Dear Editor
Jacqui Wise (BMJ 2023;383:p2668) provides a prompt and helpful overview of the recently published study on the effect of semaglutide on cardiovascular outcomes in people aged ≥45 years with cardiovascular disease (but not diabetes) and a BMI ≥27 kg/m2. The study provides some welcome evidence on the effect of semaglutide on clinically important cardiovascular events and on adverse events leading to withdrawal from treatment. It is, however, worth looking beyond the media hype that has accompanied the trial results and considering some of the details.
Unfortunately, headlines announcing the publication of the trial results presented the relative risk reduction in the primary composite endpoint of 20% rather than the absolute risk reduction of 1.5% .(1) Based on the effect of semaglutide on the composite primary endpoint (6.5% vs 8.0%), 67 people would need to be treated for 34 months to prevent one primary endpoint event. For the individual components of the composite endpoint, the 95% confidence interval for the hazard ratio (HR) was less than 1 for only one of the three outcomes and the secondary endpoint of death from cardiovascular causes was not statistically significant:
Nonfatal myocardial infarction 2.7% vs 3.7% (HR 0.72, 95% CI 0.61 to 0.85)
Death from cardiovascular causes 2.5% vs 3.0% ( HR 0.85, 95% CI 0.71 to 1.01; p=0.07)
Nonfatal stroke 1.7% vs 1.9% (HR 0.93, 95% CI 0.74 to 1.15)
The risk of an adverse event leading to “permanent discontinuation of trial product” was much higher in the semaglutide group than the placebo group (16.6% vs 8.2%), an absolute risk increase of 8.4% or a relative risk increase of 50%. This data suggests that one person would discontinue treatment for every 12 people treated with semaglutide. The majority of these adverse effects related to gastrointestinal disorders (10.0% vs 2.0%).
Although we do have information on the indicative UK price for Wegovy, which ranges from £73.25 for the lower strength pre-filled pens to £175.80 for the highest strength pen, the price agreed by NICE with the company for its use in the NHS in England has not been made public.
In October, DTB published an article (https://dtb.bmj.com/content/early/2023/10/25/dtb.2023.000007) by Professor Joel Lexchin and Professor Barabara Mintzes that explores the the evidence for semaglutide, discuss the hype surrounding the drug and highlights the need to tackle the other determinants of obesity. (2) They emphasise the importance of addressing the complex factors that contribute to the development of obesity rather than relying on medication as a damage limitation exercise.
1. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023. doi:10.1056/NEJMoa2307563. [Epub ahead of print 11 November 2023].
2. Lexchin J, Mintzes B. Semaglutide: a new drug for the treatment of obesity. Drug Ther Bull. 2023. doi:10.1136/dtb.2023.000007 [Epub ahead of print 25 October 2023].
Semaglutide reduces the absolute risk of major cardiovascular events by 1.5%