g 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 during the study were treated with glipizide (or other sulfonylurea) rescue. The primary time point for eva luation of glycemic parameters was Week 18.
In combination with metformin and rosiglitazone, sitagliptin provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo with metformin and rosiglitazone (Table 13) at Week 18. At Week 54, mean reduction in A1C was -1.0% for patients treated with sitagliptin and -0.3% for patients treated with placebo in an analysis based on the intent-to-treat population. Rescue therapy was used in 18% of patients treated with sitagliptin 100 mg and 40% of patients treated with placebo. There was no significant difference between sitagliptin and placebo in body weight change.
Table 13 Glycemic Parameters at Week 18 for Sitagliptin in Add-on Combination Therapy with Metformin and Rosiglitazone * Sitagliptin 100 mg + Metformin + Rosiglitazone Placebo + Metformin + Rosiglitazone
*
Intent-to-treat population using last observation on study prior to glipizide (or other sulfonylurea) rescue therapy.
†
Least squares means adjusted for prior antihyperglycemic therapy status and baseline value.
‡
p<0.001 compared to placebo + metformin + rosiglitazone.
A1C (%) N = 176 N = 93
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