123-LB: The Simplici-T1 Trial: Relationship between Glycemic Control and Insulin Dose

Abstract

The Simplici-T1 trial (NCT03335371), designed to explore the safety and efficacy of TTP399 as an oral adjunctive therapy for T1DM, showed that addition of TTP399 to an optimized insulin regimen produced a statistically significant improvement in HbA1c (-0.32%, p<0.01) and Daytime Time In Range (8%, p<0.05) relative to placebo. The treat-to-target (FPG: ~80-130mg/dL; post meal glucose: <180-200 mg/dL) design of the study allowed changes in insulin dose after the insulin-optimization period. To evaluate the effect that these changes could have on A1c, several pre-planned analyses were performed. A positive correlation was observed between reduction in A1c and both reduction in total insulin (p=0.008) (Figure 1) and bolus insulin dose (p=0.004) in the TTP399-treated group but not in the PBO group. A subgroup analysis, matching on changes in insulin use reveals that, relative to PBO, those treated with TTP399 who maintained the optimized insulin regimen improved A1c by -0.35%, p=0.04 (41%TTP399; 36% PBO). The group that reduced their total insulin dose by more than 0.06U/Kg (i.e.,>10% reduction in total and >20% reduction in bolus insulin dose; 47% TTP399; 33% PBO) improved A1c by -0.41%, p=0.013. These improvements occurred without increasing ketones in plasma or hypoglycemic events. During the 12-week treatment period, 12% of the TTP399 group and 31%of the PBO increased their insulin dose. Disclosure C. Valcarce: Employee; Self; vTv Therapeutics. J.L. Freeman: Employee; Self; vTv Therapeutics. Stock/Shareholder; Self; vTv Therapeutics. Stock/Shareholder; Spouse/Partner; vTv Therapeutics. I. Dunn: None. K. Klein: None. J.B. Buse: Consultant; Self; Cirius Therapeutics, CSL Behring, Neurimmune. Research Support; Self; American Diabetes Association, National Institutes of Health, Novo Nordisk A/S, Patient-Centered Outcomes Research Institute, Sanofi, Tolerion, Inc., vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings, Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg Therapeutics, Novo Nordisk A/S, Senseonics, Inc, vTv Therapeutics, Zafgen, Inc. Funding JDRF; vTv Therapeutics; National Institutes of Health (UL1TR002489)