What Does the Positive Outcome of the SELECT Trial Mean For People Living With Obesity?

This week Novo Nordisk released the topline results of the SELECT trial, apparently showing that once-weekly treatment with 2.4 mg semaglutide s.c. results in a 20% reduction in the composite endpoint of CV death, nonfatal MI or nonfatal stroke (three-component MACE) compared to placebo.

This is no doubt a landmark achievement, given that enrolment into the SELECT Trial  was limited to individuals with overweight or obesity and established cardiovascular disease (CVD) but WITHOUT  diabetes (the reduction of CV outcomes with semaglutide in people with high CV risk and diabetes has already been demonstrated in the SUSTAIN-6 trial).

The main question that pops up is whether or not these findings are related to and largely explained by the weight-loss effects of semaglutide. Indeed, at this point we don’t even know how much weight the treatment group lost or sustained over the five year duration of the study.

But if we assume that people on semaglutide did experience and sustained more weight-loss than those on placebo, and that there may even be a demonstrable dose-effect relationship, such that those who lost the most weight experienced the greatest benefit, one should hope that this study will make a strong case for better access to obesity treatments – at least for people with overweight or obesity who also have established CVD. 

But, what will these results mean in terms of better access to obesity medications for people with overweight or obesity WITHOUT established CVD? 

Probably not much. In other words, for younger people with excess weight not (yet) presenting with established CVD, even if they are experiencing other health problems that may be improved by obesity treatments, SELECT may change little. 

Demonstrating that early treatment of obesity will reduce morbidity and perhaps mortality in those with EOSS Stage 2 or even Stage 1 obesity (rather than just EOSS Stage 3 as in SELECT), would require a much larger and probably longer study and is unlikely to happen anytime soon. 

Thus, while SELECT may well open the door to obesity treatments for people with obesity, who have established CVD, most people living with obesity will probably continue to struggle with access.

On a more positive note, however, SELECT should clearly reassure us that the long-term use of 2.4 mg semaglutide, even in high-CV-risk individuals, is rather safe and may even save lives.

This alone is a major landmark in terms of medical treatments for people living with obesity.

@DrSharma

Disclaimer: I have received honoraria as an independent medical, research and/or educational consultant from various companies including Aidhere, Allurion, Boehringer Ingelheim, Currax, Eli-Lilly, Johnson & Johnson, Medscape, MDBriefcase, Novo Nordisk, Oviva and Xenobiosciences.