Semaglutide for secondary prevention after MI: Out with old, in with the new?

Darren is 63 and had an acute coronary syndrome and a stent fitted just over a year ago and he’s doing pretty well. His ACS came somewhat out of the blue as far he was concerned, although his diet and smoking history might have suggested otherwise. Anyway, it gave him a shock and Darren has done a great job of making significant changes - he’s walking more, his diet has improved and he’s managed to get off the cigarettes (albeit onto vapes). But he’s still struggling with his weight, as he always has done, with his BMI remaining about 32. ‘I’ve read that I can have one of those fat jabs if I’ve had a heart attack - I’d like to give it a go.’

All change in the world of CVD secondary prevention 

The winds of change are blowing through the secondary prevention management of cardiovascular disease after MI/ACS. For years it was simply aspirin, statin, beta-blocker, ACEI/ARB. A glut of recent evidence has questioned whether aspirin is the most effective long term anti-platelet, although debate rages as to which is, and beta-blockers in the absence of reduced LV ejection fraction do not seem to have any benefit in the long term.

GLP1 agonists for CVD secondary prevention?

So whilst we’re all getting used to using GLP1 agonists in primary care for type 2 diabetes, and (for small numbers currently) for those living with obesity, it may have come slightly from left field NICE’s recent recommendation (TA1153, May 2026) to roll out semaglutide for the secondary prevention of CVD in people even without diabetes, if they have overweight or obesity. NICE now recommend semaglutide for anyone with a BMI of >27 and established cardiovascular disease (previous MI, ischaemic or haemorrhagic stroke, or symptomatic peripheral arterial disease). That’s a lot of people. 

Where’s the evidence? 

The key trial supporting this recommendation is the SELECT trial. This RCT randomised over 17,000 people aged ≥45 years old with established CVD and a BMI of ≥27, without diabetes, to subcut semaglutide 2.4mg weekly or placebo. The primary CVD endpoint was a composite of death from CVD cause, non-fatal MI, or non-fatal stroke. Over 3 years there was a 20% reduction in the primary endpoint in the semaglutide group, all of which sounds pretty impressive. 

However, as is often the case, an excellent Drugs & Therapeutics review cuts the lofty trial results down to a more balanced level. As always relative risk reductions are often cited, especially in the lay press which reported this trial widely, rather than absolute risk reductions, which in this case was 1.5%, giving a number needed to treat (NNT) of 66. On top of that discontinuation rates were high with semaglutide (16.6% vs 8.2% with placebo) meaning ~1:12 people would likely stop the drug. There was also a suggestion that baseline risk factors were not ideally optimised but to be fair this probably reflects the real world situation with the general population. 

So, should we be prescribing semaglutide in Primary Care for this indication?

The SELECT trial is important - a well designed RCT which does show CVD benefits of semaglutide for people with established CVD and a BMI of >27, but the benefits would probably go in the ‘moderate’ category, and with the likely drop-out rates the absolute benefits across this population may be modest. Alongside this it’s important that more well established secondary prevention measures are not overlooked, including smoking cessation and exercise. To put in context, the NNTs (albeit over variable time frames) for preventing a further MI are 17 for 80mg atorvastatin, 21 for cardiac rehab, and 11 for smoking cessation (i.e. all significantly more effective than semaglutide). And whether we can prescribe in Primary Care will be largely dependent on our commissioners and local formularies, with NICE sitting on the fence here by noting ‘This guidance does not specify which setting semaglutide should be used in’. 

So back to Darren. Yes he is spot on in that he would fit the NICE guidance for consideration of semaglutide in addition to his standard secondary prevention, but there’s been no green light from your medicines management team that you can prescribe it. He’s disappointed, but you use the opportunity to review his secondary prevention more generally. He’s taking his atorvastatin 80mg regularly, and he’s off the cigarettes, and given his LV function was normal post stent, he can stop his bisoprolol as he doesn’t have any other indication for a beta-blocker. But he’d declined the initial offer of cardiac rehab, so you discuss that this is more likely to reduce his risk of a further heart attack than semaglutide and offer to a referral to your local cardiac rehab programme, which he’s willing to give a go.