Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study

• Published in: Clinical therapeutics 2006-10, Vol.28 (10), p.1556-1568
• Main Authors: Rosenstock, Julio, Brazg, Ronald, Andryuk, Paula J., Lu, Kaifeng, Stein, Peter
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Cholesterol; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucagon; Glucose; Hormones; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Insulin resistance; Laboratories; Male; Medical sciences; Metabolism; Middle Aged; Peptides; Pharmacology. Drug treatments; Placebos; Protease Inhibitors - administration & dosage; Protease Inhibitors - adverse effects; Protease Inhibitors - therapeutic use; Pyrazines - administration & dosage; Pyrazines - adverse effects; Pyrazines - therapeutic use; Sitagliptin Phosphate; Treatment Outcome; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - therapeutic use
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2006.10.007

The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control (glycosylated hemoglobin [HbA 1c] ≥7% and ≤10%) while receiving a stable dose of pioglitazone. This was a 24-week, multicenter, ran domized, double-blind, placebo-controlled, parallel group study in patients aged ≥18 years (ClinicalTrials. gov NCT00086502). At screening, all patients began a diet/exercise program that continued throughout the study period. Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period. Patients with an HbA 1c ≥7% and ≤10% at the end of this period entered a 2-week, single-blind, placebo run-in period (total duration of run-in period, up to 21 weeks). Patients who had been receiving pioglitazone monotherapy (30 or 45 mg/d) and had an HbA 1c ≥7% and ≤10% entered the 2-week, single-blind, placebo run-in period directly. Thus, at the time of randomization, all patients were receiving ongoing pioglitazone (30 or 45 mg/d). Patients were randomized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks. The primary efficacy end point was the change from baseline in HbA 1c at week 24. Secondary efficacy end points included the change from baseline in fasting plasma glucose (FPG), insulin, and proinsulin; the Homeostasis Model Assessment β-cell function and insulin-resistance indexes; the proinsulin/ insulin ratio; the Quantitative Insulin Sensitivity Check Index; the percent changes from baseline in selected lipid parameters; the proportion of patients meeting the American Diabetes Association HbA 1c, goal of