The Big Interview – Dr Jan Westerink
Novo Nordisk is leading the way in predicting health outcomes with their pioneering semaglutide studies SUSTAIN 6 and PIONEER 6.
A post-hoc analysis of the data from these two trials has shown the possibility of predicting when a person might start to develop cardiovascular disease and their cardiovascular lifetime risk.
Lead study investigator, Dr Jan Westerink, talks to The Diabetes Times about the process and how the findings might radicalise the future.
What were the main findings of the post-hoc analysis of SUSTAIN 6 and PIONEER 6?
The main finding is that not all patients benefit the same from any treatment. What we did was we used the data from SUSTAIN 6 and PIONEER 6, which compared semaglutide with standard of care for type 2 diabetes.
These trials had previously shown there was beneficial effect on reducing the risk of cardiovascular disease by taking semaglutide. The post-hoc analysis of this data showed that including semaglutide in addition to standard of care may extend a patient’s life without a cardiovascular event, such as heart attack or stroke, in people with type 2 diabetes and high cardiovascular risk for up to three years.
We found there was a hazard ratio here of 0.76 which means there’s a 24 per cent reduction in the risk of developing cardiovascular disease.
Using this data, we developed a lifetime model that calculates the person’s cardiovascular disease (CVD) pre-life expectancy. This means I can calculate, on average, what someone’s age will be when they first develop CVD and using this with the findings from the two studies, I can calculate the absolute benefit of taking the medication.
This means I can tell a patient, for example, ‘you’ve still got 35 years to go without cardiovascular disease, but you do still have type 2 diabetes’. I can suggest if they start taking semaglutide as part of their standard care treatment plan, then I could tell them they could probably reach a maximum of 38 years. That means they will have effectively gained three more years of their life. This is a completely new way of discussing concepts and risk with patients.
So, your findings allow for more precise and bespoke predictions?
Exactly! It’s a bit like starting a savings account. If you’re young, then you get a larger return on your investments. Applying the same logic to starting preventative medication can also mean greater life benefits too. Of course, there’s also lifestyle change to consider too.
We can show that using any preventative treatment from an early age will give most patients a larger benefit. On average, those who started with semgalutide increased their life expectancy by an average of 1.7 years. But some people had less than one year and some patients had up to three years.
We found the outcome was dependent on several variables, including how old the participants were when they initiated the treatment and also what their risk was at baseline.
The example I like to use is if I have two patients who are twin brothers. One has type 2 diabetes and cardiovascular disease, and the other brother just has type 2 diabetes. They’re both young and both have a long-life expectancy. But as expected, life expectancy is shorter in the brother who has both CVD and type 2, but if he starts to use an effective treatment, whether it be lifestyle intervention or in this case semaglutide, he will win more years than his brother.
It’s these sorts of comparisons that will help us to help the patient understand. Now we have real evidence so we can say to the patient if they start taking this drug, or change their life, stop smoking, or start a lipid-lowering therapy they will enjoy real benefits. Some may be interested, some may not be, but it’s all about individualised treatment.
How could the results impact the lives of people with type 2 diabetes?
It’s arming us as the care givers and healthcare professionals with the knowledge to present patients with the findings. For many patients, it’s about understanding. By using the results, we can provide patients with precise information, allowing them to start preventative treatment at an earlier age. Using this risk model in future practice is a good way to determine their risk and look at treatment.
An interesting concept is that if someone has terminal cancer and I offer them a simple trick to give them just one day longer to their life, they will probably take it. If I was to tell a 20-year-old guy that he should stop smoking as it would give him 10 years of life expectancy, he probably won’t do it because he can’t see that far into the future.
All things surrounding time are completely irrational. Now it’s all about whether taking a drug for 16 years of your life in exchange for an extra two years life is a decent return on investment. When we asked patients and doctors in the Netherlands what they thought would be an acceptable return on investment, there was a large difference of opinion. Some patients were perfectly fine with taking a drug for the rest of their lives with only half a year of benefits, but some will only agree to taking a preventative drug if it would guarantee another five years onto the expectancy.
But of course, opinions change as people get older, when grandchildren come along and people start to develop CVD.
From your perspective, what immediate impact has COVID-19 had on people with diabetes?
I think during the lockdown phase patients have found it more difficult to get more exercise which will increase their bodyweight and cause poorer glycaemic control. In addition, it’s more difficult for patients to speak with their GP or whatever diabetes healthcare professional they are used to seeing. So, there’s a lot less connection with their healthcare professionals.
People with diabetes are more on their own, and we’re able to see how patients are managing with self-management of their disease.
What impact will COVID-19 have on the long-term management of diabetes post the pandemic?
Presumably, I think some patients might see that they are up to the challenge of self-management, that they can actually do it. But I think we’ll also discover there are some that actually need more guidance. But it’s difficult to say as it’s a bit like determining the long-term benefits of treatments. Some patients will do fine and some will get quite poorly. At the moment healthcare professionals are doing more phone or video calls with patients and I think this is probably something that’s here to stay. There will probably be some analysis in the future which will find it’s more cost effective.
What’s your biggest achievement in diabetes care?
I think it would be what we have contributed to developing individual risk predictions like we’ve just discussed, which will be hugely helpful in the future. We’ve also shown that whether it be lifestyle intervention, blood pressure lowering, lipid lowering therapy or using glucose lowering drugs, there’s not one simple treatment plan that will help all patients.
We know that benefits differ from person to person so that does mean the patient can take back control should they wish to. We should be helping our patients in making the right decisions for their help. What I’m most proud of is the contribution I’ve made to this website: https://u-prevent.com/, where all our lifetime models can be found and used to calculate risk.