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cally meaningful treatment option for T2DM patients including those
whose treatment options are limited due to renal impairment.

As monotherapy and in combination with metformin and metformin
and a SU, linagliptin was proven to be most efficacious in patients with
higher baseline HbA values. In addition to significantly lowering HbA
1c
1c
(Table 6), linagliptin as monotherapy also had favourable effects on
FPG and 2h PPG. At 24 weeks these glycaemic parameters were re-
duced by -23 mg/dL (-1.3 mmol/L) and -58 mg/dL (-3.2 mmol/L), re-
spectively versus placebo. 113

As an add-on to metformin, linagliptin therapy significantly reduced
HbA at 24 weeks (Table 6), and also yielded significant, placebo-
1c
corrected reductions in mean FPG (-23 mg/dL, or -1.3 mmol/L) and 2h
PPG (- 67 mg/dl). Likewise, triple therapy (metformin + SU + linagliptin)
114
significantly reduced HbA (Table 6). The placebo-adjusted reduction
1c
in FPG with this triple therapy regimen was -13 mg/dL at 24 weeks. 115
In initial combination therapy with a pioglitazone, linagliptin therapy
significantly reduced HbA (Table 6). 116
1c
Table 6. Summary of linagliptin phase III clinical data

Monotherapy/ Total Duration Linagliptin dose Mean baseline Change in
Combination number of HbA HbA 1c
1c
patients (weeks) (%) (%)
Monotherapy 117 561 12 5 mg or 10 mg QD 8.01 -0.87 to -0.88
Monotherapy 118 503 24 5 mg QD -0.69
Metformin 119 701 24 5 mg QD 8.09 -0.49
Metformin and SU 120 1058 24 5 mg QD 7.0-10.0 -0.62
TZD 121 389 24 5 mg QD 7.5-11.0 -1.06
QD = once daily dosing

Safety and tolerability

The linagliptin studies conducted to date have demonstrated weight
neutrality in mono- and combination therapies. Additionally, there was
no increased risk of hypoglycaemia attributed to linagliptin use in mono-
therapy or combination therapy with metformin or pioglitazone. Like
the other DPP-4 inhibitors, the overall incidence rate of adverse events
reported for linagliptin was similar to placebo (55.0% versus 53.8%). Dis-
continuation of therapy due to adverse events was higher in patients
who received placebo as compared to linagliptin 5 mg (3.6 % versus
2.3 %). The most frequently reported adverse event in the linagliptin
clinical trial programme was hypoglycaemia because of those cases
observed in the triple combination study (metformin + sulphonylurea +
linagliptin). The incidence of hypoglycaemia in this study was 22.9% in
the treatment arm compared with 14.8% in the placebo arm. None of
these cases of hypoglycaemia was classified as severe.
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