Add-On Combination with Sulfonylureas
A total of 245 patients with type 2 diabetes participated in an 18-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of linagliptin in combination with sulfonylurea (SU). Patients on sulfonylurea monotherapy (n = 142) were randomized after completing a 2-week single-blind placebo run-in period. Patients on a sulfonylurea plus one additional oral antihyperglycemic agent (n = 103) were randomized after a wash-out period of 4 weeks and a 2-week single-blind placebo run-in period. Patients were randomized to the addition of linagliptin 5 mg or to placebo, each administered once daily. Patients who failed to meet specific glycemic goals during the studies were treated with metformin rescue. Glycemic endpoints measured included A1C and FPG.

In combination with a sulfonylurea, linagliptin provided statistically significant improvements in A1C compared with placebo following 18 weeks treatment; the improvements in FPG observed with linagliptin were not statistically significant compared with placebo (Table 8). Rescue therapy was used in 7.6% of patients treated with linagliptin 5 mg and 15.9% of patients treated with placebo. There was no significant difference between linagliptin and placebo in body weight.

Table 8 Glycemic Parameters at in Placebo-Controlled Study for TRADJENTA in Combination with Sulfonylurea*   TRADJENTA 5 mg + SU Placebo + SU
SU = sulfonylurea
*Full analysis population using last observation on study
A1C (%)     
Number of patients n = 158  n = 82 
Baseline (mean) 8.6 8.6
Change from baseline (adjusted mean) -0.5 -0.1
Difference from placebo + SU (adjusted mean) (95% CI)  -0.5 (-0.7, -0.2) --
Patients (%) achieving A1C <7%  15.2  3.7 
FPG (mg/dL)     
Number of patients n = 155  n = 78 
Baseline (mean)  180 171
Change from baseline (adjusted mean) -8.2 -1.8
Difference from placebo + SU (adjusted mean) (95% CI)  -6.4 (-17.2, 4.3) --

Add-On Combination Therapy with Metformin and a Sulfonylurea
A total of 1058 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of linagliptin in combination with a sulfonylurea and metformin. The most common sulfonylureas used by patients in the study were: glimepiride (31%), glibenclamide (26%), and gliclazide (26%, not available in the United States). Patients on a sulfonylurea and metformin were randomized to receive linagliptin 5 mg or placebo, each administered once daily. Patients who failed to meet specific glycemic goals during the study were treated with pioglitazone rescue. Glycemic endpoints measured included A1C and FPG.

In combination with a sulfonylurea and metformin, TRADJENTA provided