Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes

P>Aims The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, linagliptin, added to ongoing metformin therapy, were assessed in patients with Type 2 diabetes who had inadequate glycaemic control (HbA(1c) >= 7.5 to < 10%; >= 58.5 to < 85.8 mmol/mol) with metformin alone. Methods Patients (n = 333) were randomized to receive double-blind linagliptin (1, 5 or 10 mg once daily) or placebo or open-label glimepiride (1-3 mg once daily). The primary outcome measure was the change from baseline in HbA(1c) at week 12 in patients receiving combination therapy compared with metformin alone. Results Twelve weeks of treatment resulted in a mean (sem) placebo-corrected lowering in HbA(1c) levels of 0.40% (+/- 0.14); 4.4 mmol/mol (+/- 1.5) for 1 mg linagliptin, 0.73% (+/- 0.14); 8.0 mmol/mol (+/- 1.5) for 5 mg, and 0.67% (+/- 0.14); 7.3 mmol/mol (+/- 1.5) for 10 mg. Differences between linagliptin and placebo were statistically significant for all doses (1 mg, P = 0.01; 5 mg and 10 mg, P < 0.0001). The change in mean (sem) placebo-corrected HbA(1c) from baseline was -0.90% (+/- 0.13); -9.8 mmol/mol (+/- 1.4) for glimepiride. Adjusted and placebo-corrected mean changes in fasting plasma glucose were -1.1 mmol/l for linagliptin 1 mg (P = 0.002), -1.9 mmol/l for 5 mg and -1.6 mmol/l for 10 mg (both P < 0.0001). One hundred and six (43.1%) patients reported adverse events; the incidence was similar across all five groups. There were no hypoglycaemic events for linagliptin or placebo, whereas three patients (5%) receiving glimepiride experienced hypoglycaemia. Conclusions The addition of linagliptin to ongoing metformin treatment in patients with Type 2 diabetes was well tolerated and resulted in significant and clinically relevant improvements in glycaemic control, with 5 mg linagliptin being the most effective dose.