In a 52-week, active-comparator study, a total of 803 patients inadequately controlled (mean baseline A1C = 8.2%) on a current regimen of pioglitazone 30 mg and metformin at least 1500 mg per day or at the maximum tolerated dose were randomized to either receive the addition of alogliptin 25 mg or the titration of pioglitazone 30 mg to 45 mg following a four-week, single-blind, placebo run-in period. Patients were maintained on a stable dose of metformin (median dose = 1700 mg). Patients who failed to meet prespecified hyperglycemic goals during the 52-week treatment period received glycemic rescue therapy.

In combination with pioglitazone and metformin, alogliptin 25 mg was shown to be statistically superior in lowering A1C and FPG compared with the titration of pioglitazone from 30 mg to 45 mg at Week 26 and Week 52 (Table 12, results shown only for Week 52). A total of 11% of patients who were receiving alogliptin 25 mg in combination with pioglitazone 30 mg and metformin and 22% of patients receiving a dose titration of pioglitazone from 30 mg to 45 mg in combination with metformin required glycemic rescue.

Improvements in A1C were not affected by gender, age, race or baseline BMI. The mean increase in body weight was similar in both treatment arms. Lipid effects were neutral.
Table 12. Glycemic Parameters at Week 52 in an Active-Controlled Study of Alogliptin as Add-On Combination Therapy to Metformin and Pioglitazone *
 
 Alogliptin 25 mg + Pioglitazone 30 mg + Metformin
 Pioglitazone 45 mg + Metformin
 
A1C (%)
 N=397
 N=394
 
Baseline (mean)
 8.2
 8.1
 
Change from Baseline (adjusted mean †)
 -0.7
 -0.3
 
Difference from Pioglitazone 45 mg + Metformin (adjusted mean † with 95% confidence interval)
 -0.4&Da