Adding anti-obesity medication just one month into behavioral therapy—rather than waiting the standard six months—can more than double weight loss for individuals struggling with lifestyle changes alone, according to a new study published in Nature Medicine by researchers from the Perelman School of Medicine at the University of Pennsylvania.
The Challenge of Obesity and Weight Management
Obesity affects over 40% of American adults and significantly increases the risk of heart disease, stroke, type 2 diabetes, and certain cancers. Behavioral therapy, often called lifestyle intervention, along with anti-obesity medications, can help individuals reach weight and health goals. However, success varies widely among individuals, and many struggle to achieve meaningful weight loss through behavioral changes alone. This study bridges a crucial gap by showing that early intervention with medication can enhance weight loss outcomes for those who do not respond to initial lifestyle interventions.
Rethinking Traditional Guidelines
Current obesity management guidelines recommend at least six months of behavioral interventions—including calorie reduction, increased physical activity, and structured counseling—as the first step for individuals needing weight loss support. These interventions provide accountability, goal-setting strategies, and professional feedback. However, research indicates that nearly half of participants fail to lose at least 5% of their starting weight through lifestyle changes alone.
Until now, there has been limited research on how to help patients who do not respond to behavioral counseling. While some experts have suggested adding anti-obesity medication, there has been little direct evidence supporting its effectiveness in these cases.
Accelerating Weight Loss with Early Medication
The new study, led by Jena Shaw Tronieri, PhD, explored whether introducing medication earlier in treatment could benefit those struggling with weight loss. Participants who had lost less than 2% of their body weight after one month of weekly behavioral sessions (equating to less than 1 pound per week for most) were randomly assigned to take either the appetite suppressant phentermine hydrochloride (15.0 mg per day) or a placebo for 24 additional weeks while continuing behavioral intervention. Phentermine, the oldest FDA-approved weight loss drug, has been in use since 1959.
Results showed that participants receiving the placebo lost only 2.8% of their initial weight over the 24-week period. However, those who added phentermine more than doubled their weight loss, reaching 5.9% of their starting weight. For perspective, a 250-pound individual would lose approximately 15 pounds with medication, compared to only 7 pounds with behavioral therapy alone. Meanwhile, participants who initially responded well to behavioral therapy—labeled as “early strong responders”—continued without medication and lost an additional 5.1% of their starting weight.
A New Approach to Sustainable Weight Loss
“Our findings strongly support adding anti-obesity medication for patients who do not achieve significant weight loss through behavioral therapy alone,” said Tronieri. “Moreover, they suggest that medication can be introduced early in treatment rather than waiting until after six months. Early intervention is key because patients who see little progress early on are more likely to become discouraged and discontinue treatment.”
The study provides a potential roadmap for healthcare professionals seeking more effective strategies for patients struggling with weight loss. However, further research is needed to determine whether newer FDA-approved weight-loss medications, such as semaglutide or tirzepatide, might yield even better results.
“If early non-responders took one of the newer medications, it’s likely they could double or triple their weight loss compared to phentermine,” noted study co-author Thomas A. Wadden, PhD, a professor of Psychology in Psychiatry. “Future studies should explore this possibility.”
This research reinforces the importance of a personalized approach to weight management, ensuring that those who struggle with lifestyle interventions alone have additional options to achieve lasting, meaningful weight loss.
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