Regardless of the degree of glycaemic control, linagliptin has lower hypoglycaemia risk than all doses of glimepiride, at all time points, over the course of a 2-year trial

Aim: To evaluate the risk of documented hypoglycaemia with glimepiride versus linagliptin. Methods: This was an exploratory analysis of data from a 2-year, randomized, double-blind study of the dipeptidyl peptidase-4 inhibitor linagliptin 5mg once daily (n=764) versus the sulphonylurea glimepiride 1-4 mg once daily (n= 755) in patients with type 2 diabetes uncontrolled by metformin. Patients randomized to glimepiride started on 1 mg and after 4 weeks were allowed to be individually uptitrated stepwise to glimepiride 4 mg if a fasting plasma glucose concentration <= 6.1 mmol/l was not achieved. Investigator-reported hypoglycaemia was evaluated by dose, over time, and by the degree of glycated haemoglobin (HbA1c) reduction. Results: The percentages of patients with at least one hypoglycaemic event at the individual maximum glimepiride dose were: 1mg, 45.0%; 2 mg, 50.8%; 3 mg, 36.1%; and 4mg, 27.7%. The incidence of hypoglycaemia was higher with glimepiride than with linagliptin (36.1 vs. 7.5%; p< 0.0001); after performing sensitivity analyses by excluding events during dose escalation (weeks 0-16), this difference remained significant (weeks 16-104: 25.8 vs. 5.9%; p< 0.0001). Notably, the incidence of hypoglycaemia was higher with glimepiride than with linagliptin in each quartile of HbA1c change from baseline (all p< 0.0001); the incidence of hypoglycaemic episodes was not increased with greater reductions in HbA1c in either group. In all 4-week intervals across the 2-year study, the incidence of hypoglycaemia was lower with linagliptin than with glimepiride. Conclusion: Linagliptin was associated with a lower risk of hypoglycaemia than glimepiride at all dose levels and time intervals, and regardless of change in HbA1c level.