Efficacy and safety of linagliptin in subjects with type 2 diabetes mellitus and poor glycemic control: Pooled analysis of data from three placebo-controlled phase III trials.

AIMS: To evaluate the efficacy/safety of dipeptidyl peptidase-4 inhibitor, linagliptin, in subjects with insufficiently controlled type 2 diabetes mellitus (T2DM), and factors influencing treatment response.

METHODS: Pooled analysis of data from 2258 subjects in three 24-week phase III, randomized, placebo-controlled, parallel-group studies, who received oral linagliptin (5 mg/day) or placebo as monotherapy, added-on to metformin, or added-on to metformin plus sulfonylurea was performed.

RESULTS: Among 388 subjects with HbA1c ≥9.0%, adjusted mean baseline HbA1c (9.4% both groups) declined to 8.3% in linagliptin group and 9.1% in placebo group at 24 weeks (P<.0001) and adjusted mean change from baseline was 1.2% (vs. 0.4%, placebo). Linagliptin significantly lowered fasting plasma glucose levels vs. placebo (1.6 mmol/l vs. 0.4 mmol/l); treatment difference, 1.1 mmol/l (95% CI, -1.7 to -0.5). Treatment and washout of previous oral antidiabetes drugs were the only factors to independently affect HbA1c change at week 24. Adverse event rates were similar for linagliptin (61.9%) and placebo (62.7%). Hypoglycemia was rare with linagliptin monotherapy/add-on to metformin (≤1%) and increased when linagliptin was added to metformin plus sulfonylurea (linagliptin, 17.9% vs. placebo, 8.3%).

CONCLUSIONS: Linagliptin was an effective, well-tolerated treatment in subjects with T2DM and insufficient glycemic control, both as monotherapy or added-on to metformin/metformin plus sulfonylurea.