A multicenter, randomized, double-blind, placebo-controlled, parallel-group study found that combining linagliptin treatment with a sulfonylurea (SU) in diabetic patients was well tolerated and produced statistically significant and clinically relevant A1c reductions….
There were comparable safety results between placebo and linagliptin, an oral dipeptidyl peptidase-4 inhibitor under development to treat Type 2 diabetes.
Furthermore, adding linagliptin did not lead to a significant increase in hypoglycemia. The results indicated that linagliptin could be used as an alternative to uptitrating SU for patients who are failing therapy with only SU or in combination.
The 18-week study aimed to determine the efficacy, safety, and tolerability of linagliptin administered with SU background therapy in participants with T2DM and insufficient glycemic control. The patients underwent placebo treatment for 2 weeks before being randomized into 2 groups: 84 continued to take the placebo; 161 took 5 mg of linagliptin per day.
At the beginning of a 4-week washout period, the researchers withdrew any oral antidiabetic (OAD) agent other than SU. Throughout the trial, the researchers administered SU in the same dosage. The researchers evaluated the primary end point (change in HbA1c from baseline after 18 weeks of treatment) by utilizing an analysis of covariance adjusted for treatment, prior OADs, and baseline HbA1c.
The mean baseline characteristics were similar for both groups: HbA1c 8.6%; fasting plasma glucose (FPG) 179.6 mg/dL; age 56.9 years; body mass index 28.3 kg/m2. At week 18, the adjusted mean change in HbA1c from baseline was –0.47%, indicating the effectiveness of linagliptin over placebo (P<.0001). The statistically significant differences between linagliptin and placebo for HbA1c were sustained at weeks 6, 12, and 18 (P<.0001 in each case).
If participants had a baseline HbA1c ≥7.0%, they were 6 times more likely to achieve a response of HbA1c to ≤7.0% after 18 weeks when treated with linagliptin (15.2%) rather than placebo (3.7%) (odds ratio [OR], 6.47; P=.006). In addition, at 18 weeks, participants treated with linagliptin were more likely to achieve a reduction in HbA1c ≥0.5% than those who received placebo (OR, 5.12; P<.0001). By the study's end, participants taking linagliptin showed improvements in glycemic control, which was reflected in the difference in adjusted mean change in FPG from baseline of –6.4 mg/dL (P=.24).
Patients in the placebo group (15.9%) were more than twice as likely to require rescue therapy as those who received linagliptin (7.6%), although the frequency of adverse events (AEs) was similar: 42.2% in the linagliptin group and 42.9% in the placebo group. The investigator considered 13 of the 161 AEs (8.1%) in the linagliptin group and 8 of the 84 AEs (9.5%) in the placebo group as drug-related. However, none of the severe AEs were considered drug-related.
Presented at EASD 2010