seline (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)
Add-on Combination Therapy with Glimepiride, with or without Metformin
A total of 441 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of sitagliptin in combination with glimepiride, with or without metformin. Patients entered a run-in treatment period on glimepiride (≥4 mg per day) alone or glimepiride in combination with metformin (≥1500 mg per day). After a dose-titration and dose-stable run-in period of up to 16 weeks and a 2-week placebo run-in period, patients with inadequate glycemic control (A1C 7.5% to 10.5%) 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 glimepiride, with or without metformin, sitagliptin provided significant improvements in A1C and FPG compared to placebo (Table 14). In the entire study population (patients on sitagliptin in combination with glimepiride and patients on sitagliptin in combination with glimepiride and metformin), a mean reduction from baseline relative to placebo in A1C of -0.7% and in FPG of -20 mg/dL was seen. Rescue therapy was used in 12% of patients treated with sitagliptin 100 mg and 27% of patients treated with placebo. In this study, patients treated with sitagliptin had a mean increase in body weight of 1.1 kg vs. placebo (+0.8 kg vs. -0.4 kg). In addition, there was an increased rate of hypoglycemia. [See Warnings and Precautions (5.5); Adverse Reactions (6.1).]
Table 14 Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin as Add-On Combination Therapy with Glimepiride, with or without Metformin * Sitagliptin 100 mg + Glimepiride Placebo + Glimepiride Sitagliptin 100 mg + Glimepiride + Metformin Placebo + Glimepiride + Metformin
*
Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy.
†
Least squares means adjusted for prior antihyperglycemic therapy status and baseline value.
‡
p<0.001 compared to placebo.
§
p<0.01 compared to placebo.
A1C (%) N = 102 N = 103 N = 115 N = 105
Baseline (mean) 8.4 8.5 8.3 8.3
Change from baseline (adjusted mean†) -0.3 0.3 -0.6 0.3
Difference from placebo (adjusted mean†) (95% CI) -0.6‡
(-0.8, -0.3) -0.9‡
(-1.1, -0.7)
Patients (%) achieving A1C <7% 11 (11%) 9 (9%) 26 (23%) 1 (1%)
FPG (mg/dL) N = 104 N = 104 N = 115 N = 109
Baseline (mean |
