SELECT showed semaglutide reducing cardiovascular events in people who already had cardiovascular disease, and its inflammation substudy is covered in inflammation fell before the weight. The question this addresses is what that would mean for the far larger group who are at risk but not yet diagnosed [1].
The method is worth describing precisely, because it determines what the numbers are. A risk equation predicting ten-year cardiovascular events was fitted using five factors — BMI, HbA1c, systolic blood pressure, high-sensitivity CRP and non-HDL cholesterol. It was then applied to survey participants twice: once with their real values, and once with those five values shifted by the placebo-adjusted amounts SELECT recorded. Among 21,720 people with a BMI of 27 or above and elevated baseline risk, projected incidence fell from 13.82% to 10.83%.
The load-bearing assumption is that the drug’s benefit runs entirely through those five risk factors. There is direct evidence from SELECT itself that it does not: inflammation fell before major weight loss and in participants who lost none, which means at least part of the mechanism is not captured by moving BMI and cholesterol on a spreadsheet. That cuts in the model’s favor — if some benefit arrives by another route, this underestimates it. The opposite risk, that a risk equation fitted in one population behaves differently in another, cuts the other way.
The absolute figure is the one to carry. Three fewer cardiovascular events per hundred people over a decade, in a group at elevated but not established risk, is a meaningful public health quantity and a modest personal one. Absolute reductions were larger in men (3.14 points) than women (2.70), with near-identical relative reductions — the same relative-versus-absolute distinction set out in the semaglutide and tirzepatide comparison and the FLOW numbers needed to treat.
What the analysis usefully establishes is scale. If these effects hold in primary prevention, the number of people who would need treating to realize them is enormous, and the cost question that follows is not a clinical one. The secondary analyses accounting for reduced compliance are the most honest part of the paper, given that most people stop within a year — a figure this site tracks alongside the network meta-analysis of nineteen drugs.