Medicine Matters diabetes

VERIFY was actually a very important study for me because it was looking at patients who are newly diagnosed with type 2 diabetes, who we perhaps are used to initiating on monotherapy, but are actually very much at risk of therapeutic inertia. And we want to really ensure that these patients start their journey on the right foot.

And this combination therapy has really been spoken about for quite a while now. It's the first time we've really seen a study address it head on. And it's given us some really interesting data to analyze and move forward with.

I thought it was really interesting that they used a DPP-4 inhibitor in this trial. Metformin combined with DPP-4 inhibitor, well actually, they complement each other quite well in terms of their mechanism of action. And in the patient who's just been diagnosed with diabetes at an early stage, I think it would work quite well.

It has opened the door, however, for further studies going forward, particularly with the impressive results we've seen with SGLT2 inhibitors and GLP-1 receptor agonists. So I think there's more work to be done, however, when we look at cost effectiveness, when we look at budget constraints in the various health services around the world, I can see that DPP-4 inhibitors with Metformin, particularly in the next few years, will be quite an economical choice that actually gives quite a beneficial glucose control with some impactful durability as well. So I can certainly see it being a popular choice, which will no doubt be implemented at the coalface, particularly in primary care.

The effect of the combination group was actually really good. What we saw was there was a delay in failure in the first outcome, the failure being the HbA1c rising above 7%. And actually, we saw patients with combined therapy taking up to about five years before there was failure, on average, compared to the monotherapy group, where there was failure at around three years. So it's quite a substantial difference, actually.

Going beyond that, when the monotherapy group did have step up to combined therapy, we saw that even then, those who were initially started on the combined therapy continued to show benefit in terms of glucose control, as far as durability was concerned. So that was also quite an interesting feature of the results, as well.

Is the evidence from VERIFY strong enough to justify guideline changes?

I think so. I think the evidence from VERIFY certainly has shown that there is a benefit in terms of glucose control. I think it's also just moving us in the right direction in terms of avoiding therapeutic inertia, which we know there are several factors at play there, and just by starting combination therapy we're not going to overcome that. But it certainly focuses our minds as clinicians on the fact that it is important to consider more than one step at a time, and actually try to combine different options that are available to us in our toolbox.

An interesting exploratory outcome that was looked at during the study was that of cardiovascular events, so macrovascular complications. And we did find that the group that was initiated on combined therapy did have fewer cardiovascular events. We can't take a great deal from this. Obviously, it was not a significant difference. This study was not powered to be a cardiovascular outcome trial, and we were looking at very low-risk patients that had just been diagnosed with type 2 diabetes. But it was interesting nonetheless. I am perhaps more interested in the microvascular outcome data that's yet to be presented. But I think we all know that with early glucose control, that ought to be something that will show some good results in terms of microvascular protection. And that's certainly something I think which will give us some benefit for those early, early years in patients with type 2 diabetes.