Forst_2010_Diabet.Med_27_1409

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.