“What’s so unique about these drugs is that they directly target the biological drivers underpinning obesity,” added Meghan Podolsky, research fellow in the Department of Global Health (GH) and MS student in epidemiology, who is working on the project. “Essentially, they enable people living with obesity to better resist the external influences that can cause weight gain.”

The research team also includes alum Rafeya Raquib (SPH’22), research fellow in GH.

This new grant is the latest project in nearly 15 years of research by Stokes and colleagues on the health consequences of obesity and disparities in access to obesity-related healthcare in the U.S. A 2011 study in the American Journal of Public Health found that obesity reduced US life expectancy at age 50 by 1.54 years for women and 1.85 years for men. Subsequent studies in the journals PNAS and JAMA Network Open—the latter of which was conducted using data from the Framingham Heart Study at BU—found links between higher body mass index and increased mortality risk, including the cumulative effects of weight status over multiple decades.

“By reconstructing weight history, we have shown that the risks of overweight and obesity are greater than commonly appreciated,” Stokes says.

Despite the health benefits of weight-loss interventions like nutritional counselling, bariatric surgery, and medications like GLP-1 receptor agonists, utilisation of obesity-related healthcare remains extremely low, especially by populations that are most affected by obesity. The disconnect between the population prevalence of obesity and care utilization is driven by a range of factors such as stigma and discrimination in healthcare settings, lack of educational and cultural training among physicians on how to address this issue with patients, and the cost of treatment.

The new GLP-1 receptor agonists can cost around $1,000 per month without insurance, and coverage can vary by source of insurance. Medicare and Medicaid are prohibited from covering any drugs for weight-loss indications, but may cover the new drugs for individuals with diabetes or cardiovascular disease.

The researchers said this body of evidence increases the need to study GLP-1 drugs as a potential approach to addressing persistent obesity in the US, which currently affects about 42 percent of the US population, with higher rates among Black, Hispanic, and American Indian/Alaska Native adults, according to the Centers for Disease Control and Prevention.

The team will study the effects of GLP-1 drugs on five disproportionately burdened populations: racially minoritised groups, individuals of low socioeconomic status, rural and non-metro populations, people living with disabilities, and sexual and gender minorities. They will utilise real-world electronic health records, machine learning, and other novel methods to investigate changes in obesity-related healthcare usage before and after the emergence of these medications, as well as identify predictors of GLP-1-assisted weight loss, the drugs’ effectiveness by subpopulation, and how these rapidly evolving therapies may influence future life expectancy based on policy changes that address the existing disparities in access and use.


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