Linagliptin to Treat Type 2 Diabetes Patients with Severe Renal Impairment

San Diego—In a randomized, double-blind, placebo-controlled, phase 3 trial of patients with type 2 diabetes and severe renal impairment, researchers found that those who took linagliptin for 12 weeks had a significant reduction in hemoglobin A1c (HbA1c) level compared with a control group. The therapy did not lead to unacceptable side effects and did not affect renal parameters or blood potassium levels. The results were presented at the ADA meeting in a poster titled Safety and Efficacy of Linagliptin in Type 2 Diabetes Patients with Severe Renal Impairment. The authors noted that patients with type 2 diabetes often suffer from declining renal function, and treatment options are limited. For instance, patients should not take many oral antidiabetic drugs (including metformin) because they have safety and tolerability issues and side effects such as fluid retention and hypoglycemia. In May, linagliptin became the first once-daily dipeptidyl peptidase-4 inhibitor approved by the US Food and Drug Administration that is excreted mostly through the bile and gut and does not need to be adjusted in patients with declining renal function. Patients were included in the trial if they had a baseline HbA1c level between 7.0% and 10.0% and severe renal impairment, defined as glomerular filtration rate (GFR) <30 mL/min/1.73 m2. They were randomized to receive daily 5-mg doses of linagliptin (n=68) or placebo (n=65) for 12 weeks, although 2 patients in the linagliptin group and 3 patients in the placebo group did not complete the 12 weeks. The baseline characteristics were well balanced. The mean age was 64.4 years, the mean HbA1c level was 8.2%, and the mean GFR was 23.5 mL/min/1.73 m2. In addition, 96% of patients had diabetes for >5 years. After 12 weeks of treatment, the mean HbA1c level had declined 0.76% in the linagliptin group compared with a drop of 0.18% in the placebo group (P=.0001). For patients with a baseline HbA1c level ≥9.0%, the mean HbA1c level dropped by a mean of 1.46% in those taking linagliptin compared with 0.28% in those in the placebo group (P=.0021). The rate of adverse events (AEs) and serious AEs was higher in the linagliptin group: 85.3% of patients taking linagliptin had an AE and 13.2% had a serious AE compared with 70.8% and 4.6%, respectively, in patients receiving placebo. Meanwhile, 51.5% of patients in the linagliptin group had hypoglycemia compared with 27.7% in the placebo group. The authors mentioned most of the hypoglycemia cases were asymptomatic or of mild intensity and hypothesized that the higher rates in the linagliptin group may have occurred because patients did not change their antidiabetic, glucose-lowering background therapy during the study. This study was supported by Boehringer Ingelheim.