PINAR TOPSEVER: My main take-home messages from the TriMaster said study would be, first of all, from a philosophical point of view, I thought that it's a great opportunity that such a trial, in the sense that this single case design was used, that was sort of randomized, blinded, and of one trial design, the TriMaster study, could be implemented for a condition as prevalent in the general population as type 2 diabetes.
And we family physicians, GPs, do look after this aging population, this multimorbid aging population and type 2 diabetes risk being very prevalent there. And it's great if you have this crossover design where each patient has the opportunity to try different medications for the same indication.
And then we can see with the biological markers how-- we can look at the efficacy. And we can also look at real-time effectiveness. And what's the most challenging part, which we always figure out during the course of therapy together with our patient on this journey is the patient preference, which actually sort of defines adherence and, most of all, persistence, because type 2 diabetes is a condition which cannot be cured and which requires lifelong therapy.
And in that case, persistence is as important as adherence. So I found this study design fantastic because it goes very much along with the philosophy of a holistic approach and person-centered care, which is one of the core competencies of the clinical discipline of family medicine general practice as you know.
So that would be one, let's say, philosophical and methodological take-home message that I would wish for many of those trials to be conducted in this design. And the other take-home message is that with such trial results, we could really see which patients will be most fit for which drugs. So we could estimate who would be the non-responders and the non-adheres, non-persisters. And we could see who would be the ones who at least from a clinical and biological point of view. And in this trial, the primary outcome was change in hemoglobin A1C. So that was a very glucocentric trial.
We could then foresee how that would work. And so we could overcome this uncertainty about comparative effectiveness of drugs because if we look at the guidelines, they are even tiring to look at. So many boxes and risk stratification. And there's a risk stratified approach.
Then there's the glucocentric approach. Then there's this approach, which is about avoiding side effects, the safety approach, and so on. And so we would have a path about comparative effectiveness and would somehow overcome this individual heterogeneity of effect of drugs. So that's my main take-home message that I find this precision medicine approach, very in line with person-centered care, which is one of the core competencies in primary care.
Yeah, I do think there should be other factors to stratify by. And again, talking about type 2 diabetes because this is such a good example for a multimorbid disease entity where it all starts with overweight, obesity, insulin resistance, and then the carrier, the dysglycemic carrier goes on. And there are modifiable and non-modifiable risk factors.
But what actually was the reason that in the present guidelines, as compared to the past, we have now moved away from the pure glucosecentric approach to the therapy of type 2 diabetes, more to risk stratification approach. And what is missing, coming back to the question, is definitely the cardiovascular risk stratification. In talking type 2 diabetes, that should be definitely included.
One thing that I found striking is when I looked at the patient characteristics, I saw that-- I even took a note-- 52% were on metformin, plus a sulfonylurea. And as far as I recall, it was about the aim. And research question was about second and third choice. So maybe it would have been better if not more than half would have been on two drugs already. That is one thing.
And the other thing is I've heard during the discussion that the TriMaster study was designed in 2015, I think. And of course, at that time, guidelines were including other recommendations because we weren't at the state level of best research evidence about the drugs we have available for the therapy of type 2 diabetes. We are today.
One thing that I think is very important is when we think about our therapeutic approach to type 2 diabetes, the first thing that comes into our minds, of course, is to control the blood sugar levels. But when we look at the evidence in how far that surrogate translates into heart outcomes in terms of morbidity and mortality, we see that because this multimorbid condition, which actually affects a lot of organ systems.
The pure glycemic control approach is not enough. So the primary outcome here was change in A1C. And that is maybe, again, one limitation of the study because it's a quite old fashioned pure glucosecentric approach to the management of type 2 diabetes.
In terms of patient-centeredness, I said that family physicians general practitioners, due to the core competencies and the general principles of the discipline, have a very patient-centered approach. And when we look at this patient preference part of the results, we see the drug which has the least side effects still has the highest rate of dropout.
So these things need to be looked into a little bit more in detail. And that's why I said I believe the results of this planned qualitative study will be so crucial for our understanding. Which drug is the best one for this person at this moment in her or his clinical situation and with her presentation and reason for encounter today? Will she or he be responder, a non-responder, a tier, persister? These things we need to figure out a little bit more in detail. And for this qualitative study is, I think, definitely crucial.