Early use of anti-obesity medication more than doubles weight loss
Incorporating an anti-obesity medication just one month after beginning behavioural therapy—rather than the current guideline of waiting six months—can more than double weight loss for individuals who initially struggle with lifestyle changes alone. This is the key finding of a new study from researchers at the Perelman School of Medicine at the University of Pennsylvania, published in Nature Medicine.
Obesity and Its Health Implications
Obesity affects over 40 percent of adults in the United States and is associated with a heightened risk of heart disease, stroke, type 2 diabetes, and certain cancers. Behavioural therapy—also referred to as lifestyle intervention—along with anti-obesity medication, are recognised as effective strategies to support individuals in achieving their weight and health-related goals. However, the effectiveness of these approaches can vary widely among individuals. This study addresses a significant gap in obesity management by demonstrating that those who struggle with one form of treatment may benefit substantially from the timely addition of another.
Most obesity management guidelines recommend an initial six-month period of lifestyle intervention before considering medication. These lifestyle modifications typically involve reducing calorie intake, increasing physical activity, and employing behavioural strategies such as tracking food consumption and exercise. These interventions are often delivered through structured counselling sessions, where trained professionals help participants set realistic goals and provide accountability. However, research indicates that up to 50 percent of individuals undertaking lifestyle interventions alone do not achieve a clinically meaningful weight loss of at least five percent of their starting weight.
Dr Jena Shaw Tronieri, Senior Research Investigator at the Center for Weight and Eating Disorders in the Department of Psychiatry at the University of Pennsylvania, noted the critical lack of research into next steps for individuals who do not respond adequately to behavioural therapy alone:
“Surprisingly little is known about how to help patients who struggle to lose weight when they are already receiving frequent lifestyle counselling sessions. Some experts have suggested that adding an anti-obesity medication should be the next step, but no studies have tested whether this approach actually improves weight loss.”
Early Intervention Leads to Greater Weight Loss
The research team, led by Tronieri, assessed an early intervention approach by identifying individuals who had lost less than two percent of their initial body weight after four weeks of weekly behavioural sessions (equating to less than one pound per week for most participants). These individuals were then randomly assigned to receive either the anti-obesity medication phentermine hydrochloride (15.0 mg per day) or a placebo while continuing with 24 additional weeks of behavioural intervention.
Phentermine, an appetite suppressant, is the longest-approved weight-loss medication currently available, having received U.S. Food and Drug Administration (FDA) approval in 1959.
The results demonstrated a significant disparity in weight loss outcomes:
- Participants who received only the placebo alongside behavioural counselling lost an average of 2.8 percent of their initial weight over the 24-week period.
- In contrast, those who received phentermine experienced a weight loss of 5.9 percent—more than double the amount lost by the placebo group.
For context, an individual weighing 250 pounds (approximately 113 kg) at the study’s outset would have lost around 15 pounds (6.8 kg) with the medication, compared to roughly 7 pounds (3.2 kg) with behavioural therapy alone.
Meanwhile, individuals who were “early strong responders”—those who had already achieved notable weight loss in the first month—continued with lifestyle interventions alone and achieved an additional 5.1 percent reduction in their initial weight over the same six-month period.
Implications for Obesity Treatment
Dr Tronieri emphasised the importance of adapting obesity treatment strategies to prevent disengagement and improve patient outcomes:
“Our results strongly support the addition of anti-obesity medications for patients who do not achieve meaningful weight loss with behavioural methods alone. They also suggest that the medication can be introduced early in treatment, rather than waiting until a patient completes a full six-month programme. Early intervention is crucial because patients who don’t see initial results are more likely to become discouraged and discontinue treatment altogether.”
The study’s findings offer a potential framework for healthcare professionals supporting individuals who find it challenging to lose weight through lifestyle changes alone. While this study focused on phentermine, researchers caution that additional trials are necessary to determine whether newer FDA-approved medications, such as semaglutide or tirzepatide, could yield even greater improvements.
Study co-author Dr Thomas A. Wadden, Professor of Psychology in Psychiatry, noted:
“If the people who were early non-responders took one of the newer approved medications, like semaglutide or tirzepatide, it’s likely they could easily double or triple their weight loss compared to phentermine. Additional research is needed to confirm this hypothesis.”
Future Research Directions
The study was funded by the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116935). Researchers aim to build upon these findings by exploring the effectiveness of alternative medications and refining treatment protocols to maximise weight loss outcomes for those who do not respond to behavioural interventions alone.
This study represents a significant step towards more personalised obesity management, with early introduction of medication offering a promising approach for individuals who find it difficult to achieve weight loss through lifestyle modifications alone.
