Subcutaneous Semaglutide Trims Body Weight By 12% In Obese Patients Over 68 Weeks

Weekly injections of semaglutide typically helped obese people drop more than 12% of their body weight over 68 weeks, according to a new study that combined the diabetes drug with lifestyle intervention.

The treatment, given at a higher dose than diabetics receive, "is the most effective drug intervention we have seen for weight management," senior author Dr. Robert Kushner told Reuters Health in an email.

"Approximately 70% of participants in the study reached a weight loss of at least 10% of their baseline weight, a threshold that is meaningful for the improvement of multiple obesity-related health concerns, such as diabetes, high blood pressure, gastroesophageal reflux disease (GERD), and pain from arthritis of the knees," he said.

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The findings, published online by The New England Journal of Medicine, come at a time when developed countries are seeing an epidemic of obesity. Weight loss therapies have a long and checkered history.

Novo Nordisk, which sells injectable semaglutide under the brand name Ozempic and a daily oral version under the brand name Rybelsus, paid for the study. The company has asked the U.S. Food and Drug Administration to approve the drug as a weight loss regimen.

An editorial released by the Journal calls the new findings "a good beginning" but agrees with the Kushner team that the nausea, vomiting and diarrhea that can accompany the injections are a reason for concern, along with the higher risk of gallstones.

"In the real world, it seems unlikely that once-weekly subcutaneous administration would be a palatable or cost-effective solution in the long run," said the editorial by Deputy Editor Dr. Julie Ingelfinger and Dr. Clifford Rosen of Tufts University School of Medicine in Boston.

Whether the oral version of the drug would work as well is not known.

But Dr. Kushner, a professor of medicine and medical education at the Northwestern University Feinberg School of Medicine in Chicago, noted that "Subcutaneous injections have already been proven to be acceptable to patients with a variety of health problems, such as diabetes, psoriasis and rheumatologic diseases."

In the study, known as STEP 1, 1,961 volunteers with a body-mass index of at least 30 and at least one weight-related coexisting condition received either 2.4 milligram of subcutaneous semaglutide once a week or placebo. The lifestyle intervention received by all participants consisted of counseling, 2-1/2 hours of exercise per week and cutting 500 calories a day from the person's diet.

By the 68-week mark, mean body weight in the placebo group had declined by 2.4% and dropped by 14.9% with semaglutide injections (P<0.001). That translated to a typical loss of 30 pounds attributed to the drug.

Just over half the semaglutide recipients (50.5%) lost 15% of their body weight compared with 4.9% of placebo recipients.

They also showed better physical function and an overall improvement in their cardiometabolic risk factors.

However, rates for various side effects in the drug group were 27 percentage points higher for nausea, 16 points greater for diarrhea, 18 points more for vomiting and 14 points higher for constipation.

Further tests are needed to assess the long-term effects of the treatment. In addition, men and people of color were underrepresented in the trial.

A head-to-head comparison against other weight loss medications and bariatric surgery would be useful to doctors as well, the editorial said.

Dr. Kushner recalled that he " was surprised and gratified to see the unprecedented results from the medication. The fact that 50% of participants were able to lose at least 15% of initial body weight, and one-third lost at least 20% body weight is a game changer. Semaglutide 2.4 mg is by far the most effective drug intervention we have seen for weight management."

The treatment, if approved, "will not solve the public health crisis of obesity, but does offer help for those individuals who are struggling with their weight and present to their health care provider seeking treatment," he said.

—Gene Emery

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