Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on C-peptide kinetics.
Clin Pharmacol Drug Dev
; 4(1): 12-7, 2015 01.
Article
em En
| MEDLINE
| ID: mdl-27127999
ABSTRACT
Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves indices of ß-cell function estimated based on circulating C-peptide and glucose concentrations (e.g., Homeostasis Model Assessment [HOMA2-%B], meal tolerance test-based indices). However, use of these ß-cell function indices assumes C-peptide kinetics are not altered by canagliflozin. This 2-period crossover study assessed the effect of a single canagliflozin 300-mg dose on C-peptide kinetics in 10 healthy participants. Two hours after receiving canagliflozin or placebo, participants received intravenous somatostatin infusion to suppress endogenous C-peptide secretion and 1 hour later received a bolus injection of synthetic human C-peptide 150 µg. Serum C-peptide was measured over 3 hours and urinary glucose and C-peptide excretion were measured. C-peptide kinetic parameters, including total clearance (CLtotal ) and renal clearance (CLrenal ), were calculated. Serum C-peptide profiles were similar following canagliflozin or placebo treatment. C-peptide CLtotal was slightly lower with canagliflozin versus placebo (mean (SD) of 190 (37) vs. 197 (30) mL/min; canagliflozin/placebo ratio [90% CI] = 96.1% [93.0%; 99.3%]). Other kinetic parameters, including CLrenal , were generally similar between treatments. Results indicate canagliflozin 300 mg does not meaningfully alter C-peptide clearance or other kinetic parameters; therefore, C-peptide-based measurements of insulin secretion are appropriate for assessing ß-cell function in canagliflozin-treated participants.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeo C
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Células Secretoras de Insulina
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Canagliflozina
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Inibidores do Transportador 2 de Sódio-Glicose
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Hipoglicemiantes
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Túbulos Renais
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article