Moving the conversation about obesity beyond the scale

Every so often, the conversations that people in health care have become so pervasive that they dominate the zeitgeist, intersecting with mainstream media and popular culture. Oprah Winfrey’s recent ABC special “Shame, Blame, and the Weight Loss Revolution” is a good example of this. Now streaming on Hulu, the broadcast garnered widespread attention, including coverage from People Magazine and The New York Times. Oprah delved into her personal struggles with weight, placing her narrative against the broader backdrop of societal views on obesity. It’s a journey many people have shared with Oprah since “The Oprah Winfrey Show” began in the mid-1980s.

However, the special also illustrates the provocative nature of the discourse on obesity and highlights the societal shift in addressing obesity.

The public discussion on obesity and weight loss, particularly concerning GLP-1 receptor agonists — the technical name for drugs like Wegovy (semaglutide) and Zepbound (tirzepatide) — is evolving quickly. The introduction of these new medicines is contributing to the public’s acceptance of obesity as a disease rather than a lifestyle choice — finally catching up with what clinicians and others have been saying for years.

The National Institutes of Health identified obesity as a disease in 1998. The American Obesity Society did so in 2008 and was eventually followed by the American Medical Association in 2013.

The media’s fascination with “Ozempic face” underscores a more surface-level engagement, prioritizing conversations on aesthetic concerns over the substantive health implications of obesity treatments and quality weight loss.

For drug developers like me, the shift from viewing obesity as a personal fault to seeing it as a disease that is sometimes best served by treatment with a medication validates and supports the work we do. But it’s time to move the focus beyond weight to the consequential effects that obesity medications may have on body composition. It’s an important topic that isn’t much discussed in the public domain.

The human body can be thought of as having two types of mass: lean mass is made up of muscles, bones, various organs, and water; fat mass, also known as stored fat, is used as energy for the body. A debate over which type of mass obesity medications affect and what that means for long-term health is just beginning to unfold.

The loss of fat mass is responsible for the beneficial long-term health outcomes associated with obesity treatments. Over time, loss of lean mass can contribute to progressive frailty, particularly in older people.

This topic has sparked a diversified approach to companies’ weight loss portfolios, as captured by STAT’s Obesity Drug Tracker, which reflects differing views on the optimal approach to weight loss treatments. Currently available GLP-1s were not explicitly designed to preserve lean muscle mass as part of the weight loss process. Emerging biotechs, including BioHaven and our team at CinFina Pharma, are working to achieve weight loss while maintaining or enhancing lean muscle mass and preserving energy expenditure.

I find worrisome clinical findings, such as those from the STEP-1 trial for semaglutide, which revealed that around 40% of weight loss could involve lean mass, potentially affecting metabolic health and decreasing the body’s energy expenditure. To me, a weight loss approach that prioritizes preserving lean mass and energy expenditure will be better for its potential to support durable, sustainable, quality weight reduction as well as long-term health and metabolic stability.

There are certainly people who believe that I and others are barking up the wrong tree, as I know from my conversations with experts in the field, some of whom expressed skepticism in a recent STAT article about the necessity of preserving lean mass during weight loss. They may be right; I may be right. Science will give us answers, but science works by including diverse perspectives.

As scientists and experts strive to redefine standards for weight loss treatments, obesity drug developers should incorporate lean mass and metabolic measurements in their clinical trial designs. This approach will ensure a holistic view of weight loss that prioritizes not only the reduction of body weight but also the maintenance of metabolic health and physical functionality — information that can answer how important the preservation of lean mass is in weight loss.

Millions of Americans struggling with obesity need ways to lose weight that decrease related comorbidities and benefit the body as a whole. Including measures of preserving lean body mass in clinical trials can help achieve those goals.

Jonathan Isaacsohn, M.D., is a cardiologist and the CEO of CinRx Pharma.