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
* Intent-to-treat population using last observation on study † Least squares means adjusted for treatment, baseline value, geographic region and baseline metformin dose ‡ Noninferior and statistically superior to metformin plus pioglitazone at the 0.025 one-sided significance level § p˂0.001 compared to 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‡ (-0.5, -0.3) -
% of Patients (n/N) achieving A1C ≤7% 33% (134/404)§ 21% (85/399)
FPG (mg/dL) N=399 N=396
Baseline (mean) 162 162
Change from Baseline (adjusted mean†) -15 -4
Difference from Pioglitazone 45 mg + Metformin (adjusted mean† with 95% confidence interval) -11§ (-16, -6) -
Alogliptin Add-On Therapy to a Thiazolidinedione

A 26 week, placebo-controlled study, was conducted to eva luate the efficacy and safety of alogliptin as add-on therapy to pioglitazone in patients with type 2 diabetes. A total of 493 patients inadequately controlled on a thiazolidinedione alone or in combination with metformin or a sulfonylurea (mean baseline A1C = 8%) were randomized to receive alogliptin 12.5 mg, alogliptin 25 mg or placebo. Patients were maintained on a stable dose of pioglitazone (median dose = 30 mg) during the treatment period and those who were also previously treated on metformin (median dose = 2000 mg) or sulfonylurea (median dose = 10 mg) prior to randomization were maintained on the combination therapy during the treatment period. All patients entered into a four-week, single-blind, placebo run-in period prior to randomization. Following randomization, all patients continued to receive instruction on diet and exercise. Patients who failed to meet prespecified hyperglycemic goals during the 26-week treatment period received glycemic rescue.

The addition of alogliptin 25 mg once daily to pioglitazone therapy resulted in significant improvements from baseline in A1C and FPG at Week 26 when compared to the addition of placebo (Table 13). A total of 9% of patients who were receiving alogliptin 25 mg and 12% of patients receiving placebo required glycemic rescue.

The improvement in A1C was not affected by gender, age, baseline BMI or baseline pioglitazone dose. The mean increase in body weight was similar between alogliptin and placebo when given in combination with pioglitazone. Lipid effects were neutral.

Table 13. Glycemic Parameters at Week 26 in a Placebo-Controlled Study of Alogliptin as Add-On Therapy to Pioglitazone*
Alogliptin 25 mg + Pioglitazone ± Metformin ± Sulfonylurea Placebo + Pioglitazone ± Metformin ± Sulfonylurea
* Intent-to-treat population using last observation on study † Least squares means adjusted for treatment, baseline value, geographic region