Linagliptin in Type 2 Diabetes Patients with Hyperglycemia

San Diego—A pooled analysis of three phase 3, placebo-controlled, randomized trials found that patients with type 2 diabetes and poor glycemic control who took linagliptin for 24 weeks had a statistically significant reduction in hemoglobin A1c (HbA1c) level compared with a placebo group. In addition, the rate of adverse events was nearly identical between the groups. Results were presented at the ADA meeting in a poster titled Efficacy and Safety of Linagliptin in People with Type 2 Diabetes and Poor Glycemic Control. The authors said that many patients with type 2 diabetes who have poor glycemic control are treated with medications or receive education about the disease, although a significant number of patients do not meet their target goals. Linagliptin is the first once-daily dipeptidyl peptidase-4 inhibitor that is primarily excreted through bile and the gut. Several previous studies confirmed the drug’s safety and effectiveness as a monotherapy and as an add-on treatment to metformin and metformin plus a sulfonylurea. In this trial, the authors performed an analysis of 3 of the trials that enrolled 2258 patients, but they only included the 396 patients with an HbA1c level ≥9.0%. The trials had evaluated linagliptin’s use as a monotherapy and as an add-on treatment to metformin and metformin plus a sulfonylurea. The 396 patients were randomized to receive 5 mg of linagliptin daily for 24 weeks (n=287) or placebo daily for 24 weeks (n=101). At the time of the analysis, data were missing for 7 patients in the linagliptin group and 1 in the placebo group. Baseline characteristics were similar between the groups. The mean age was approximately 56 years, the mean body mass index was approximately 29.0 kg/m2, and the mean HbA1c level was 9.4%. Approximately 41% of the patients were male, and approximately 57% had had type 2 diabetes for a mean of >5 years and been treated with a mean of ≥2 oral antidiabetic agents. After 24 weeks of treatment, patients in the linagliptin group had an adjusted mean decrease of 1.2% in their HbA1c level compared with an adjusted mean decrease of 0.4% in the placebo group (P<.0001). The individual trials showed similar results. In the monotherapy trial, patients in the linagliptin group had an adjusted mean decrease of 0.9% in their HbA1c level compared with an adjusted mean increase of 0.2% in the placebo group (P=.0005). Meanwhile, in the metformin add-on trial, patients in the linagliptin group had an adjusted mean decrease of 1.0% in their HbA1c level compared with an adjusted mean decrease of 0.2% in the placebo group (P=.0062). In the metformin plus sulfonylurea add-on trial, patients who took linagliptin had an adjusted mean decrease of 1.2% in their HbA1c level compared with an adjusted mean decrease of 0.4% in the placebo group (P<.0001). The pooled analysis of the 396 patients found that 61.9% of those taking linagliptin had an adverse event and 3.1% had a serious adverse event compared with 62.7% and 4.9%, respectively, of patients taking placebo. The authors reported that 8.8% of patients in the linagliptin group had hypoglycemia compared with 4.9% of patients in the placebo group. However, 25 of the 26 cases of hypoglycemia in the linagliptin group occurred in patients taking add-on metformin and a sulfonylurea. Thus, the authors advised caution when taking a sulfonylurea and said the dosage could be reduced when appropriate. This study was supported by Boehringer Ingelheim.