SMART PEOPLE:
Dr Jan Westerink

A new, pooled analysis of data from Novo Nordisk’s Phase III trials SUSTAIN 6 and PIONEER 6 shows that semaglutide may help patients with type 2 diabetes live longer without a cardiovascular event. PharmaTimes talks to lead study investigator Dr Jan Westerink about the importance of these findings

Can you outline the analysis and its key findings?
We conducted a post-hoc analysis using the data from SUSTAIN 6 and PIONEER 6, which compared the glucagon-like peptide-1 (GLP-1) drug, semaglutide, with standard of care for people with type 2 diabetes who were at risk for cardiovascular disease. These trials had shown that there was a beneficial effect on reducing the risk of cardiovascular disease for people with type 2 diabetes by taking semaglutide. For this analysis we used the baseline data as well as the known benefit from these two trials (the Hazard Ratios) in combination with a life-time prediction model for cardiovascular disease.

The post-hoc analysis was performed using the Diabetes Lifetime-perspective prediction (DIAL) of cardiovascular risk model. Using this sort of model, we can estimate the time a patient has left without cardiovascular disease while at the same time taking into account the chances of dying from other causes. By adding known benefits from preventive lifestyle and/or medication we can estimate the absolute benefit from that intervention. So, instead of telling a patient that the risk will be 24% lower, we can discuss life-years gained from an intervention.

This means I can tell a patient, for example, ‘You currently have 23 years to go without cardiovascular disease and if you start taking semaglutide as part of your standard care treatment plan you could increase this by a maximum of 3 years’. Whether a patient is OK with this return on investment of up to three extra life-years free of cardiovascular disease, besides the effect on glucose and bodyweight, is part of the shared decision-making.

Why are these results so important, what do they mean for patients?
Using the lifetime model means we can provide more precise lifetime risk predictions for patients who have type 2 diabetes and cardiovascular risk. We can show that using a preventative treatment from an early age will give the largest benefit in the long run. Intuitive, of course, but now also quantifiable. On average, those who started with semaglutide increased their life expectancy by an average of 1.7 years, but this effect was smaller in older patients and larger in younger patients.
  
Besides the importance of age of initiation of the medication or life-style change, the most important determinant of the absolute benefit is the risk at baseline. Said otherwise, a patient with cardiovascular disease at baseline has in general an estimated larger benefit from adding a diabetes treatment with cardiovascular benefits to standard of care than someone without cardiovascular disease.

Do you expect the analysis to have a significant impact on prescribing practice for patients with diabetes and cardiovascular disease?
It is difficult to explain risk to patients and for many patients, the main focus needs to be enabling them to understand their risk and what they can do to reduce it, whether it be lifestyle interventions, improving their lower blood pressure or glucose and cholesterol levels as well as specific drugs like semaglutide. By using the results, we can provide patients with more precise quantitative information, allowing shared decision-making on when and whether to initiate an intervention and to improve compliance in the long run.

Current treatment guidelines tend to treat every patient the same while not all patients respond to the same treatments in the same way, and important for our analysis, with the same return on investment during a lifetime. By using lifetime risk models such as DIAL, we can find out a patient’s individual risk and personalise their treatment plan based in part on the patient’s preferences.