Semaglutide for prevention or cure of HFpEF?

The results of the STEP-HFpEF trial point towards routine use of GLP-1 agonists in heart failure but this has to be balanced against conflicting guidelines and cost pressures in the NHS. There is also the question of whether these drugs should be used for prevention or treatment of cardiometabolic disease, says Vicky Ruszala, Specialist Cardiology Pharmacist, North Bristol NHS Trust.

The STEP-HFpEF trial excluded people with type 2 diabetes but there are ongoing trials with glucagon-like peptide 1 (GLP-1) agonists in patients with obesity, type 2 diabetes and heart failure with preserved ejection fraction (HFpEF).  Nevertheless, the results of the trial add to the understanding of cardio-renal-metabolic disease. “We know there’s benefit [from] GLP-1s in kidney disease, we know there’s benefit [from] GLP-1s in type 2 diabetes; we now know there’s benefit in heart failure as well”, says Ms Ruszala.

As a result, “cardiologists are now looking to say, well actually, anybody who’s got a BMI over 30 – because that was one of the cutoffs in the trial – should be given a GLP-1 agonist.   …..In the new ESC guidance (European Society of Cardiology guidance) for heart failure or heart disease and diabetes that was launched in August [2023], it already says anyone who has heart failure and type 2 diabetes should be given dual therapy with an SGLT-2 (sodium-glucose co-transporter-2 inhibitor) and a GLP-1”, she says. However, this is not yet in the UK heart failure guideline. “So, we have a lot of cardiologists that are looking to Europe and trying to do what Europe is doing whilst living in an NHS environment”, she says.

In theory, the trial paves the way for treatment of a group of patients who would derive significant benefit from receiving a GLP-1 agonist. Ms Ruszala’s previous experience as specialist pharmacist in diabetes taught her that it was “a huge struggle” to persuade prescribers to use a GLP-1 agonist for type 2 diabetes because of costs and organisational issues.

Should GLP-1s be routine treatment in heart failure?  

There are still many questions to be answered about the role of GLP-1 agonists. Ms Ruszala explains: “The difficulty we have in the NHS is the cost and …. the supply chain issue at the moment, you know. Let’s not stand aside from the fact that semaglutide is actually not available in the UK currently – it’s not likely to be available in the UK until 2024. So, we are sitting in a place where the science says it will be great and everybody kind of wants to do it and we know that we probably should do it. We have guidelines that say we shouldn’t, because we have nothing for HFpEF. We have [semaglutide for] type 2 diabetes but only if you’ve tried four or five other things [first].”

Currently the UK approach to the use of semaglutide in heart failure is different from the approach elsewhere in Europe. “I think it goes back to the prevention versus cure [question]. At the moment our guidance is set up as cure – when this has happened treat like this. [But] this kind of medicine is preventative. If you give semaglutide or another GLP-1 to somebody early in their diabetes pathway, early in their HFpEF pathway, the likelihood is that they will be much better, fitter and [generally well] for much longer throughout their journey.  So, we’re talking about more preventative, social kind of engineering to allow people to lose weight and thereby exercise more, … have less symptoms and …. be more productive”, she explains.

Talking to patients

Many patients will have seen headlines about the use of semaglutide in patients with heart failure and may be wondering if it is a suitable treatment for them. Ms Ruszala suggests there are some key points that could be included in conversations about this:

• This is the first trial of its kind and others will follow e.g. the SUMMIT trial which is to assess the efficacy and safety of tirzepatide in participants with HFpEF and obesity
• At present semaglutide is unavailable in the UK
• There should be a focus on optimising treatment with the available medicines. “Make sure people are on SGLT2 Inhibitors because they aid weight loss – they also treat diabetes like the GLP-1s”, says Ms Ruszala. “What pharmacists should be doing is encouraging patients to take control of themselves from a …. lifestyle perspective and supporting that change. Also ….. thinking about – ‘what can I use that I’ve currently got?’ – making sure people are on maximum dose ACE-inhibitors, making sure people are on beta-blockers if they’ve got a fast heart rate, getting an SGLT2 inhibitor in. All of those drugs that we currently have access to will still be of huge benefit”, she emphasises.

“Let’s use this as a good time to start doing all the other things and getting everything else better”, she says.

About Vicky Ruszala

As a specialist cardiology pharmacist, a large part of Vicky Ruszala’s work involves optimising medications for heart failure. She works on the specialist cardiology ward and also has two heart failure clinics each week.  She is an independent prescriber and has her own patient caseload.

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