The improvement in pain, Dr. Bliddal says, suggests that semaglutide was considerably more effective for this patient group than standard, over-the-counter painkillers, at least by the end of the trial period. To participate in the trial, patients had to have a pain score of at least 40 on the WOMAC scale. With an average starting score of 72.8 for those assigned to the semaglutide arm, the major improvement after 68 weeks (by nearly 42 points, on average) would have knocked many of those participants out of eligibility. “If they had presented with the pain story that they ended up with, we would not have put them in the trial,” he says.
The observed incidence of adverse events, most commonly gastrointestinal disorders, was fairly low for both groups. Such events prompted 6.7% of participants in the semaglutide group and 3.0% in the placebo group to drop out of the trial; Dr. Bliddal says neither is a significant concern.
“We have learned how to use semaglutide and you have to start slow,” he says. “You have to increase the dose over a certain number of weeks to avoid most of this gastrointestinal trouble, and this works.” A bigger hurdle might be availability: The drug’s surging popularity for treating other weight-related conditions has led to shortages in some markets.
Another caveat is the well-known rebound effect in which patients who stop taking semaglutide can quickly regain lost weight. “There are two ways out of this,” Dr. Bliddal says. One is to gradually taper the drug dosage over time, paired with individual telephone or group-based support by providers to help ease the transition. The other is to provide patients who stop taking the drug with regular dietary consultations, preferably in supportive group settings.
Commentary
Two outside experts praised the STEP 9 trial’s design and methodology and agreed that its findings support the pivotal role of weight loss in improving patients’ pain and function, but urged caution given the absence of long-term data.
“The clinically meaningful improvements observed in the placebo group highlight the importance of structured counseling on diet and physical activity as foundational components of care,” says Zubeyir Salis, PhD, a public health researcher at the Centre for Big Data Research in Health at the University of New South Wales, Sydney. Regarding the study’s “compelling” results, he adds, “Semaglutide represents a promising pharmacological adjunct that may enhance these benefits, particularly for patients struggling to achieve sufficient weight loss through lifestyle changes alone.”
