ADO09, a co-formulation of the amylin analogue pramlintide and the insulin analogue A21G, lowers postprandial blood glucose versus insulin lispro in type 1 diabetes.
Diabetes Obes Metab
; 23(4): 961-970, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33336850
ABSTRACT
AIM:
To compare the safety, pharmacokinetics and pharmacodynamics of ADO09 with insulin lispro (Lispro) and separate subcutaneous injections of human insulin and pramlintide (Ins&Pram) in 24 subjects with type 1 diabetes.METHODS:
At three dosing visits, participants received single doses of ADO09, Ins&Pram or Lispro immediately before eating a standardized mixed meal together with 1 g of acetaminophen, which was used as a surrogate marker to evaluate the kinetics of gastric emptying. Premeal blood glucose was adjusted to 126 mg/dL ± 10% by means of insulin and glucose infusions. The insulin dose was 7.5 U and the pramlintide dose was 45 µg. Blood glucose, glucagon and acetaminophen concentrations were assessed as pharmacodynamic endpoints; insulin and pramlintide concentrations were analysed as pharmacokinetic endpoints, and safety and tolerability were assessed.RESULTS:
Compared with Lispro, ADO09 reduced postprandial blood glucose (ppBG) excursions by more than 95% in the first hour postmeal (mean ± SD ∆AUC BG 0-1 h 1.4 ± 9.9 mg*h/dL vs. 43.5 ± 15.3 mg*h/dL; p < .0001). Maximum ppBG was significantly improved with ADO09 (∆BGmax 87.0 ± 35.5 mg/dL) versus both Lispro (109.2 ± 31.1 mg/dL; p = .0133) and Ins&Pram (109.4 ± 44.3 mg/dL; p = .0357). Gastric emptying with ADO09 was similar to Ins&Pram and significantly slower than with Lispro. All treatments were well tolerated and both adverse events and hypoglycaemic events were rare during the meal test procedure.CONCLUSION:
ADO09 was well tolerated and markedly reduced ppBG compared with Lispro. ADO09 formulation was generally similar to the separate administration of insulin and pramlintide, except for a better BG level in the 4-8 h interval postmeal. These positive results warrant further investigations with ADO09.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 1
/
Islet Amyloid Polypeptide
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Diabetes Obes Metab
Journal subject:
ENDOCRINOLOGIA
/
METABOLISMO
Year:
2021
Document type:
Article
Affiliation country:
Germany