Filling evidence gaps on obesity treatment

Several new grants will fund research on the effectiveness, safety, and equitable use of anti-obesity medications

Researchers at Kaiser Permanente Washington Health Research Institute (KPWHRI) have led and contributed to many studies looking at safe and effective ways to treat and prevent obesity. David Arterburn, MD, MPH, a senior investigator at KPWHRI, is beginning work soon on 3 new grants that will help clinicians and patients better understand the different treatment options, including newer anti-obesity medications that have only recently been approved by the Food and Drug Administration (FDA).

“Newer medications for obesity are very popular at the moment, and they do show promise for improving health outcomes,” Arterburn said. “But there’s a lack of evidence directly comparing these new pharmaceutical options with older medications, for example, or with other treatment options that exist. Having more knowledge is really important so that people can make informed decisions and fully understand the risks as well as the potential benefits of the different choices that are available.”

Many of the existing trials for new anti-obesity medications such as Ozempic and Wegovy look at weight loss as the primary outcome, he explained, but weight loss isn’t itself always an indication of better health. Two of the new grants will fund a deeper look at health outcomes like cardiovascular health and reduced complications from diabetes, while a third will focus on building a roadmap for equitable access to these medications.      

Understanding effectiveness and safety of different treatment options

A $2.7 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will allow Arterburn and colleagues to compare bariatric surgery and medication treatment for people living with both type 2 diabetes and obesity. The researchers will compare the effectiveness and safety of these options, which treat obesity and type 2 diabetes by promoting weight loss and lowering glucose levels.

People living with both these conditions are in one of the highest-risk groups for complications that affect the circulatory system, which can include narrowed blood vessels, blood clots, and damage to the eyes or nerves. Both bariatric surgery and medications can reduce this risk, but there is a lack of evidence comparing the risks and benefits of these options head-to-head. The study findings will help clinicians and patients make evidence-based decisions about a course of treatment.

The 4-year project will be the largest and longest study to date to look at these different treatment options. The researchers plan to analyze outcomes such as blood pressure, glucose control, and reduction in complications from diabetes over 5 years of follow-up. They will also look at rates of hospitalization during and after treatment. Using data from the electronic health record for a diverse cohort of patients nationwide, the research will provide important information not only about the different treatments but also about how their impact might vary across demographics.

“Our previous work has shown that the benefits and risks of bariatric surgery are different for patients depending on the severity of their diabetes, other health conditions they might have, and their age, race, and ethnicity. So, it’s very important for us to have data from a large and diverse population for this study,” Arterburn said.

Equitable use of anti-obesity medications

Another $2.7 million grant from the NIDDK is funding a project looking at how to reduce disparities in access to anti-obesity medications and how best to ensure that they are prescribed to people with the greatest clinical need.

New anti-obesity medications are becoming a widely used treatment option, but there are no clear guidelines for how to best make them available in an equitable way. Some evidence suggests that only 1% to 3% of all patients who are eligible for these medications actually get them. Cost is one barrier, but others include concerns about medication safety, a lack of evidence about their long-term effects, and limited time for patients to talk about this treatment option with their doctor.

Arterburn is one of several principal investigators on the new project, which will support work to identify barriers and facilitators for use of anti-obesity medications and provide targeted strategies for equitable access to these treatments. By gathering data from clinics in 3 different health systems, the researchers hope to find out what factors lead to patients receiving prescriptions and continuing to take these medications. They plan to conduct patient interviews and look at patient and clinician attitudes toward anti-obesity medications. They will also analyze what regional and national health care insurers and employers think about the clinical and economic evidence for these treatments, and how that may impact coverage.

The long-term goal of this 5-year project is to design and test interventions to increase equitable use of anti-obesity medication, leading to templates that can be used by other health systems.

Comparing outcomes and use of different medications

Arterburn is also a principal investigator on a 5-year, $3.8 million grant from the National Heart, Lung, and Blood Institute that will fund work to compare health outcomes, utilization, and cost of care for all anti-obesity medications.

In total, the researchers will compare 6 different types of anti-obesity medications used to treat patients with type 2 diabetes, hypertension, or dyslipidemia (elevated cholesterol or fats in the blood). They will use insurance claims data to look at use of health care services, health care costs, and health outcomes such as improvements in diabetes markers, blood pressure, or cholesterol, or reductions in cardiovascular events like stroke, heart failure, or arrythmia.

The project will be the first nationwide study to compare health and health-service outcomes for several of the newer anti-obesity medications that were recently approved by the FDA. These include semaglutide, a medication that mimics a hormone in the body called GLP-1 that has a role in insulin production and signaling fullness (this is the active ingredient in Ozempic and Wegovy). The oldest medication, phentermine, was approved for use in 1959, and the newest, tirzepatide, in 2023.

 “We have major evidence gaps when it comes to understanding how the different medications stack up against each other,” Arterburn said. “Different drugs have different mechanisms of action, so the risks and outcomes are likely to vary across patients. Our hope is that this study can address some of those gaps and add to the evidence base so that patients and clinicians have good information to rely on when making informed decisions.”

By Amelia Apfel