Effect of linagliptin monotherapy on glycaemic control and markers of β ‐cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial

Abstract

Aim: To assess the safety and efficacy of the potent and selective dipeptidyl peptidase‐4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment‐naive or who had received one oral antidiabetes drug (OAD). Methods: This multicentre, randomized, parallel group, phase III study compared linagliptin treatment (5 mg once daily, n = 336) with placebo (n = 167) for 24 weeks in type 2 diabetes patients. Before randomization, patients pretreated with one OAD underwent a washout period of 6 weeks, which included a placebo run‐in period during the last 2 weeks. Patients previously untreated with an OAD underwent a 2‐week placebo run‐in period. The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment. Results: Linagliptin treatment resulted in a placebo‐corrected change in HbA1c from baseline of −0.69% (p < 0.0001) at 24 weeks. In patients with baseline HbA1c ≥ 9.0%, the adjusted reduction in HbA1c was 1.01% (p < 0.0001). Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5% at 24 weeks than those in the placebo arm (47.1 and 19.0%, respectively; odds ratio, OR = 4.2, p < 0.0001). Fasting plasma glucose improved by −1.3 mmol/l (p < 0.0001) with linagliptin vs. placebo, and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2‐h postprandial glucose of −3.2 mmol/l (p < 0.0001). Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025), Homeostasis Model Assessment‐%B (p = 0.049) and disposition index (p = 0.0005). There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third‐party intervention. Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin. Conclusions: Monotherapy with linagliptin produced a significant, clinically meaningful and sustained improvement in glycaemic control, accompanied by enhanced parameters of β ‐cell function. The safety profile of linagliptin was comparable with that of placebo.