Efficacy and safety of linagliptin in persons with Type-2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study1

Aims To examine the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in persons with Type 2 diabetes mellitus inadequately controlled [HbA1c 53–86 mmol/mol (7.0–10.0%)] by metformin and sulphonylurea combination treatment. Methods A multi-centre, 24-week, randomized, double-blind, parallel-group study in 1058 patients comparing linagliptin (5 mg once daily) and placebo when added to metformin plus sulphonylurea. The primary endpoint was the change in HbA1c after 24 weeks. Results At week 24, the linagliptin placebo-corrected HbA1c adjusted mean change from baseline was −7 mmol/mol (−0.62%) [95% CI −8 to −6 mmol/mol (−0.73 to −0.50%); P < 0.0001]. More participants with baseline HbA1c≥ 53 mmol/mol (≥ 7.0%) achieved an HbA1c < 53 mmol/mol (< 7.0%) with linagliptin compared with placebo (29.2% vs. 8.1%, P < 0.0001). Fasting plasma glucose was reduced with linagliptin relative to placebo (−0.7 mmol/l, 95% CI −1.0 to −0.4; P < 0.0001). Improvements in homeostasis model assessment of β-cell function were seen with linagliptin (P < 0.001). The proportion of patients who reported a severe adverse event was low in both groups (linagliptin 2.4%; placebo 1.5%). Symptomatic hypoglycaemia occurred in 16.7 and 10.3% of the linagliptin and placebo groups, respectively. Hypoglycaemia was generally mild or moderate; severe hypoglycaemia was reported in 2.7 and 4.8% of the participants experiencing hypoglycaemic episodes in the linagliptin and placebo groups, respectively. No significant weight changes were noted. Conclusions In patients with Type 2 diabetes, adding linagliptin to metformin given in combination with a sulphonylurea significantly improved glycaemic control and this was well tolerated. Linagliptin could provide a valuable treatment option for individuals with inadequate glycaemic control despite ongoing combination therapy with metformin and a sulphonylurea