Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function.
Diabetes Obes Metab
; 15(12): 1101-10, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23782502
ABSTRACT
AIMS:
The effects of sitagliptin and pioglitazone, alone and in combination, on α- and ß-cell function were assessed in patients with type 2 diabetes.METHODS:
Following a 6-week diet/exercise period, 211 patients with HbA1c of 6.5-9.0% and fasting plasma glucose of 7.2-14.4 mmol/l were randomized (111 1) to sitagliptin, pioglitazone, sitagliptin + pioglitazone or placebo. At baseline and after 12 weeks, patients were given a mixed meal followed by frequent blood sampling for measurements of glucose, insulin, C-peptide and glucagon.RESULTS:
After 12 weeks, 5-h glucose total area under the curve (AUC) decreased in all active treatments versus placebo; reduction with sitagliptin + pioglitazone was greater versus either monotherapy. The 5-h insulin total AUC increased with sitagliptin versus all other treatments and increased with sitagliptin + pioglitazone versus pioglitazone. The 3-h glucagon AUC decreased with sitagliptin versus placebo and decreased with sitagliptin + pioglitazone versus pioglitazone or placebo. Φ(s), a measure of dynamic ß-cell responsiveness to above-basal glucose concentrations, increased with either monotherapy versus placebo and increased with sitagliptin + pioglitazone versus either monotherapy. The insulin sensitivity index (ISI), a composite index of insulin sensitivity, improved with pioglitazone and sitagliptin + pioglitazone versus placebo. The disposition index, a measure of the relationship between ß-cell function and insulin sensitivity, improved with all active treatments versus placebo.CONCLUSIONS:
Sitagliptin and pioglitazone enhanced ß-cell function (increasing postmeal Φ(s)), and sitagliptin improved α-cell function (decreasing postmeal glucagon) after 12 weeks in patients with type 2 diabetes. Through these complementary mechanisms of action, the combination of sitagliptin and pioglitazone reduced postmeal glucose more than either treatment alone.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazinas
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Triazóis
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Tiazolidinedionas
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Diabetes Mellitus Tipo 2
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Células Secretoras de Glucagon
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Células Secretoras de Insulina
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Hipoglicemiantes
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
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Aged
/
Humans
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article