Linagliptin appears safe, effective for long-term use, study indicates

Long-term use of linagliptin appears to be safe and effective, according to a study funded by the drug's manufacturer.

Researchers performed a 78-week open-label extension study plus one week of follow-up in patients with type 2 diabetes who had participated in one of four 24-week randomized, double-blind, placebo-controlled parent trials. Patients were drawn from 231 sites in 32 countries. Regimens studied in the parent trials included once-daily oral linagliptin alone or in combination with metformin, metformin plus a sulfonylurea, or pioglitazone. The 1,532 patients who received one of these regimens during a parent trial continued to receive it for up to 102 weeks, while the 589 patients who had received placebo during the parent trials were switched to linagliptin.

The goal of the study was to examine the safety, efficacy and tolerability of linagliptin alone or in combination with other oral glucose-lowering agents over the long term. The safety and tolerability outcomes included incidence and intensity of adverse events, withdrawal because of adverse events, and physical exam and other test results, as well as hypoglycemic events. Secondary efficacy outcomes included change in hemoglobin A1c (HbA1c), HbA1c below 7.0% at week 78, and an HbA1c reduction of at least 0.5% by week 78. Change over time in fasting plasma glucose, body weight and use of rescue therapy were also assessed. The study, which was funded by Boehringer Ingelheim, appeared in the August International Journal of Clinical Practice.

The study cohort had a mean age of 57.5 years; approximately three-quarters were younger than age 65, and slightly more than half were men. Patients who had been assigned to an active treatment group in their parent study retained their previously achieved reductions in HbA1c during the 78-week extension, with a change of −0.8% from baseline to week 102. Eighty-one percent of patients reported at least one adverse event during the 78-week extension, with the highest incidence in the metformin plus sulfonylurea group. Drug-related adverse events occurred in 14.3% of patients, and 13.9% of patients developed hypoglycemia (13.6% of those who had previously received active treatment and 14.6% of those who had switched to linagliptin from placebo). Body weight showed no clinically relevant changes over the study period.

The authors acknowledged that the open-label nature of the 78-week extension period and lack of blinded comparison limit interpretation of their safety data. However, they concluded that linagliptin provided sustained, long-term glycemic control, either alone or combined with other oral therapy for type 2 diabetes, without notable changes in its safety profile.