Once-weekly dulaglutide 1.5 mg restores insulin secretion in response to intravenous glucose infusion.
Diabetes Obes Metab
; 19(4): 517-523, 2017 04.
Article
in En
| MEDLINE
| ID: mdl-27976833
ABSTRACT
AIMS:
To evaluate the effects of dulaglutide 1.5 mg on first- and second-phase insulin secretion in response to an intravenous (i.v.) glucose bolus challenge, in subjects with type 2 diabetes mellitus (T2DM; primary objective) and in healthy subjects. MATERIALS ANDMETHODS:
In this randomized, double-blind, placebo-controlled, 2-period crossover study, subjects received a single subcutaneous injection of dulaglutide 1.5 mg or placebo on day 1 of each period. On day 3, subjects underwent a 6-hour insulin infusion, followed by an i.v. glucose bolus and a glucagon challenge during hyperglycaemia. Areas under the concentration-time curve and maximum concentrations for first- (AUC0-10 and Cmax0-10 ) and second-phase secretion (AUC10-180 and Cmax10-180 ) were calculated for insulin and C-peptide. The glucose disappearance constant (Kg ) and homeostasis model assessment of ß-cell function (HOMA-ß) were assessed.RESULTS:
In 20 subjects with T2DM, dulaglutide increased mean insulin AUC0-10 by 7.92-fold and Cmax0-10 by 5.40-fold vs placebo, and mean AUC10-180 and Cmax10-180 by 2.44- and 3.78- fold, respectively. In 10 healthy subjects, dulaglutide increased the mean insulin AUC0-10 by 3.09-fold and Cmax0-10 by 2.96-fold vs placebo, and mean AUC10-180 and Cmax10-180 by 2.04- and 4.15-fold, respectively. The corresponding C-peptide values also increased. Mean Kg and HOMA-ß were higher after dulaglutide compared with placebo.CONCLUSIONS:
In subjects with T2DM, a single dulaglutide 1.5-mg dose restored the first-phase insulin secretion in response to an i.v. glucose bolus, increased the second-phase insulin response and enhanced ß-cell function.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombinant Fusion Proteins
/
Immunoglobulin Fc Fragments
/
Diabetes Mellitus, Type 2
/
Glucagon-Like Peptides
/
Glucose
/
Hypoglycemic Agents
/
Insulin
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Diabetes Obes Metab
Journal subject:
ENDOCRINOLOGIA
/
METABOLISMO
Year:
2017
Document type:
Article