A total of 520 patients with type 2 diabetes and inadequate glycemic control on diet and exercise participated in a 24-week, randomized, double-blind study designed to assess the efficacy of sitagliptin as initial therapy in combination with pioglitazone. Patients not on antihyperglycemic agents at study entry (<4 weeks cumulative therapy over the past 2 years, and with no treatment over the prior 4 months) with inadequate glycemic control (A1C 8% to 12%) immediately entered the 2-week single-blind placebo run-in period and then were randomized. Approximately equal numbers of patients were randomized to receive initial therapy with 100 mg of sitagliptin in combination with 30 mg of pioglitazone once daily or 30 mg of pioglitazone once daily as monotherapy. There was no glycemic rescue therapy in this study.

Initial therapy with the combination of sitagliptin and pioglitazone provided significant improvements in A1C, FPG, and 2-hour PPG compared to pioglitazone monotherapy (Table 12). The improvement in A1C was generally consistent across subgroups defined by gender, age, race, baseline BMI, baseline A1C, or duration of disease. In this study, patients treated with sitagliptin in combination with pioglitazone had a mean increase in body weight of 1.1 kg compared to pioglitazone alone (3.0 kg vs. 1.9 kg).

Table 12: Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin in Combination with Pioglitazone as Initial Therapy*   Sitagliptin 100 mg + Pioglitazone Pioglitazone
*
Intent-to-treat population using last observation on study.
†
Least squares means adjusted for baseline value.
‡
p<0.001 compared to placebo + pioglitazone. 
A1C (%) N = 251 N = 246
  Baseline (mean) 9.5 9.4
  Change from baseline (adjusted mean†) -2.4 -1.5
  Difference from pioglitazone (adjusted mean†) (95% CI) -0.9‡
(-1.1, -0.7) 
  Patients (%) achieving A1C <7% 151 (60%) 68 (28%)
FPG (mg/dL)  N = 256 N = 253
  Baseline (mean) 203 201
  Change from baseline (adjusted mean†) -63 -40
  Difference from pioglitazone (adjusted mean†) (95% CI) -23‡
(-30, -15) 
2-hour PPG (mg/dL)  N = 216 N = 211
  Baseline (mean) 283 284
  Change from baseline (adjusted mean†) -114 -69
  Difference from pioglitazone (adjusted mean†) (95% CI) -45‡
(-57, -32) 

Add-on Combination Therapy with Metformin and Rosiglitazone

A total of 278 patients with type 2 diabetes participated in a 54-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of sitagliptin in combination with metformin and rosiglitazone. Patients on dual therapy with metformin ≥1500 mg/day and rosiglitazone ≥4 mg/day or with metformin ≥1500 mg/day and pioglitazone ≥30 mg/day (switched to rosiglitazone ≥4 mg/day) entered a dose-stable run-in period of 6 weeks. Patients on other dual therapy were switched to metformin ≥1500 mg/day and rosiglitazone ≥4 mg/day in a dose titration/stabilization run-in period of up to 20 weeks in duration. After the run-in period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized 2:1 to the addition of either 100 mg of sitagliptin or placebo, administered once daily. Patients who failed to meet specific glycemic goals duri