witched to rosiglitazone ≥4mg/day) entered a dose-stable run-in period of 6 weeks. Patients on other dual therapy were switched to metformin ≥1500mg/day and rosiglitazone ≥4mg/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 100mg of sitagliptin or placebo, administered once daily. Patients who failed to meet specific glycemic goals during the studies 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 (Table7) at Week18. 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 100mg and 40% of patients treated with placebo. There was no significant difference between sitagliptin and placebo in body weight change.
Table 7: Glycemic Parameters at Week 18 for Sitagliptin in Add-on Combination Therapy with Metformin and 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.
Week 18
Sitagliptin 100mg + Metformin + Rosiglitazone Placebo +
Metformin + Rosiglitazone
A1C (%) N =176 N = 93
Baseline (mean) 8.8 8.7
Change from baseline (adjusted mean†) -1.0 -0.4
Difference from placebo + rosiglitazone + metformin (adjusted mean†) (95% CI) -0.7‡
(-0.9,-0.4)
Patients (%) achieving A1C <7% 39 (22%) 9 (10%)
FPG (mg/dL) N = 179 N =94
Baseline (mean) 181 182
Change from baseline (adjusted mean†) -30 -11
Difference from placebo + rosiglitazone + metformin (adjusted mean†) (95% CI) -18‡
(-26, -10)
2-hour PPG (mg/dL) N = 152 N = 80
Baseline (mean) 256 248
Change from baseline (adjusted mean†) -59 -21
Difference from placebo + rosiglitazone + metformin (adjusted mean†) (95% CI) -39‡
(-51, -26)
Sitagliptin Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled on the Combination of Metformin and Insulin
A total of 641patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of sitagliptin as add-on to insulin therapy. Approximately 75% of patients were also taking metformin. Patients entered a 2-week, single-blind run-in treatment period on pre-mixed, long-acting, or intermediate-acting insulin, with or without metformin (≥1500mg per day). Patients using short-acting insulins were excluded unless the short-acting insulin was administered as part of a pre-mixed insulin. After the run-in period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized to the addition of either 100mg of sitagliptin (N=229) or placebo (N=233), administered once daily. Patients were on
