Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function
| Autor: | M, Alba, B, Ahrén, S E, Inzucchi, Y, Guan, M, Mallick, L, Xu, E A, O'Neill, D E, Williams-Herman, K D, Kaufman, B J, Goldstein |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Blood Glucose C-Peptide Pioglitazone Sitagliptin Phosphate Middle Aged Triazoles Glucagon Postprandial Period Treatment Outcome Diabetes Mellitus Type 2 Double-Blind Method Glucagon-Secreting Cells Insulin-Secreting Cells Pyrazines Humans Hypoglycemic Agents Insulin Drug Therapy Combination Thiazolidinediones Aged |
| Zdroj: | Diabetes, obesitymetabolism. 15(12) |
| ISSN: | 1463-1326 |
| Popis: | The effects of sitagliptin and pioglitazone, alone and in combination, on α- and β-cell function were assessed in patients with type 2 diabetes.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.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 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.Sitagliptin and pioglitazone enhanced β-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. |
| Databáze: | OpenAIRE |
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