afety of TRADJENTA monotherapy. In both monotherapy studies, patients currently on an antihyperglycemic agent discontinued the agent and underwent a diet, exercise, and drug washout period of about 6 weeks that included an open-label placebo run-in during the last 2 weeks. Patients with inadequate glycemic control (A1C 7% to 10%) after the washout period were randomized; patients not currently on antihyperglycemic agents (off therapy for at least 8 weeks) with inadequate glycemic control (A1C 7% to 10%) were randomized after completing the 2-week open-label placebo run-in period. In the 18-week study, only patients ineligible for metformin were recruited. In the 18-week study, 76 patients were randomized to placebo and 151 to linagliptin 5 mg; in the 24-week study 167 patients were randomized to placebo and 336 to linagliptin 5 mg. Patients who failed to meet specific glycemic goals during the 18-week study received rescue therapy with pioglitazone and/or insulin; metformin rescue therapy was used in the 24-week trial.
Treatment with TRADJENTA 5 mg daily provided statistically significant improvements in A1C, FPG, and 2-hour PPG compared with placebo (Table 4). In the 18-week study, 12% of patients receiving TRADJENTA 5 mg and 18% who received placebo required rescue therapy. In the 24-week study, 10.2% of patients receiving TRADJENTA 5 mg and 20.9% of patients receiving placebo required rescue therapy. The improvement in A1C compared with placebo was not affected by gender, age, race, prior antihyperglycemic therapy, baseline BMI, or a standard index of insulin resistance (HOMA-IR). As is typical for trials of agents to treat type 2 diabetes, the mean reduction in A1C with TRADJENTA appears to be related to the degree of A1C elevation at baseline. In these 18- and 24-week studies, the changes from baseline in A1C were -0.4% and -0.4%, respectively, for those given TRADJENTA, and 0.1% and 0.3%, respectively, for those given placebo. Change from baseline in body weight did not differ significantly between the groups.
Table 4 Glycemic Parameters in Placebo-Controlled Monotherapy Studies of TRADJENTA* 18-Week Study 24-Week Study
TRADJENTA 5 mg Placebo TRADJENTA 5 mg Placebo
*Full analysis population using last observation on study
A1C (%)
Number of patients n = 147 n = 73 n = 333 n = 163
Baseline (mean) 8.1 8.1 8.0 8.0
Change from baseline (adjusted mean) -0.4 0.1 -0.4 0.3
Difference from placebo (adjusted mean) (95% CI) -0.6 (-0.9, -0.3) -0.7% (-0.9, -0.5)
Patients (%) achieving A1C <7% 41 (28%) 11 (15%) 77 (25%) 17 (12%)
FPG (mg/dL)
Number of patients n = 138 n = 66 n = 318 n = 149
Baseline (mean) 178.4 175.6 164 166
Change from baseline (adjusted mean) -13.3 7.2 -8.5 14.8
Difference from placebo (adjusted mean) (95% CI) -20.5 (-31.1, -9.9) -23.3 (-30.4, -16.3)
2-hour PPG (mg/dL)
Number of patients Data not available Data not available n = 67 n = 24
Baseline (mean) 258 244
Change from baseline (adjusted mean) -33
