Grégory Meiffren, France
Adocia R&DPresenter of 1 Presentation
ADO09, A CO-FORMULATION OF PRAMLINTIDE AND INSULIN A21G IMPROVES POST-PRANDIAL GLUCOSE (PPG) VERSUS INSULIN ASPART IN TYPE 1 DIABETES (T1D)
Abstract
Background and Aims
Pramlintide improves PPG through delaying gastric emptying, reducing glucagon secretion, and promoting satiety. ADO09 is a stable co-formulation of pramlintide and insulin A21G under development. This double-blind, randomised, 2-period cross-over trial compared pre-meal ADO09 versus insulin aspart over 24 days in 28 T1D participants.
Methods
During a 28 days run-in period, basal insulin was switched to insulin degludec. The cross-over treatment periods consisted of 3 inpatient days (baseline assessments), followed by 3 outpatient weeks and a final inpatient mixed-meal-tolerance-test (MMTT) on day 24. Blood glucose, glucagonemia and kinetics of gastric emptying were analyzed, as were CGM-metrics. The two treatment periods were separated by a 5 to 7 day washout.
Results
Incremental plasma glucose AUCs during MMTT with ADO09 were reduced by >100% after 2h (p<0.001) and by 39% after 4h (not significant), gastric emptying was slower (Tmax +312%, p<0.0001) and glucagon suppressed by 78% over 0-2h (p<0.0001) versus insulin aspart. ADO09 showed improved CGM-metrics in the outpatient period with higher Time-In-Range (+51 min, p=0.01). Time <70 mg/dL was slightly higher (+9.6 min, p=0.046) as were hypoglycemic events (142 vs. 115). ADO09 reduced body weight (-0.7kg vs baseline, p=0.01). Mean daily ADO09 doses were lower than insulin aspart’s (17 vs 22 U, p<0.0001). Both treatments were well tolerated with more, but transient gastrointestinal adverse events (24 vs 6) with ADO09, consistent with the known side effect profile of pramlintide.
Conclusions
ADO09 was well tolerated and significantly improved post-prandial blood glucose control, CGM-metrics, weight control and bolus insulin needs versus insulin aspart over 24 days.