Safety and tolerability of linagliptin in type 2 diabetes mellitus: a pooled analysis of 17 randomized controlled clinical trials

Abstract

Objective To evaluate the safety and tolerability of linagliptin as monotherapy, combined with metformin or combined with metformin and sulfonylurea in patients with type 2 diabetes mellitus (T2DM). Methods A total of 4 789 diabetes patients from 17 randomized clinical trials were included in this pooled analysis. Patients eligible for inclusion criteria with treatment naive or metformin monotherapy or metformin combined with sulfonylurea at baseline were selected. Individual data were collected and analyzed to evaluate the safety and tolerance of linagliptin.Subgroup analysis was carried out according to the classification of the original research program. Continuous variables were compared between groups using t-test or one-way analysis of variance. Results A total of 4 789 diabetes patients were included in this pooled-analysis, 3 343 patients in linagliptin group (including monotherapy, combined with metformin or combined with metformin+ sulfonylurea), and 1 446 patients in the placebo group. The incidence of adverse events was similar (52.4% vs 52.9%) in linagliptin vs placebo. The hypoglycemia event number in linagliptin was slightly higher than placebo (229 vs 59, OR=1.46, 95%CI 1.06-2.00). In patients with sulfonylureas as background treatment, the number of hypoglycemia event was slightly higher in Linagliptin group than that in placebo group (207 vs 49, OR=1.66, 95%CI 1.17-2.34), while in patients without sulfonylureas, hypoglycemia event was similar between the two groups (22 vs 10, OR=0.73, 95%CI 0.33-1.61). In addition, the risk of cardiovascular disease was similar between linagliptin and placebo (OR=1.19, 95%CI 0.88-1.62), and in sub-group analysis with ages, eGFR or body mass index (4.9% in the ligliptin group and 4.3% in the placebo group) as well. In addition, the number of adverse event confirmed by the clinical events committee was very low in both linagliptin and placebo (0.2% of patients in the ligliptin and placebo groups had cardiovascular death, myocardial infarction or stroke complex endpoints, and 0.3% of both group with cardiovascular death, myocardial infarction, stroke or unstable angina complex endpoints). Conclusion Based on this pooled analysis, linagliptin is a good treatment option for patients with type 2 diabetes with good safety and tolerance. Key words: Linagliptin; Diabetes mellitus, type 2; Safety; Tolerability