domized, double-blind, placebo-controlled study designed to assess the efficacy of sitagliptin in combination with metformin. Patients already on metformin (N=431) at a dose of at least 1500 mg per day were randomized after completing a 2-week single-blind placebo run-in period. Patients on metformin and another antihyperglycemic agent (N=229) and patients not on any antihyperglycemic agents (off therapy for at least 8 weeks, N=41) were randomized after a run-in period of approximately 10 weeks on metformin (at a dose of at least 1500 mg per day) in monotherapy. Patients with inadequate glycemic control (A1C 7% to 10%) were randomized to the addition of either 100 mg of sitagliptin or placebo, administered once daily. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue.
In combination with metformin, sitagliptin provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo with metformin (Table 8). Rescue glycemic therapy was used in 5% of patients treated with sitagliptin 100 mg and 14% of patients treated with placebo. A similar decrease in body weight was observed for both treatment groups.
Table 8 Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin in Add-on Combination Therapy with Metformin * Sitagliptin 100 mg + Metformin Placebo +
Metformin
*
Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy.
†
Least squares means adjusted for prior antihyperglycemic therapy and baseline value.
‡
p<0.001 compared to placebo + metformin.
A1C (%) N = 453 N = 224
Baseline (mean) 8.0 8.0
Change from baseline (adjusted mean†) -0.7 -0.0
Difference from placebo + metformin (adjusted mean†) (95% CI) -0.7‡
(-0.8, -0.5)
Patients (%) achieving A1C <7% 213 (47%) 41 (18%)
FPG (mg/dL) N = 454 N = 226
Baseline (mean) 170 174
Change from baseline (adjusted mean†) -17 9
Difference from placebo + metformin (adjusted mean†) (95% CI) -25‡
(-31, -20)
2-hour PPG (mg/dL) N = 387 N = 182
Baseline (mean) 275 272
Change from baseline (adjusted mean†) -62 -11
Difference from placebo + metformin (adjusted mean†) (95% CI) -51‡
(-61, -41)
Initial Combination Therapy with Metformin
A total of 1091 patients with type 2 diabetes and inadequate glycemic control on diet and exercise participated in a 24-week, randomized, double-blind, placebo-controlled factorial study designed to assess the efficacy of sitagliptin as initial therapy in combination with metformin. Patients on an antihyperglycemic agent (N=541) discontinued the agent, and underwent a diet, exercise, and drug washout period of up to 12 weeks duration. After the washout period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized after completing a 2-week single-blind placebo run-in period. Patients not on antihyperglycemic agents at study entry (N=550) with inadequate glycemic control (A1C 7.5% to 11%) 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 placebo, 100 mg of sitagliptin once daily, 500 mg or 1000 mg of metformin twice daily, or 50 mg of sitagliptin twice |
