Rybelsus ( Semaglutide ) for Weight loss
Rybelsus ( Semaglutide ) May Complement a Healthy Lifestyle to Increase Weight Loss
The trial included 1,961 adults with a body mass index (BMI) of 30 or greater — the threshold for diagnosing obesity — or with a BMI of 27 or higher and at least one weight-related medical problem. None of the participants had type 2 diabetes at the start of the trial, but several of them had prediabetes, or slightly elevated blood sugar levels.
All of the trial participants received nutrition counseling and were advised to get at least 150 minutes a week of physical activity. People who received Rybelsus in addition to this support to promote lifestyle changes lost an average of 33.7 pounds by the end of the 68-week trial, compared with an average of just 5.7 pounds in the group that received a placebo.
People taking semaglutide also experienced greater improvements in cardiovascular risk factors like BMI, waist circumference, blood pressure, and blood sugar than participants given a placebo.
The most common side effects of semaglutide were gastrointestinal issues, including nausea, vomiting, and constipation, which were experienced by nearly half of those on the drug. Most participants stuck with the trial, however, with only about 4.5 percent of people on semaglutide and 0.8 percent of people on placebo discontinuing treatment due to gastrointestinal problems.
Safety of Semaglutide and Other Weight Loss Drugs
Many drugs that have been approved for weight loss in the past have been withdrawn due to serious and potentially life-threating side effects, according to an editorial published in conjunction with the new study in the New England Journal of Medicine. These include several amphetamines that caused addiction; fenfluramine, which caused heart valve damage; and lorcaserin, which increased the risk of cancer.
Semaglutide is in a family of medicines known as GLP1 agonists, which mimic the action of a hormone that causes people to feel full. A similar drug, liraglutide, is already approved for weight loss in addition to type 2 diabetes.
“Semaglutide appears to be similarly safe compared to other medications in its class such as liraglutide,” says Beverly Tchang, MD, an assistant professor at Weill Cornell Medicine who wasn’t involved in the semaglutide trial.
“And at the 2.4-milligram dose, semaglutide has shown the greatest amount of weight loss among all other currently approved anti-obesity medications,” Dr. Tchang adds.
Semaglutide Beats Weight Loss Achieved With Other Drugs
Several other medications approved for weight loss have not achieved results as dramatic as those seen with semaglutide in the current trial, according to a review of anti-obesity treatments published in January 2021 in Current Obesity Reports. To try to isolate the effect of weight loss drugs alone, researchers subtracted the weight lost in the placebo group, which only followed lifestyle interventions, from the amount of weight lost in the study group, which followed lifestyle interventions and took medication.
They found that participants lost an average of 6.8 percent of their body weight with phentermine/topiramate, followed by 5.4 percent with liraglutide, 4.0 percent with naltrexone/bupropion, and 2.9 percent with orlistat.
By contrast, people on semaglutide in the current trial lost 12.4 percent of their body weight after researchers performed the same calculation.
Evidence So Far Suggests Semaglutide May Offer Lifelong Treatment for Obesity None of these weight loss medications are as effective as surgical weight loss, which can help people lose about 30 percent of their body weight, says Frank Greenway, MD, director of the outpatient research clinic at the Pennington Biomedical Research Center in Baton Rouge, Louisiana.
However, not all patients are good candidates for surgery and the results of the current trial suggest that semaglutide may be a safe and effective intervention for long-term weight management, says Dr. Greenway, who wasn’t involved in the clinical trial.
“The FDA has always put the bar for safety high for anti-obesity drugs and has had a quick trigger for withdrawing them when unexpected side effects are identified,” Greenway says. “Semaglutide is less likely to have that problem than other truly novel medications.”
That’s because drugs in the same family of medicine, GLP1 agonists, have already been on the market for years, limiting the potential for surprise safety issues to emerge if the drug wins approval as a weight loss treatment, Greenway says.
The safety and effectiveness seen with semaglutide in the current trial are reassuring, agrees Tchang, particularly because patients may remain on the drug for the rest of their lives.
“Obesity is a disease just like high blood pressure or high cholesterol, and you don't stop taking your blood pressure medication when your blood pressure is normal because when you stop, your blood pressure goes up again,” Tchang says. “Similarly, when patients stop an anti-obesity medication that helped them lose weight, their weight can go up again too.”
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