Key Points:
- GLP-1 weight-loss drugs – Patient traits like muscle stiffness or osteoarthritis influence response.
- Response varies by drug – 12.5% super responders, 35% moderate, 47% minimal; newer drugs show better outcomes.
- Personalized treatment next – AI algorithms may help match patients to the most effective medication.
U.S. researchers have identified clinical patterns that may help determine which patients respond best to GLP-1 weight-loss drugs such as Wegovy and Zepbound, according to findings published online ahead of peer review on Nov. 19. The analysis suggests that patient health characteristics before treatment may guide physicians in selecting the most effective medication.
Early Response Patterns
The research team, led by Venky Soundararajan of the Massachusetts-based data company conference, reviewed 14 million doctors’ notes and 15 million clinical entries from more than 135,000 patients. Each patient had taken only one GLP-1 weight-loss drugs. The data showed that roughly 12.5% of patients qualified as “super responders,” losing more than 15% of their body weight within a year of starting treatment.
Another 35% of patients were moderate responders, losing between 5% and 15%. Nearly half, or 47%, fell into the minimal-response category, losing less than 5%. An additional 5% initially lost about 5% of their weight but regained it within a year.
“The trajectories of weight loss were very diverse,” Soundararajan said. “If I am a clinician seeing patients, I need to know what medicine will best benefit my patient. I also need to know what benefits and what side effects they are likely to have.”
Drug-by-Drug Differences
The analysis found differences across specific brands. With Eli Lilly’s Zepbound and Mounjaro, 23% to 28% of patients were minimal responders. For Novo Nordisk’s Wegovy and Ozempic, the share ranged from 30% to 43%. Earlier-generation drugs such as Trulicity, Saxenda, and Victoza showed minimal-response rates of 46% to 63%.
According to the researchers, newer GLP-1 weight-loss drugs appear to reduce the proportion of patients who experience limited weight loss, though overall results still vary widely across individuals.
Medical Conditions Analyzed
The team used artificial intelligence tools to evaluate the presence or absence of 1,300 medical conditions before and after patients began treatment. The pre-treatment presence of muscle stiffness without knee pain or osteoarthritis increased the likelihood that a patient prescribed Zepbound would become a super responder.
That pattern suggests that patients with obesity-related muscular dysfunction but preserved joint health may be especially likely to achieve significant results with tirzepatide, the active ingredient in Zepbound and Mounjaro
Soundararajan said patients with knee pain, osteoarthritis, chest pain, sleep apnea, or fibromyalgia were less likely to be strong responders to Zepbound.
Condition-Specific Outcomes
The analysis also identified conditions associated with favorable outcomes for other drugs. Patients with sciatica saw improvements when treated with Wegovy. Pre-existing melanoma appeared to correlate with stronger responses to Wegovy, while patients with actinic keratosis were more likely to respond well to Mounjaro. Those with aged osteoporosis were more likely to show strong weight-loss results with Ozempic.
Across all GLP-1 weight-loss drugs, patients with sinus pressure before treatment reported improvements afterward.
Next Steps for Personalized Treatment
The researchers said the next phase of their work involves developing an algorithm that assigns benefit-risk scores for different GLP-1 drugs based on individual patient characteristics. That tool would require testing in prospective studies.
“These signals will continue to get more and more refined as data is collected from more and more patients,” Soundararajan said.
The findings come as use of GLP-1 medications expands across the United States, driven in part by recent price cuts that have made the drugs more accessible. While millions have begun treatment, physicians and researchers continue to study why responses vary widely and how to match patients with the GLP-1 weight-loss drugs most likely to provide effective, sustained weight loss.
