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Semaglutide found to sustain weight loss for four years and cut CVD risk

Weight loss in patients taking semaglutide can be sustained for up to four years, according to results from the SELECT study presented at the European Congress on Obesity and published in the journal Nature Medicine.

A second as-yet-unpublished analysis from the same trial, also presented at the conference, found semaglutide delivered cardiovascular benefits irrespective of starting weight or amount of weight lost.

It follows a report last year that adults with overweight or obesity but not diabetes taking semaglutide for more than three years had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease.

Now, the updated analysis by UK researchers of the participants, who had already had a heart attack, stroke or had peripheral artery disease, suggests that even those with relatively mild levels of obesity, or those who only lose modest amount of weight, may have improved cardiovascular outcome.

Both findings have potential implications for current UK practice, experts noted.

Sustained weight loss was seen for men and women and across all races, ages and body sizes, the researchers reported, for what is the longest trial of the drug for this purpose to date.

In all, weight loss continued to Week 65 and then plateaued for four years, with participants’ losing on average 10.2% of their body weight and 7.7cm from their waistline, compared with 1.5% and 1.3cm respectively in the placebo group, the study found.

Study author Professor Donna Ryan, from Pennington Biomedical Research Centre in Louisiana, US, said: ‘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.’

Professor John Deanfield, professor of cardiology at University College London and consultant cardiologist at the Barts Heart Centre, London, UK, carried out the analysis on cardiovascular risk. He said there were important clinical implications for those with existing cardiovascular disease but cautioned against extrapolating the data more widely because it was not a primary prevention trial.

‘Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the SELECT trial and are likely to derive benefit from taking semaglutide on top of their usual level of guideline directed care,’ he said. 

‘Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat.’

This could include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, he said.

Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, said it was important both that longer-term use of this approach for the treatment of obesity appears safe and that treatment is reported to significantly reduce the risk of death from heart diseases.  

‘The latter confirms what we have long suspected, notably, that the increase in the risk of a number of cardiovascular diseases associated with obesity will be reversed is weight is reduced,’ he said.

‘This is likely to relate to a number of mechanisms, including improved blood fat profiles, lower blood pressure, less diabetes and less inflammation related to all of the above.’

He said a lot had been made of the potential benefit ‘beyond weight loss’ but in his view it was ‘all likely to be due to the reversal of the abnormal and damaging biology of obesity by reversing the weight gain’.

Professor Tricia Tan, professor of metabolic medicine and endocrinology at Imperial College London, said it suggested that NICE guidelines needed to be updated to increase funding for treatment up to four years or more.

‘Secondly, we also need proper funding from the NHS to implement the specialist clinics necessary for us to effectively deliver these life-saving and cost-effective medications,’ she added.

A version of this article was originally published by our sister publication Pulse.