Advancing metrics and therapy in the card: using dTIR to assess outcomes for adults with Type 2 diabetes receiving an FRC
Thank you so much. Many thanks to some of you for kind invitation. My name is Martin Eluzick. I'm from the Diabetes Center of the Institute for Clinical and Experimental Medicine in Prague, Czech Republic. And it's really my pleasure having the very first Booth talk of this meeting. And the title of my presentation is Advancing metrics and therapy and care using derived time and range to assess outcomes for adults with type 2 diabetes receiving a fixed ratio combination. These are my disclosures and a disclaimer. This talk is sponsored by Sun Office. It's on Sun of the booth as you can see. So let me just move to the next slide. So the role of time and range and continuous glucose monitoring in type 2 diabetes. We all know that time and range is well established metrics in type 1 diabetes and that continuous glucose monitoring is now standard of care for patients with type 1 diabetes. And I'm sure you are all familiar with the concept. Time and range is the percentage of time when the patient has blood glucose within 3.9 to 10 millimos per liter or 70 to 180 milligrams per deciliter. And optimally, we want our patients to have the time and range for at least 70% of the time and range of the patient's health. And now we know that it's very difficult in some patients. We also know that the higher time and range is associated with many benefits both in patients with type 1 diabetes and also for patients with type 2 diabetes. So nevertheless, if you look at our population of patients with type 2 diabetes, only few of these patients actually have continuous glucose monitoring. And then when CGM data are not available, we can use the so-called derived time and range that can also provide very important insights. So, derived time and range is calculated from self-measured blood glucose measurements. And it's again defined as the proportion of SMBG measurements within target glucose range. Again, the target is as I mentioned before. Now, optimally, we should be using seven points, pre-end post breakfast, pre-end post lunch, pre-end post dinner, and bedtime measurement to calculate the derived time and range. Now, let me just come back a little bit to the clinical practice. So we know that achievement of glycemic targets in type 2 diabetes is often quite complicated, and we often need to intensify the treatment to achieve the goals. Now, the fixed ratio combination of basal insulin and GLP1 receptor agonist are recommended as a very high efficacy approach to glycemic management. Obviously, this is a perfect and complementary combination with basal insulin-improving fasting blood glucose, as you well know, and inhibiting hepatic glucose production and GLP1 receptor agonist really taking care of the post-prendial glucose. And as we all know, the post-prendial glucose management is equally as important as the fasting blood glucose management for the reducing glycemic variability and also improving the glucose control. Now, the fixed ratio combination of basal insulin and GLP1 receptor agonist is a very simple regimen, one injection per day. Therefore, it has many clinical benefits, such as improved glucose control, improved efficacy in controlling both fasting and post-prendial glucose. Importantly, it doesn't increase the risk of hypoglycemia as compared to basal insulin alone, and it has body weight benefits still decreasing body weight in majority of the patients. While we have the data supporting all these statements, the CGM timing range data for treatment and investment options in these kinds of patients with type 2 diabetes are limited. Therefore, we performed our analysis when we used the data from the LIXILAND program to look into the derive timing range in patients treated by the IGLA RIXIFX ratio combination and comparators. So, just to briefly remind you the LIXILAND program, which was the clinical program, which has been done to test the efficacy and safety of IGLA RIXIFX ratio combination. So, here we put together the free trials, LIXILAND O trial, which included insulin-nieve adults with type 2 diabetes, uncontrolled on the oral and to diabetic agents. And then they were randomized into IGLA RIXIFX plasma forming or insulin-glargin alone plus metformin or lixis-anatide alone plus metformin. Now, LIXILAND L trial included patients with type 2 diabetes, who were insufficiently controlled on basal insulin, and they were then randomized either to IGLA RIXIFX plus minus metformin or the titration of insulin-glargin plus minus metformin. Finally, the first trial were the data from the LIXILAND G trial, which included patients with type 2 diabetes, uncontrolled on oral and to diabetic agents plus glp1 receptor agonists either once daily or once weekly. And the patients were randomized into IGLA RIXI or the continuation of glp1 receptor agonist treatment. And the analysis of the derive-timing range here were performed or calculated using participant's seven-point SMBG profiles, and they also looked into derive-time above range and derive-time below range. So, this is the first set of data, and please focus on these three columns. So, this is the proportion of SMBG readings at derive-time in range, derive-time above range, and derive-time below range. And as you can see, with IGLA RIXIDAR was a significant increase in the proportion of patients, meaning that significantly more participants actually achieved derive-time in range, at least 70%. They also, the highest number of patients achieved at least 5% increase in derive-time in range. And finally, the highest proportion of patients on IGLA RIXIDAR achieved the triple target of derive-time in range, more than 70%. Derived-time below range, less than 4%, and derive-time above range, less than 25%. So, I think it's safe to conclude that the efficacy of IGLA RIXIDAR was higher than this of insulin-garging alone, lixicenotite alone, or other glp1 receptor agonist alone. And here, we are coming to Lixil and L, SAPANALISIS, which was basically switching to IGLA RIXIDAR from insulin-glarging. And here, you can see that with the IGLA RIXIDAR was a significant increase in the proportion of SMBG, being within derive-time in range. And you can see that, again, look at at least 70% values in time in range. It should be 70 to 180 here. You can see that it was achieved in 66% of participants with IGLA RIXIDAR as compared to 52% on insulin-garging alone. More patients had at least 5% improvement in the derive-time in range, and the same people target combination of derive-time in range of about 70% derive-time below range, below 4% and derive-time above range, less than 25%. Significantly, more patients with IGLA RIXIDAR as compared to insulin-garging. So, ladies and gentlemen, let me summarize my presentation. The time in range data may certainly provide more actionable information versus the, I should say, old gold standard, HBM1C. I think we have enough data to say that in patients with type 1 diabetes, but I think we are getting more and more data to say that also in patients with type 2 diabetes. In the absence of CGM data, the calculation of derive-time in range in an analysis of the LIXN program showed higher derive-time in range with IGLA RIXIDAR CIFIX ratio combination versus basal insulin or daily, weekly, GLP1 receptor agonist regimens. And certainly, we would very much welcome and we should perform future studies that will be using time in range data from continuous glucose monitoring optimally to validate these findings and the value of time in range as a glycemic metric for type 2 diabetes. And I'm happy to say that there are a couple of trials coming up where we will have the CGM data, so I do hope to be able to present you with some novel data, perhaps on next year's EASD or some other occasions. Many thanks for coming and thank you very much for your attention. And I will be happy to take the questions if there are any.
