ADO09, A CO-FORMULATION OF THE AMYLIN-ANALOG PRAMLINTIDE AND THE A21G HUMAN INSULIN ANALOG, LOWERS POSTPRANDIAL BLOOD GLUCOSE VERSUS INSULIN LISPRO IN TYPE 1 DIABETES (T1D)
- Gregory Meiffren, France
- Gregory Meiffren, France
- Grit Andersen, Germany
- Cyril Seroussi, France
- Aymeric Ranson, France
- Susanne Famulla, Germany
- Martin Gaudier, France
- Rémi Soula, France
- Olivier Soula, France
- Rosy Eloy, France
- Tim Heise, Germany
- You-Ping Chan, France
- Richard Charvet, France
- Hans DeVries, Netherlands
Abstract
Background and Aims
Pramlintide, as an adjunct to insulin, improves postprandial blood glucose (ppBG) through delaying gastric emptying, reducing glucagon secretion, and promoting satiety. ADO09 is a co-formulation of pramlintide and a prandial insulin analog stable at pH 4. This double-blind, double-dummy, randomised, cross-over trial compared ADO09 with insulin lispro (LIS) and the separate injections of human insulin and pramlintide (Ins&Pram) in 24 patients with T1D.
Methods
At three dosing visits, participants received ADO09, Ins&Pram and LIS immediately before eating a standardised mixed meal (618 kcal, 53% carbohydrate, 19% protein, 26% fat, 2% fibers) and 1g paracetamol to evaluate the kinetics of gastric emptying. The insulin dose was 7.5 U and the pramlintide dose 45 µg.
Results
Compared with LIS, ADO09 reduced ppBG excursions by more than 95% over the first hour (p<0.0001), by 85% over 2h (p<0.0001) and 41% over 4h (p=0.0052) (Figure). With ADO09, gastric emptying was significantly slower than with LIS (Tmax_paracetamol 2.30±1.49 h vs 0.76±0.73 h, p<0.0001); and endogenous glucagon secretion was inhibited compared to LIS (deltaAUC_glucagon_0-2h 4.2±2.8 vs 11.8±6.2 pmol*h/L, p<0.0001). The effects of ADO09 and Ins&Pram were similar. All treatments were well tolerated and both adverse events (3 with ADO09, 2 with Ins&Pram) and hypoglycaemic events (2 each with ADO09 and Ins&Pram) were rare during the meal test procedures.
Conclusions
ADO09 was well tolerated, had similar effects on gastric emptying and endogenous glucagon secretion as separate injections of Ins&Pram and markedly reduced ppBG compared to LIS. These positive results warrant further investigations with ADO09 for the treatment of T1D.