Effectiveness and saftey of iGlarLixi in adults with T2D- results from the real - world study CHANCE
Hello and welcome, dear colleagues, to this booth doc at the Sanofi booth. Welcome to my presentation on the chance trial. I'd like to share some data with you on a real world evidence trial, the chance trial. My name is Yohng Soifat. I'm from Germany actually here in the southern part of Germany and from Freiburg. University Hospital of Freiburg, I'm head of the division of Endocrinology and Dibotology at the University Hospital in Freiburg. So effectiveness and safety of Eichlar, Lixi in adults with type 2 diabetes, real world study chance. I show you my disclosures, which I'm happy to share. And also some homework here, the disclaimer. So it's quite obvious that this is a Sanofi booth talk, so the talk is sponsored by Sanofi, obviously. But I'd like to start out with a patient, 65-year young, John, type 2 diabetes, 12-year history, HBA1C above 8.5%. BMR, high BMI, elevated fasting, plasma glucose is on metformin, amputlyflosin, and insulin larchine once a day, 40 units, so basal oral therapy. And he has an HBA1C of 8.5. It's overweight, so there are some choices here with respect to escalation of therapy. So what choices would we consider, premixed insulin regimen, basal bolus insulin regimen with intensified insulin therapy, addition of a GLP1 receptor agonist, or switch to a fixed ratio combination of basal insulin plus GLP1 receptor agonist, or other what kind of, are there any proposals on your side? I think the GLP1 receptor agonist would also be a good choice here, right? The patient is overweight, not a target. Of course, insulin larchine, we don't know whether it can be more intensified to dose, but maybe for the purpose of this talk, we dive a little bit more into this fixed ratio combination thought with this patient. So of course, there are thresholds and thoughts when we intensify therapy with respect to glycemic control, hypoglycemia, weight gain, adverse events, burden, and adherence. And why these fixed ratio combinations could be maybe an attractive thing to do when we escalate therapy, maybe they could address some of these barriers to escalation which were addressed above here. So as you know, that lixicenotide in the fixed ratio combination with insulin larchine, the eyclar lixi preparation, so likewise you can read here, has been tested or has been clinically developed in different trials, the lixilan O in insulin naive patients, then adults with type 2 diabetes, not very well controlled. On basal insulin, the lixilan L and the lixilan T patients who had already HLP1 receptor agonist a priori. For the purpose of this talk, the lixilan L trial and for the patient case, of course, this would be the relevant trial here. And what this trial showed is that the primary endpoint, the HBA1C, was lower in the fixed ratio combination as opposed to the larchine group here, body weight went down as opposed to the little increase with larchine. So at least we have maybe a weight neutral effect here with the addition of the HLP1 receptor agonist and the hypoglycemia rate was not quite different here if at all it was a little bit lower. So the chance trial is a real world evidence trial in, it has been done that we pursued in Germany in practices, so it was set up to look for the effectiveness and safety of ichlar lixi in people with type 2 diabetes, not a target on basal insulin plus oral anti-diabetic drugs. It was prospectively a prospective trial and it was done in Germany, ichlar lixi and there were baseline 12 weeks and 24 weeks time points when we looked at the efficacy and safety of ichlar lixi. This is the baseline demographics here. We had the full analysis set for you just to explain here the different groups. The full analysis set 70 patients, then a subgroup in this full analysis set of patients who did flash glucose monitoring or continuous glucose monitoring back then flash glucose monitoring and patients who had self measurement blood glucose. As you see around 60 years overweight BMI high, diabetes duration between 11 and 14 years elevated fasting plasma glucose is average HPA1C8.5. The individual target HPA1C just below 7, the individual target HPA1C was to be addressed by the treating physician by himself or herself. They should in the trial they should say okay this is the individual target for the patient because it was a non-interventional trial and just the data were reported prospectively. This is a graph showing the concomitant medication in this trial, the OAD use. What you see is of course most of it is metformin but also a substantial number of SGLT2 inhibitors and DPP4 inhibitors. What you can see is that the proportion of patients from baseline at switch means that switch from their baseline to IGLR-Lixi and then 12 weeks and 24 weeks consistently the proportion of patients who had no OAD increased over time and the patients who had less, a smaller number of OADs decreased over time. This was due to the effect of the IGLR-Lixi especially when we look at the DPP4 inhibitor use of course it doesn't make sense to continue a DPP4 inhibitor when you introduce a GRP1 receptor agonist in the treatment regimen in the combination therapy. The IGLR-Lixi dose change from baseline you see here 12 weeks and 24 weeks so around 10 to 11 units IGLR-Lixi dose change we saw in this analysis and not much difference between the groups and now you see the HBA1C change from baseline 12 weeks and 24 weeks what you may appreciate is that in the group or overall 0.6 to 0.7 HBA1C decrease here what you can see is in the group and we can discuss that the FGM group it took longer basically until they reached the end point of their HBA1C reduction and then we did an analysis with respect to timing range so on the left hand side you need to it is the so-called derived timing range from SMPG patients from blood glucose values and on the right side you see the patient in the timing range who did FGM and what you can appreciate is that at 24 weeks almost all patients were above 70% of both with derived timing range and real time measured time in range so patients benefited from the switch to the IGLR-Lixi therapy here with respect to timing range both increased and the similar patterns for SMPG derived time in range and FGM derived time in range fasting plasma glucose again went down about to 30 to 40 milligram per day by 30 to 40 milligram per deciliter a little less in the group with FGM users but they also had a baseline lower fasting plasma glucose so you know the higher you start out the larger the drop will be with respect to fasting plasma glucose also with HBA1C in patients I think that's a general theme in most of the most of the trials that may be due to that fact body weight change you see in the full analysis said that the weight change was around 3 kilograms and a little more in the FGM group a little less in the SMPG group so the GOP1 receptor agonist part or partner in this fixed ratio combination did what we would expect from it so at least with the despite the fact that we titrated up the insulin clarkine of course by 11 units as you saw before patients still due to the probably due to the GOP1 receptor agonist effect lost weight which is I think a option for escalation of therapy if you have a patient the patient in mind which I showed you right from the beginning with respect to hypoglycemia I think there's no need to really dive very deeply into it because the overall frequency of hypoglycemia both ADL level 1, ADL level 2 or even severe hypoglycemia was very very low and also the adverse event frequency was very low so with this switch from basal insulin to the fixed ratio combination we do not introduce a higher risk of hypoglycemia in these patients so to summarize that in this real world evidence trial chance treatment intensification from a basal oral therapy improved HBA1C time in range and fasting plasma glucose levels and the change in body weight is of course a favorable aspect when we switch from basal insulin to this fixed ratio combination hypoglycemia was not an issue in this trial and basically this real world evidence the performance of this medication fixed ratio combination in real world evidence or in real world was similar to that what has been seen in prospective randomized control trials such as the Lixilin study so I bring up the patient case in the last slide again so maybe we could think or discuss about using or thinking about the switch from insulin clarkin to this fixed ratio combination in this patient maybe we could also think about adding a GOP1 receptor agonist separately to this treatment intensification I think it's clear that treatment intensification in this patient needs to be done based on this parameters and I hope I could show you that maybe a fixed ratio combination could be a good option in this case and thereby I thank you very much for listening.
