Semaglutide Could Offer Long-Term Weight Loss and Cardiovascular Protection Effects

In the longest clinical trial yet of semaglutide, a prescription drug sold under the brand names Wegovy and Ozempic, researchers analyzed the drug's long-term weight loss effects. Published in Nature Medicine, the study was accompanied by an unpublished abstract and poster looking at Semaglutide’s potential cardiovascular benefits.

Semaglutide as an antidiabetic medication

Semaglutide is traditionally used in the treatment of Type 2 diabetes to help control blood sugar levels, along with diet and exercise. The antidiabetic medication binds to the glucagon-like peptide-1 (GLP-1) receptor to increase insulin secretion and suppress glucagon secretion. Recently, the drug has been popularized for its use in aiding weight loss. In 2021, it was the 90^th most prescribed medication in the United States, with over 8 million prescriptions.

Currently, the NICE guidelines only mandate treatment for up to a maximum of two years. As semaglutide’s popularity grows in both diabetic and non-diabetic communities, its long-term safety has been brought into question. Researchers from University College London set out to investigate the safety of semaglutide over an extended period of four years, along with its benefits in individuals of varying Body Mass Indexes (BMIs).

Does BMI impact the benefits of semaglutide?

Data from the clinical trial SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) were analyzed. The dataset included over 17,600 adults without diabetes, who were considered overweight or obese – body mass index >27 – and with pre-existing cardiovascular disease.

Initial results from the SELECT trial were published in November 2023, examining whether semaglutide reduced the risk of an adverse cardiovascular event. The latest study investigated the same results to see whether BMI impacted these effects.

Patients treated with semaglutide sustained weight loss for up to four years, with a mean reduction in weight of over 10%, compared to a 1.5% reduction in patients given a placebo. Participants typically lost weight continuously for 65 weeks before reaching a plateau. Weight loss also occurred in participants of both sexes and all body sizes.

Semaglutide’s benefits extend beyond weight loss

The researchers also presented their unpublished results, along with a poster at the 31st European Congress on Obesity, investigating whether Semaglutide’s cardiovascular benefits were driven by weight loss alone. The analysis found that a similar reduction in major cardiovascular adverse events was seen in participants who lost 5% or more of their body weight, as well as those who lost less than that, or those who gained weight.* 

Prof. Tricia Tan, a consultant in diabetes, endocrinology and metabolic medicine and chair in metabolic medicine & endocrinology at Imperial College London, commented on the study: “These new results, although not yet published, have important implications for our current practice in the UK.” 

“Even people who do not lose >=5% of weight seem to benefit.  This is important, as it tells us that there may be beneficial effects of semaglutide (and other similar medications) on heart disease which do not depend on weight loss,” said Tan.

Reevaluating prescription drug guidelines

The published study, combined with the abstract and poster, outlines the potential long-term benefits of semaglutide. Further studies are needed to understand the molecular basis behind these effects.

“It is very encouraging that continued treatment for 4 years or so is effective in helping people to lose weight at a clinically significant level of 10% on average.  Previously, the only evidenced and effective long-term treatment for obesity was weight loss surgery where we have evidence that surgery is capable of giving long-term weight loss for 20 years or so,” said Tan.

The results of the study also highlight the importance of continuously reevaluating guidelines for prescription medications as new research is developing.

Dr. Simon Cork, a senior lecturer in physiology at Anglia Ruskin University, and an expert on the physiology of body weight regulation also commented on the results: “Importantly one of the decisions by the UK health service to limit to 2 years was because of questionable long term cost effectiveness. That this data demonstrates improved cardiovascular and metabolic parameters continuing to 4 years may go some way to negating that argument.”

“This study also neatly demonstrates that obesity is a lifelong condition and the decision by NICE to limit prescription to 2 years (whilst they acknowledge its limitations) does a disservice to patients suffering with obesity,” said Cork.

Reference: Ryan DH, Lingvay I, Deanfield J, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024. doi: 10.1038/s41591-024-02996-7

*These research findings are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.