Wegovy approved to cut cardiovascular risk

The popular weight-loss drug has been approved to treat cardiovascular disease in patients who are overweight or obese.

The Therapeutic Goods Administration (TGA) approval is based on results from the SELECT double-blind, randomised, placebo-controlled trial – a global study conducted in 41 countries, including Australia, with over 17,000 participants.

Australian Pharmacist spoke with Professor Stephen Nicholls, lead of the Australian arm of the SELECT trial, about the significance of this new indication and what pharmacists need to know.

What impact does a Wegovy have on cardiovascular risk?

It has been well known for many years that being overweight or obese is a major risk factor for heart disease, said Prof Nicholls.

‘And in people who have had a heart attack, the presence of overweight or obesity is associated with a worse risk of having another event – but there’s nothing specifically that we’ve been able to do for these people.’

For decades, clinical trials for weight loss drugs have shown no benefit in reducing cardiovascular risk in these patients.

‘But here you have a trial where we specifically targeted people who were overweight, and it reduced their risk,’ he said.

Participants in the SELECT trial had cardiovascular disease, overweight or obesity, but without diabetes, said Professor Stephen Nicholls.

‘The trial found that giving them semaglutide reduced their risk of having another event by 20%,’ he said. ‘That’s a game changer – both for the drug and the field.’

What makes a patient eligible for Wegovy for cardiovascular disease?

The new TGA indication for Wegovy is as a complementary therapy for reducing major adverse cardiovascular events such as cardiovascular death, heart attack, or non-fatal stroke in adults with:

• established cardiovascular disease
• A Body Mass Index  ≥27 kg/m2
• without established Type 1 or Type 2 diabetes.

The recommended dose of Wegovy for these patients is 2.4 mg weekly, said Prof Nicholls.

What other cardiovascular risk factors does Wegovy help to mitigate?

While weight loss is a significant advantage, the SELECT trial revealed that semaglutide has other benefits for patients with cardiovascular disease.

‘It wasn’t designed to be a weight loss trial, and the findings are not [centred around] weight loss,’ said Prof Nicholls.

Along with losing around 9% body weight, 30–40% reductions in inflammation markers were recorded – along with a reduction in triglyceride levels. 

‘Reduced triglyceride levels are really going to translate to less small, dense (low-density lipoprotein) cholesterol,’ he said.

‘We saw a small increase in high-density lipoprotein cholesterol, which we think is protective, and blood pressure reductions which are not insignificant.’

Other benefits include improved glucose control.

‘We saw far less people developing diabetes in the trial who were treated with the drug compared to placebo,’ said Prof Nicholls.

Has a submission been made to PBAC?

Novo Nordisk submitted two applications to the  Pharmaceutical Benefits Advisory Committee (PBAC) to have Wegovy added to the Pharmaceutical Benefits Scheme (PBS) for severe obesity. These applications were rejected.

‘Our two previous submissions to the PBAC did not include patients with heart disease as the indication for established cardiovascular disease was not approved,’ a spokesperson for Novo Nordisk told AP. ‘Novo Nordisk plans to resubmit Wegovy to the PBAC in 2025.’

While these are new medicines that come at a cost, a choice has to be made around where they will have the most benefit, said Prof Nicholls.

‘We’ve seen that play out in the way drugs have been approved in the cardiovascular space,’ he said. ‘But we also have to think that this isn’t just about reducing the risk that you’re going to have another heart attack. There are a whole host of health benefits, including social and economic benefits, that come along with using this drug.’

In the right patients, there’s potential for the cost-benefit analysis to be ‘quite favourable’.

‘Hopefully, the government agrees,’ said Prof Nicholls.

What are the benefits for high-risk CVD patients with multimorbidities?

As a practicing cardiologist, Prof Nicholls said patients rarely have isolated heart disease.

‘They might also have liver disease, joint replacements, be overweight or obese or have sleep apnea,’ he said.

Glucagon-like peptide-1 receptor agonists have favorable effects on a range of multimorbidities associated with cardiovascular disease, such as improved kidney function, liver function and sleep apnea – along with orthopedic benefits through weight loss, said Prof Nicholls.

‘These drugs are going to be really helpful,’ he said. ‘So the TGA approval is a big deal.’

How long should cardiovascular patients stay on Wegovy?

For the long-run, said Prof Nicholls.

‘The median treatment duration in the trial was just under 3 years (34 months),’ he said. ‘The intent is that you’re on these drugs long term.’ 

Once a patient is diagnosed with heart disease, they are in a different risk category.

‘With those people, we don’t take our foot off the pedal,’ said Prof Nicholls. ‘Because we know they are at a substantially higher risk of having an event in the future, and there are things we can do to significantly mitigate that risk.’

Should other cardiovascular medicines be titrated if Wegovy is initiated?

In a nutshell, no.

‘If I’ve got a patient in front of me with heart disease, and I think they’re at a really high risk of having another [cardiovascular] event, I tend to treat all their risk factors more intensively,’ said Prof Nicholls.

‘If these drugs are causing blood pressure and cholesterol levels to go down a bit, I’m not backing off on other therapies.’ 

This is a lesson learned when PCSK9 inhibitors were introduced.

‘They lower LDL really effectively, so people continue to ask, “should we back off on the statin?”’said Prof Nicholls. ‘And then the answer is no.’

What do patients need to know about adverse effects?

When initiating therapy, pharmacists should discuss the likelihood of gastrointestinal (GI) adverse effects, said Prof Nicholls.

‘We do see a lot of GI side effects, and a lot of it settles down,’ he said.

In some patients, these adverse effects might persist,

‘As with a lot of chronic therapies for reducing cardiovascular risk, the reality is that we see people come off these therapies,’ said Prof Nicholls.

‘So it’s about talking to a patient at the start about [the potential adverse effects] so there can be a shared decision-making process about commencing therapy.’

It’s important to work with the patient to see what could help them remain on the therapy in the long term. 

‘Because long-term therapy is what’s actually going to produce long-term benefits,’ he added.

What complimentary lifestyle advice should pharmacists provide?

As good as medications such as statins, and now Wegovy, are at reducing cardiovascular risk – good lifestyle advice is key.

‘As healthcare professionals, we sometimes over-complicate lifestyle advice, so patients can feel that lifestyle changes are hard,’ said Prof Nicholls. ‘My view is that we need to try and keep that as simple as possible.’

Medications aren’t a replacement for good lifestyle, but an adjunct.

‘When people are trying to [improve] their diet, physical exercise and activity and not smoke, that’s where you have the best chance for these therapies to work.’