Semaglutide — a glucagon-like peptide-1 (GLP-1) receptor agonist found in medications such as Ozempic, Rybelsus, and Wegovy — has dramatic benefits for people with obesity and other weight management issues, a pair of new studies finds.
One study published in the journal Nature Medicine involved 17,000 adults without diabetes who were classified as overweight or obese.
In the study, researchers found that taking semaglutide-based medication resulted in an average weight loss of 10% of body weight and a reduction in waistline measurements of more than 7 centimeters (2.7 inches) over a four-year period.
“Weight-loss strategies have been transformed by the introduction of GLP-1s… compared to previous approaches to weight loss,” Luke Twelves, the medical director at clinical research firm Lindus Health who was not involved in the study, told Medical News Today. “This study adds further data to our understanding of the potential roles for GLP-1s and strengthens the case for their inclusion earlier in treatment pathways.”
The study, led by Dr. Donna Ryan of the Pennington Biomedical Research Center in New Orleans, also found that more than half of participants moved down at least one body mass index (BMI) category after two years of taking semaglutide (compared to 16% among a placebo group), and 12% reached a healthy BMI (compared to 1% of the placebo group).
“Such sustained weight loss of this magnitude is infrequently observed in clinical trials of other weight-loss interventions,” Michelle Routhenstein, RD, CDN, a preventive cardiology dietitian at EntirelyNourished.com who was not involved in the study, told Medical News Today.
She added that “waist circumference was measured because it specifically targets abdominal weight, which is closely associated with inflammation and the risk of heart disease.”
Antoni Adamrovich, the chief of medicine and co-founder of weight-loss program Tb2.health who was not involved in the research, told Medical News Today that the study indicated that GLP-1 drugs are significantly more effective than other popular weight-loss medications. Other weight loss medications such as phentermine or naltrexone/bupropion are associated with an average weight loss of 3% to 7% percent of body weight.
A companion study from researchers at University College London reported that GLP-1 drugs, which are used to treat type 2 diabetes as well as weight loss, also seemed to benefit the cardiovascular system regardless of how much weight people lost or what their starting weight was.
While this study, which has not been published yet in a peer-reviewed journal, did not involve people with diabetes, “it is likely that semaglutide would produce similar outcomes among individuals with diabetes,” said Routhenstein. “This is because semaglutide primarily functions by mimicking the actions of the body’s natural incretin hormone, GLP-1, to slow down the absorption of food, allowing for more satiety and controlled blood sugar metabolism.”
Positive outcomes were seen among all genders, races, ages, regions, and body sizes when compared to placebo effects, researchers said.
“Our long-term analysis of semaglutide establishes that clinically relevant weight loss can be sustained for up to four years in a geographically and racially diverse population of adults with overweight and obesity but not diabetes,” said Ryan in a press statement. “This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses. While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis, and anxiety and depression would benefit from effective weight management.”
John Deanfield, a professor of cardiology at University College London who led the companion study, added that the findings suggest that semaglutide “has other actions which lower cardiovascular risk beyond reducing unhealthy body fat.”
“These alternative mechanisms may include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, or a combination of one or more of these,” he said.
Side effects of semaglutide treatment can include gastrointestinal symptoms such as nausea and diarrhea as well as a higher risk of developing gallbladder stones. However, the researchers said that negative symptoms were actually lower among the semaglutide recipients than in the placebo group.
The findings were presented at the May 2024 European Congress on Obesity.
The data were sourced from the ongoing Semaglutide and Cardiovascular Outcomes (SELECT) research trial, launched in 2018. In 2023, studies based on SELECT trial data on a similar population found that taking semaglutide for more than three years reduced risk of heart attack, stroke, and death from cardiovascular disease by 20%.
Adamrovich said more research to show the impact of GLP-1 treatment beyond four years would be beneficial “to see if the weight loss and cardiovascular benefits were sustained long term.”
“It would also be helpful to conduct some follow-up studies focusing on certain heart-healthy diets and moderate-intensity exercise in conjunction with semaglutide or tirzepatide use,” he said.
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