JAMA Cardiology Letter Highlights Limitations and Risks of Semaglutide

WASHINGTON, D.C.—Limited effectiveness, weight regain, and high prevalence of adverse events are the three key limitations of semaglutide highlighted in a letter published in the Journal of the American Medical Association (JAMA) Cardiology. The letter is published in response to research that found that more than half of U.S. adults, 137 million, are eligible for semaglutide for weight loss.

“This research found that half the U.S. adults are eligible for semaglutide for weight loss, and while the authors correctly cite access and cost as important barriers, there are other significant limitations and risks,” says letter author Vanita Rahman, MD, DipABLM, internal medicine and lifestyle medicine doctor with the Physicians Committee for Responsible Medicine, a public health advocacy nonprofit.

For those taking semaglutide, the weight loss plateaus, and the average body mass index (BMI) remains in the obese category. After four years of semaglutide treatment, only 12% of participants in the SELECT trial attained a normal BMI, and 44.6% and 43.3% of participants had BMIs in the overweight and obese categories, respectively.

Weight gain recurs after the medication is stopped. In the STEP-1 extension study, rapid weight regain was seen with semaglutide discontinuation.

Semaglutide is associated with a high prevalence of adverse events, and its long-term safety is unknown. In an observational study, semaglutide was associated with a more than fourfold and sevenfold risk of nonarteritic anterior ischemic optic neuropathy in people taking semaglutide for type 2 diabetes and weight loss, respectively.

Plant-based dietary interventions, on the other hand, have led to significant weight loss along with improvements in cardiometabolic risk factors. In the BROAD study, a low-fat plant-based diet led to an average weight loss of 12.1 kg at 6 months compared with an average weight loss of 1.6 kg in the standard-care group. The plant-based group also experienced larger reductions in total cholesterol.

Dr. Rahman adds, “Obesity and overweight are highly prevalent conditions associated with considerable morbidity and mortality, and successful weight loss interventions can lead to important reductions in cardiometabolic risk.”

Though semaglutide can lead to meaningful weight loss in some individuals, it comes with important risks and limitations. On the other hand, plant-based diets are a safe, low-cost treatment option with research-proven benefits.

Half of U.S. adults say they know eating a plant-based diet can improve their health and help prevent chronic diseases, according to a recent Physicians Committee/Morning Consult survey. Yet just 1 in 5 primary care practitioners discuss this lifesaving message with patients.

“This provides us as health care professionals with an opportunity to support and guide our patients toward nutrition interventions that work and reduce the risk of chronic diseases that affect millions,” Dr. Rahman says.