American Diabetes Association (ADA) 71st Scientific Sessions: Page 4 of 6

August 12, 2011

Linagliptin in Type 2 Diabetes Patients with Hyperglycemia

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 glycated hemoglobin A1c (HbA1c) levels compared with patients given placebo. 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 although many patients with type 2 diabetes who have poor glycemic control are treated with medications or receive education about the disease, a significant number of patients fail to meet their target levels.

Linagliptin is the first once-daily dipeptidyl peptidase-4 inhibitor that is excreted primarily through bile and the gut. Several previous studies have confirmed the drug’s safety and effectiveness when administered alone or added to treatment with metformin with or without a sulfonylurea.

For this meta-analysis, the authors included three trials that had enrolled a cumulative 2258 patients, but only considered data for the 396 patients with a baseline HbA1c level ≥9.0%. The trials had evaluated linagliptin as monotherapy or added to metformin or to a combination of metformin and a sulfonylurea.

Baseline characteristics for the 396 patients were similar between the groups. Approximately 41% of the patients were men, and the average age was around 56 years. Patients had a mean body mass index of approximately 29.0 kg/m2, and their mean HbA1c level was 9.4%. More than half the patients (57%) had received a diagnosis of type 2 diabetes >5 years earlier. On average, patients had been treated with at least 2 oral antidiabetic agents.

The 396 patients had been randomized to receive 5 mg of linagliptin (n = 287) or placebo (n = 101) daily, which was administered alone or combined with the other specified agents, for 24 weeks. At the time of the final analysis, data were missing for 7 patients in the linagliptin group and 1 in the placebo group. After 24 weeks of treatment, HbA1c levels decreased a mean of 1.2% for patients treated with linagliptin versus a mean decrease of 0.4% in those assigned to placebo (P <.0001).

These results were similar to the findings of each individual trial. The monotherapy trial showed an adjusted mean decrease in HbA1c levels of 0.9% for the linagliptin group versus an adjusted mean increase of 0.2% in the placebo arm (P = .0005).

In the metformin add-on trial, patients in the linagliptin group had an adjusted mean decrease of 1.0% in HbA1c levels compared with an adjusted mean decrease of 0.2% in the placebo cohort (P = .0062). In the metformin plus sulfonylurea add-on trial, HbA1c levels decreased an adjusted mean of 1.2% in the linagliptin arm compared with 0.4% in the placebo group (P <.0001).

The pooled analysis of all 396 patients showed 61.9% of patients taking linagliptin had an adverse event compared with 62.7% of patients given placebo. In the linagliptin group, 3.1% of patients had a serious adverse event compared with 4.9% of patients in the placebo arm. The incidence of hypoglycemia was 8.8% in the linagliptin group versus 4.9% in the placebo group.

The majority of hypoglycemia incidents in the linagliptin group (25 of 26) involved patients who were taking the drug with metformin and a sulfonylurea. The authors advised caution for patients using linagliptin with a sulfonylurea.

This study was supported by Boehringer Ingelheim.