MedicalResearch.com Interview with:
Prof. Dr. Thomas Danne
Chief Physician Diabetology, Endocrinology and General Pediatrics and Clinical Researc
Kinder und Junden Krankenhaus
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The double-blind, placebo controlled, Phase 3 study known as inTandem2 randomized 782 adult patients from 99 sites in the EU and Israel with type 1 diabetes on insulin pump or multiple daily injection therapy who had an A1C level entering the study between 7.0% and 11.0%. The three-arm study evaluated two doses of sotagliflozin, 200mg and 400mg, each taken once daily before the first meal of the day, against placebo. Prior to randomization, insulin was optimized for all patients over a six-week period, with the objective of improving glycemic control using insulin alone. After completion of this optimization period, patients were maintained on optimized insulin and randomized to one of two doses of sotagliflozin or placebo, and their baseline, post-optimization A1C was measured.
The mean baseline A1C levels after the six-week optimization period were 7.8%, 7.7% and 7.7% for patients randomized to the placebo, 200mg and 400mg arms, respectively (A1C was 8.4% across all dose arms prior to insulin optimization).
The primary endpoint of the study was change in A1C from baseline after a 24-week period of treatment. The trial has a double-blind long term extension of 28 weeks, with a total treatment duration of 52 weeks. There were 258 patients in the placebo arm, 261 patients in the 200mg dose arm and 263 patients in the 400mg dose arm. The overall mean placebo-adjusted A1C reduction at week 24 was 0.36% in the 200mg dose arm (p<0.001) and 0.35% in the 400mg dose arm (p<0.001). In response to regulatory input, a secondary endpoint to measure “net clinical benefit” was defined for this study as the proportion of patients at week 24 who achieved the standard of care A1C goal of less than 7.0% without any episode of severe hypoglycemia or DKA. 15% of patients in the placebo arm, 32% in the 200 mg dose arm and 32% in the 400mg dose arm achieved this endpoint (p<0.001 for both treatment arms).
MedicalResearch.com: What should readers take away from your report?
Response: Insulin has been the standard of care for individuals with type 1 diabetes for nearly a century. This study was designed to see if additional benefit could be achieved in addition to what could be established through the optimized use of insulin.
This threshold was especially high but necessary to isolate the benefit that could be achieved with sotagliflozin over and above the optimized use of insulin alone. This study showed at 24 weeks, a statistically significant reduction in A1C with both dose arms beyond what could be achieved with optimized insulin alone. In addition, the net clinical benefit of achieving these A1C reductions is assessed as positive with greater than 2 times more patients on the 200 mg and 400 mg dose arms compared to placebo able to achieve the net clinical benefit endpoint at week 24 of A1C less than 7.0% without a single occurrence of severe hypoglycemia or DKA.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: These study results reflect week 24 topline data. The complete study will continue to 52 week in duration and will include results such as the effect on body weight, blood pressure, and continuous glucose monitoring data to provide time in range data.
MedicalResearch.com: Is there anything else you would like to add?
Response: This study represents the second successful Phase 3 report for sotagliflozin as an oral anti-diabetic used as an adjunct to insulin therapy for type 1 diabetes. The study results showed that sotagliflozin provided additional statistically significant reductions in A1C levels beyond what could be established on optimized insulin. These A1C reductions were achieved with a positive net clinical benefit. There was a low rate of severe hypoglycemia and DKA during the study. During the 24-week study, rate of severe hypoglycemia was 2.7% in the placebo arm, 3.8% in the 200 mg dose arm and 2.3% in the 400 mg dose arm. The rate of DKA was 0.0% in the placebo arm, 0.4% in the 200 mg dose arm and 1.1% in the 400 mg dose arm during the same 24-week period.
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Citation: ADA2017 abstract
inTandem1 Study – “Twenty-Four Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes” (#69-OR)
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