Obesity medications such as semaglutide and tirzepatide are fueling unprecedented weight loss for many patients as well as improving chronic obesity-associated conditions such as diabetes, fatty liver disease, and cardiovascular risks.

“If these medications are so effective, why do we need to bother with lifestyle changes? Why can’t we just set the drug dose, give patients the prescription, and then just let them go?,” Ariana Chao, PhD, director of research, Johns Hopkins Healthful Eating Activity and Weight Program, Baltimore, posed those questions somewhat rhetorically in her presentation at Obesity Week 2025 in Atlanta.

Removing lifestyle changes “is a tantalizing thought to some — but not so fast,” she told the audience. The key components of lifestyle modification — diet, physical activity, and behavior change — have been the foundation of obesity treatment for generations, such that the image representing obesity management traditionally has been a pyramid, with lifestyle modification at the base, and pharmacotherapy, devices, and surgery piled on top.

But in recent years, a new picture has emerged. Instead of underlying obesity management, lifestyle modification is now considered a core pillar of obesity treatment, similar to what the Obesity Medicine Association uses, and those medications have a pillar of their own, on a par, with surgery and devices.

Yet the reality is, even intensive lifestyle interventions — generally defined as 14 or more clinic visits in the first 6 months of treatment, then monthly visits for maintenance — can only go so far. Most often, they tend to produce less weight loss than patients are seeking, Chao said. By contrast, the new medications “can help us get us closer to what the patient’s goals are and are associated with greater health benefits.”

“Lifestyle change can be important in modifying the external obesogenic environment individuals are living in, and obesity management medications can be helpful in terms of modifying the internal or biology underlying obesity,” she explained. “We often like to pit treatments against one another, but I believe the future of obesity care isn’t an ‘either/or’; It’s a ‘both,’ especially when it comes to being able to treat patients holistically, long-term, and in a sustainable way.” 

Why and How to Put Lifestyle Change and Drugs Together

There are a number of reasons to integrate lifestyle changes with obesity medication, Chao said. “One hypothesis is that medication can help facilitate adherence to lifestyle modifications. When biology is quieted and food noise decreases, there might be opportunities to retrain lifestyle habits. When individuals don’t have as much adiposity, they might be able to move more easily to exercise.” 

The “additive” hypothesis posits that each treatment might target unique variables, leading to better outcomes, while the “synergistic” hypothesis suggests that the treatments enhance each other’s efficacy when implemented together.

The “compensatory effect” hypothesis postulates that lifestyle interventions might help mitigate some of the adverse events that may occur with some of the obesity management medications.

There are few trials demonstrating the efficacy and safety of these strategies, Chao said, “but some experts offer suggestions on what can be done now to help our patients, before we have evidence from randomized controlled trials.”

For example, combining medication and lifestyle interventions simultaneously “can be implemented with low- and moderate-intensity lifestyle interventions (one or fewer contacts with the patient per month) or the higher intensity lifestyle interventions, where the contacts are much more frequent” to try to improve outcomes.

Sequencing the interventions is a strategy that could be used to help break through plateaus or improve maintenance, Chao suggested. “This has typically taken the form of engaging the patient in high-intensity lifestyle interventions and then switching to medication, perhaps to increase the durability of the effects or induce additional weight loss.” 

‘Rebuilding the Plane While Flying It’

Research is needed to compare not only the effectiveness of various strategies but also on specifics, such as counseling frequency when paired with the new medications, and whether more intensive counseling can mitigate some of the weight regain seen after discontinuation, Chao said.

For example, the lifestyle interventions in phase 3 trials of semaglutide and tirzepatide focused mainly on caloric reduction, either as a 500-calorie/d deficit or a reduced calorie diet, she said. A couple of the trials included individual healthy lifestyle counseling, seven provided macronutrient recommendations, and most recommended 150 minutes or more weekly of physical activity.

But overall, Chao said, “there’s not a ton of specificity in the recommendations, which is really important to consider as we enter the era of obesity treatment that includes medication, rather than behavioral obesity treatment alone.”

There’s also a need for evidence on strategies to foster implementation, she said. Primary care physicians are seeing more patients and sicker patients and have a lot on their plate. Therefore, “involving a multidisciplinary team with registered dietitians, obesity medicine specialists, psychiatrists, pharmacists, and clinical psychologists will be key to giving patients the best outcomes.” 

Right now, she said, “We’re rebuilding the plane while flying it. Everyone has different thoughts about what should be done and what sort of counseling we should provide to patients, and while some consensus is forming, much of it is based on expert opinions, without a lot of evidence or trials actually supporting them.”

Chao also emphasized that “knowing doesn’t equal doing.” If you simply tell patients to eat a certain amount of protein and exercise and do resistance training, they’re probably not going to do it, she said. “Lifestyle counseling, behavioral support, and helping people implement what we’re asking them to do is critical to holistically care for them. There is no medication right now that will compel someone to go to the gym or to eat healthy foods.”

“I view lifestyle modification as a phoenix rising from the ashes, with a shift from obesity being a lifestyle-change issue to a chronic disease with treatments that address biology,” she emphasized. “It’s not lifestyle or medications; it’s lifestyle and medication.”

Chao disclosed advisor relationships with Boehringer Ingelheim and Novo Nordisk and advisor and researcher relationships with Eli Lilly and Company.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.