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.