Multiple-dose administration of alogliptin to patients with type 2 diabetes also resulted in a peak inhibition of DPP-4 within one to two hours and exceeded 93% across all doses (25 mg, 100 mg and 400 mg) after a single dose and after 14 days of once-daily dosing). At these doses of alogliptin, inhibition of DPP-4 remained above 81% at 24 hours after 14 days of dosing.

Pioglitazone

Clinical studies demonstrate that pioglitazone improves insulin sensitivity in insulin-resistant patients. Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves hepatic sensitivity to insulin. In patients with type 2 diabetes, the decreased insulin resistance produced by pioglitazone results in lower plasma glucose concentrations, lower plasma insulin concentrations and lower A1C values. In controlled clinical trials, pioglitazone had an additive effect on glycemic control when used in combination with a sulfonylurea, metformin or insulin [see Clinical Studies (14)]. Patients with lipid abnormalities were included in clinical trials with pioglitazone. Overall, patients treated with pioglitazone had mean decreases in serum triglycerides, mean increases in HDL cholesterol and no consistent mean changes in LDL and total cholesterol. There is no conclusive evidence of macrovascular benefit with pioglitazone or any other antidiabetic medication [see Warnings and Precautions (5.11) and Adverse Reactions (6.1)].
In a 26-week, placebo-controlled, dose-ranging monotherapy study, mean serum triglycerides decreased in the pioglitazone 15 mg, 30 mg and 45 mg dose groups compared to a mean increase in the placebo group. Mean HDL cholesterol increased to a greater extent in patients treated with pioglitazone than in the placebo-treated patients. There were no consistent differences for LDL and total cholesterol in patients treated with pioglitazone compared to placebo (Table 7).
Table 7. Lipids in a 26-Week, Placebo-Controlled, Monotherapy, Dose-Ranging Study
 
 Placebo
 Pioglitazone 15 mg Once Daily
 Pioglitazone 30 mg Once Daily
 Pioglitazone 45 mg Once Daily
 
Triglycerides (mg/dL)
 N=79
 N=79
 N=84
 N=77
 
Baseline (mean)
 263
 284
 261
 260
 
Percent change from baseline (adjusted mean *)
 4.8%
 -9%†
 -9.6%†
 -9.3%†
 
HDL Cholesterol (mg/dL)
 N=79
 N=79
 N=83
 N=77
 
Baseline (mean)
 42
 40
 41
 41
 
Percent change from baseline (adjusted mean *)
 8.1%
 14.1%†
 12.2%
 19.1%†
 
LDL Cholesterol (mg/dL)
 N=65
 N=63
 N=74
 N=62
 
Baseline (mean)
 139
 132
 136
 127
 
Percent change from baseline (adjusted mean *)
 4.8%
 7.2%
 5.2%
 6%
 
Total Cholesterol (mg/dL)
 N=79
 N=79
 N=84
 N=77
 
Baseline (mean)
 225
 220
 223
 214