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- Title
Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function.
- Authors
Alba, M.; Ahrén, B.; Inzucchi, S. E.; Guan, Y.; Mallick, M.; Xu, L.; O'Neill, E. A.; Williams‐Herman, D. E.; Kaufman, K. D.; Goldstein, B. J.
- Abstract
Aims The effects of sitagliptin and pioglitazone, alone and in combination, on α- and β-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 (1 :1 :1 : 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. Φs, a measure of dynamic β-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 β-cell function and insulin sensitivity, improved with all active treatments versus placebo. Conclusions Sitagliptin and pioglitazone enhanced β-cell function (increasing postmeal Φs), 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.
- Subjects
SITAGLIPTIN; PIOGLITAZONE; ISLANDS of Langerhans; GLUCOSE; CELL physiology; PEOPLE with diabetes; BLOOD sugar; PLACEBOS
- Publication
Diabetes, Obesity & Metabolism, 2013, Vol 15, Issue 12, p1101
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/dom.12145