Efficacy and safety of linagliptin in type 2 diabetes with comorbid hypertension and microalbuminuria

Abstract

Objective To investigate the efficacy and safety of linagliptin, one dipeptidyl peptidase Ⅳ (DPP-4) inhibitor, in type 2 diabetes mellitus (T2DM) patients with hypertension and microalbuminuria. Methods In eight completed (before October 2015) phase Ⅲ clinical trials which were designed to evaluate the efficacy of linagliptin (alone or combined with other oral antidiabetic drugs), all the T2DM patients with hypertension and microalbuminuria at baseline were included in this pooled analysis. The included patients could be drug-naive, with metformin monotherapy or metformin combined with sulfonylureas dual therapy at baseline. In each clinical trial, participants were randomized to receiving linagliptin 5mg daily or placebo for 24weeks. Efficacy was assessed by the change from baseline in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) after 24 weeks of treatment. Safety endpoint was evaluated by frequency of adverse events. Efficacy endpoints were analyzed with the analysis of covariance. Safety data were analyzed using descriptive statistics. Results A total of 532 T2DM patients were included (placebo group 152, linagliptin group 380). At baseline the mean age was 60 years, mean HbA1c was 8.2% and mean FPG was 169 mg/dl (1 mg/dl=0.056 mmol/L) . After 24 weeks of treatment, placebo-corrected mean change in HbA1c and FPG were-0.57%(95% CI:-0.74%--0.39%, P<0.000 1) and-24 mg/dl [95%CI: (15~32) mg/dl, P<0.000 1], respectively. The incidence of any adverse events (both for 63.2%) was the same between placebo group and linagliptin group. Also, the changes of blood pressure and serum lipid concentration were similar between the two groups. Conclusion Linagliptin may significantly improve glycemic control and be well tolerated in T2DM patients with hypertension and microalbuminuria. Key words: Diabetes mellitus, type 2; Hypertension; Microalbuminuria; Linagliptin