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Trajenta
Linagliptin, 5 mg film coated tablet

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56.1% linagliptin), while 11.3% of patients in the placebo group and 13.6% of patients in the
linagliptin group were receiving sulphonylurea monotherapy.
Results
Superiority of linagliptin over placebo was demonstrated for the primary endpoint by a
treatment difference in HbAlc adjusted mean change from baseline of -0.59% (95% CI -0.88,
-0.29; p=0.0001) after 12 weeks. Sensitivity analyses confirmed the superiority of linagliptin.
Superiority of linagliptin over placebo was also demonstrated for the full treatment period,
with a treatment difference in HbA 1 c adjusted mean change from baseline to Week 52 of -
0.72% (95% CI -1.03, -0.41; p<0.0001). Statistically significant treatment differences
(p<0.0001) between the adjusted mean changes in HbAl c were observed across each visit
from baseline to Week 52. Thus, the reduction in HbA 1 c was sustained after 12 weeks, when
dose adjustment in background therapy was permitted. The difference between the 2
treatment groups in the adjusted mean change in FPG at Week 52 was not statistically
significant (1.34 mg/dL, p=0.8698). Of the patients with baseline HbAlc of at least 7.0%,
those in the linagliptin group were more likely to achieve an HbAlc below 7.0% after 52
weeks than patients in the placebo group (9.8% placebo; 18.2% linagliptin). Also, 6.1% of
linagliptin patients but none of the placebo patients with a baseline HbA1 c of at least 6.5%
attained an HbA 1 c below 6.5% after 52 weeks. Overall, a higher frequency of patients in the
linagliptin group had an HbAlc reduction of at least 0.5% (50.0% vs 32.3% in the placebo
group). There were no clinically relevant chan ges in mean body weight or waist
circumference from baseline to Week 52 for either treatment group.
More patients in the placebo group (51.8%) than in the linagliptin group (39.3%) had at least
one change in daily dose of background therapy between Weeks 12 and 52. The mean daily
dose increased by 8.48% in the placebo group, while it decreased by 13.81 % in the linagliptin
group.

Trial 1218.63:
A phase III double-blind, placebo-controlled, parallel group trial compared linagliptin 5 mg
once daily with placebo over 24 weeks in type 2 diabetic patients (age >70 years) with
insufficient glycaemic control (HbAic >7.0%) despite metformin and/or sulphonylurea and/or
insulin therapy. The primary endpoint was the change in HbAic from baseline after 24 weeks
of treatment. Background antidiabetic therapy with metformin was more common in the
placebo group (88.5%) than in the linagliptin group (83.1%), whereas sulphonylurea was
more common in the linagliptin group (58.8%) than in the placebo group (55.1%).

Results:
Superiority of linagliptin over placebo was demonstrated for the primary endpoint by a
treatment difference in HbAie adjusted mean change from baseline of -0.64% (95% CI: -0.81,
-0.48; p<0.0001) after 24 weeks. Sensitivity analyses confirmed the superiority of linagliptin.
The difference in treatment groups in adjusted mean change from baseline was -0.35% at
Week 6 and -0.57% at Week 12. The difference between the treatment groups in mean
changes in HbA lc was sustained beyond 12 weeks, when dose adjustment in background
therapy was allowed. Significantly more patients on linagliptin with baseline HbAlc >7.0%
achieved the target treatment outcome of HbAie <7.0% after 24 weeks of treatment (8.3%

REPONSE TO COMMENTS dated 23 June 2014