After 52 weeks, linagliptin and glimepiride both had reductions from baseline in A1C (-0.4% for linagliptin, -0.6% for glimepiride) from a baseline mean of 7.7% (Table 6). The mean difference between groups in HbA1c change from baseline was 0.2% with 2-sided 97.5% confidence interval (0.1%, 0.3%) for the intent-to-treat population using last observation carried forward. These results were consistent with the completers analysis.

Patients treated with linagliptin exhibited a significant mean decrease from baseline body weight compared to a significant weight gain in patients administered glimepiride (-1.1 kg vs +1.4 kg, p< 0.0001).

Table 6 Glycemic Parameters at 52 Weeks in Study Comparing TRADJENTA to Glimepiride as Add-On Therapy in Patients Inadequately Controlled on Metformin**   TRADJENTA 5 mg + Metformin Glimepiride + Metformin
(mean Glimepiride dose 3 mg)
*p<0.0001 vs glimepiride
**Full analysis population using last observation on study
A1C (%)    
Number of patients n = 766  n = 761 
Baseline (mean)  7.7 7.7
Change from baseline (adjusted mean)  -0.4 -0.6
Difference from glimepiride (adjusted mean) (97.5% CI)  -- 0.2 (0.1, 0.3)
FPG (mg/dL)    
Number of patients n = 736  n = 731 
Baseline (mean)  164.1 166.6
Change from baseline (adjusted mean)  -8.6 -16.2
Hypoglycemia incidence (%)    
Number of patients n = 778 N = 781
Incidence 5.4* 31.8

Add-On Combination Therapy with Pioglitazone
A total of 389 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 pioglitazone. Therapy was stopped in patients on oral antihyperglycemic therapy for a period of 6 weeks (4 weeks followed by a 2-week open-label placebo run-in period). Drug-naïve patients entered directly in to the 2-week placebo run-in period. After the run-in period patients were randomized to receive either linagliptin 5 mg or placebo, both in addition to pioglitazone 30 mg daily. Patients who failed to meet specific glycemic goals during the studies were treated with metformin rescue. Glycemic endpoints measured were A1C and FPG.

In initial combination with pioglitazone 30 mg, linagliptin 5 mg provided statistically significant improvements in A1C and FPG compared to placebo with pioglitazone (Table 7). Rescue therapy was used in 7.9% of patients treated with linagliptin 5 mg/pioglitazone 30 mg and 14.1% of patients treated with placebo/pioglitazone 30 mg. Patient weight increased in both groups during the study with an adjusted mean change from baseline of 2.3 kg and 1.2 kg in the linagliptin 5 mg/pioglitazone 30 mg and placebo/pioglitazone 30 mg groups, respectively (p = 0.0141).

Table 7 Glycemic Parameters in Placebo-Controlled Study for TRADJENTA in Combination Therapy with Pioglitazone*   TRADJENTA 5 mg + Pioglitazone  Placebo + Pioglitazone
*Full analysis population using last observation on study
A1C (%)     
Number of patients n = 252  n