MUSC helps lead international weight loss trial with promising results

Back in his office at the Medical University of South Carolina after speaking at the Endocrine Society’s annual meeting in Chicago, Patrick O’Neil chooses his words carefully. “This is just one study,” he says of the weight loss trial now being featured in news reports across the country. “I don’t want to oversell it.”

But there’s no doubt, he says, that the results of the study testing the drug semaglutide as a possible weight loss medication look promising. “In the high dose group, a little over a quarter of the participants lost at least 20 percent of their start weight. That’s nothing to sneeze at.”

O’Neil, along with obesity specialist John Wilding of the University of Liverpool in the United Kingdom, are leading the scientific reporting of the trial. It included 8 countries, 957 participants and 71 sites. It was sponsored by Novo Nordisk, the company that makes semaglutide.

Semaglutide, already approved at a different dosage for treating type 2 diabetes, is sold under the brand name Ozempic. O’Neil says he received no compensation for his role in the research. Funding for MUSC’s part of the trial went to the university.

The study testing semaglutide for weight loss was a phase 2 trial, meaning it was designed to be an initial test of whether the drug was safe and effective. It also compared different doses to see which, if any, worked best.

“We saw weight loss that was better than placebo in all doses,” O’Neil says. “In general, the higher the dose, the greater the weight loss.”

The participants in the year-long study, including 23 at MUSC, gave themselves daily subcutaneous injections without knowing if they were getting the drug being tested or an inactive placebo. The doses ranged from .05 milligrams of semaglutide a day to .4 milligrams. The participants were relatively healthy to begin with. They didn’t have diabetes and their blood pressure was under control. They just needed to lose weight.

The MUSC participants included 13 men and 10 women. Eleven are African-American and 12 are white.

As some of them learned, the drug treatment can have side effects. “With this medication, the most common adverse events are gastrointestinal,” O’Neil says. “What it’s doing is mimicking the effect of a peptide produced by the gut, so it’s not surprising you have GI effects. Of the GI effects, nausea is the most common. You can have some diarrhea or some constipation.”

O’Neil says the people who designed the trial knew that was possible and acted accordingly.

“From earlier trials, with these kinds of drugs, the decision was made by the sponsor based on experience to do a very slow dose escalation for people at anything other than the lowest dose.”

He says they found that the higher the dose, the higher the odds of GI trouble — to a point. “It tended to fall off after a time — the nausea. Moderate to severe nausea occurred very infrequently.”

All participants got lifestyle counseling at every visit, O’Neil says. “There was dietary and activity counseling and some behavior modification counseling for weight loss.”

He says the success of weight loss treatments tends to be measured by percentage of starting body weight lost. In this study, at the three highest dosages of semaglutide, between 75 and 80 percent of participants lost five percent or more of their starting weight. “That’s higher than you typically see. So we did some secondary analyses.”

In those analyses, the researchers found that between 11 and 27 percent of the people at the three highest doses lost at least 20 percent of their body weight. So a man who weighed 200 pounds would have dropped 40 pounds in a year, O’Neil says.

Phase 3 studies are in the works and MUSC will be recruiting participants, possibly in the late spring or summer, depending on Institutional Review Board approval. O’Neil says the researchers are writing up the results of the phase 2 study now for possible publication. He’s proud of the role MUSC is playing.

“It’s really rewarding and a privilege to be involved in the development of new treatments,” O’Neil says. “We didn’t invent this medicine, but by playing an active role in the evaluation of it, we are helping to determine its value for patients. This is another way the Weight Management Center has been recognized as contributing to more effective obesity treatments.”

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