Q&A: Weight-loss drugs may help patients ‘catch up’ if behavioral therapy fails

Key takeaways:

• Phentermine greatly helped patients who responded poorly to a behavioral intervention lose weight.
• A researcher underlined that a healthy lifestyle is still crucial “even in the context of other treatments.”

Adding an anti-obesity medication alongside behavioral therapy produced significantly more weight loss in patients who initially struggled with the therapy, a study in Nature Medicine showed.

“Early intervention is crucial because patients who don't see initial results are more likely to become discouraged and discontinue treatment altogether,” Jena Shaw Tronieri, PhD, a senior research investigator at the University of Pennsylvania Perelman School of Medicine Center for Weight and Eating Disorders, said in a press release.

The use of weight loss medications like GLP-1 receptor agonists has continued to trend upwards, especially in people without diabetes. A study recently published in Annals of Internal Medicine showed that GLP-1 use in people without diabetes increased from 0.1% to 0.4% from 2018 to 2022, reaching nearly $6 billion in annual national expenditures.

In the current double-blind, randomized controlled trial, Tronieri and colleagues assessed the effect of prescribing weight-loss medications to people who lost less than 2% of their starting weight after a month of weekly behavioral sessions.

These participants were given either phentermine or placebo alongside their continued behavioral sessions.

Tronieri and colleagues reported that participants who took placebo along with the sessions lost only 2.8% of their starting weight after 24 weeks of treatment.

In comparison, participants given phentermine to go alongside the sessions reduced their starting weight by 5.9% during the same period.

Participants who responded well to the behavioral intervention continued without weight loss treatment and lost 5.1% of their starting weight over the 6 months.

Tronieri spoke with Healio to discuss the findings, how early providers could start patients on anti-obesity medications if behavioral treatment fails and more.

Healio: What led you to conduct the study? Was there anything notable about the data?

Tronieri: We’ve known for a long time that patients who do not respond well in the early parts of obesity treatments don’t tend to catch up later on. Early weight loss is a very strong predicator of later weight loss. But we haven’t had a really good grasp on what to do about it.

I think that this study is important in demonstrating that when treatment is changed at that time, patients actually can catch up to where the early strong responders arrive at in weight loss, whereas on average most people do not if they just continue with that same treatment.

Healio: How early could anti-obesity medications be introduced if behavioral interventions fail?

Tronieri: We used 4 weeks because we had seen in the literature that by that point, you can distinguish people who are likely to have a good response from people who aren’t. We do see differences even earlier — if you look in our study, even at week 2, you can see that individuals who were classified as early nonresponders are different in weight loss than those who tend to respond strongly later in treatment. But we haven’t really tested earlier cutoffs in terms of how well they classify people’s later progress.

In this research we had to choose a single timepoint, but in clinical practice, it might be important to have that conversation in an ongoing way and check in with patients at multiple different time points to see whether they’re on track and whether they continue to be on track. While it’s rarer, we do see some people who start strong but struggle later in treatment, and a minority of early nonresponders do achieve a significant weight loss. For example, 25% of the patients assigned to placebo did lose more than 5% of their starting weight in our study. In clinical practice, a patient might choose to try behavioral methods for longer, particularly if they can identify situational factors or additional behavioral changes that they can make that are likely to improve their trajectory.

Healio: Should lifestyle changes still be the first approach to overweight and obesity?

Tronieri: We generally believe that a healthy lifestyle remains important even in the context of other treatments. Even when patients are being provided with anti-obesity medication from the start, support and/or education to make sure that they are losing weight in a healthful way remains important and may benefit other health outcomes.

Lifestyle modification can make sense as a first approach because it is effective on average for improving weight and health and generally has fewer risks than medical treatments like anti-obesity medication. However, access to evidence-based programs is not always good, and decisions about which treatment should be started first are also going to depend on factors like other medical conditions that the patient might have or if there’s a pressing need for larger and more immediate weight loss. For example, I have worked with patients who were waitlisted for receiving a transplant due to body weight, and if you’re awaiting a lifesaving treatment, you would want to start with the weight loss method most likely to produce the fastest results that is also safe for that patient’s medical conditions.

Overall, there are going to be a number of different factors that would influence a provider’s decision about which treatment to recommend, not to ignore patient preferences. Not all patients wish to try anti-obesity medications, and not all patients feel like lifestyle modification treatment is going to be beneficial in comparison to what they have already tried on their own.

Healio: Where does research on the effectiveness of anti-obesity medications used in this context go from here?

Tronieri: One important question is whether it’s beneficial to continue to provide early nonresponders with behavioral counseling sessions after introducing a medication, or if the initial period of behavioral treatment is enough for the patient to get an understanding of lifestyle changes and then proceed successfully with medication treatment and no or minimal counseling. Behavioral treatment can improve average weight loss with certain anti-obesity medications, but patients who didn’t benefit from the first month of counseling may not see much benefit with combined treatment above medication alone. I think that needs to be compared because behavioral treatments are provider-intensive and labor-intensive for the patient to attend as well.

We also need to see what the effectiveness of other medications are in the patient population who responds minimally to behavioral treatment, and, in the future, whether there is even a way to match the reasons that a patient struggled with behavioral weight loss to the selection of which type of medication would be the best fit. Given that these medications have slightly different mechanisms or ways that they work, one might be better suited to some patients over others.

References:

• Anti-obesity medication boosts weight loss when behavioral therapy falls short. Available at: https://www.pennmedicine.org/news/news-releases/2025/march/early-anti-obesity-medications-boost-weight-loss. Published March 18, 2025. Accessed March 24, 2025.
• Shadbolt C, et al. Ann Intern Med. 2025;doi:10.7326/ANNALS-24-02878.
• Tronieri JS, et al. Nat Med. 2025;doi:10.1038/s41591-025-03556-3.

For more information:

Jena Shaw Tronieri, PhD, a senior research investigator at the University of Pennsylvania Perelman School of Medicine Center for Weight and Eating Disorders, can be reached at primarycare@healio.com.