Combination treatment with empagliflozin 10 or 25 mg and linagliptin 5 mg was well-tolerated and led to significantly better clinical outcomes for individuals with type 2 diabetes compared with linagliptin 5 mg combined with placebo, according to a study published in Diabetes, Obesity and Metabolism.
Study participants in this placebo-controlled, double-dummy, double-blind, phase 3, randomized, 52-week, multicenter trial were men and women ≥20 years of age, and participation took place at 40 Japanese study sites from May 2015 to March 2017. To ensure that all individuals had been pretreated with linagliptin without showing adequate glycemic control, those who were not already being treated with linagliptin for ≥16 weeks entered an open-label stabilization period of 5 mg linagliptin treatment for 16 weeks before baseline. Of the participants screened, 106 discontinued before randomization because their glycated hemoglobin (HbA1c) levels were within healthy range.
All 275 study participants were randomly assigned 2:1 into groups treated with either empagliflozin 10 mg combined with linagliptin 5 mg (n=182) or linagliptin 5mg combined with placebo (n=93) from baseline to 24 weeks. At this point, the participants with HbA1c levels at ≥7.0% were up-titrated to empagliflozin 25 mg (n=126) or matching placebo (n=80) for 24 weeks starting at week 28. Participants with healthy HbA1c levels continued the initial treatment for the full 52 weeks.
Discontinuations due to adverse events were equal in both empagliflozin and placebo groups, with more participants experiencing adverse events in the linagliptin monotherapy group. Nine serious adverse events were reported by 8 participants in the empagliflozin/linagliptin group, and 3 were assessed by investigators as drug-related, although the 1 fatality (cerebral hemorrhage) could not be confirmed by the cardiovascular adjudication committee because the participant died at home and there was no autopsy.
Investigators conclude that “switching from linagliptin monotherapy to empagliflozin/linagliptin [fixed-dose combination] was well tolerated and resulted in clinically significant reductions in HbA1c, [fasting plasma glucose], body weight, and [systolic blood pressure] in Japanese patients with [type 2 diabetes]. Thus, empagliflozin/linagliptin fixed-dose combination represents an attractive therapeutic option for these patients, with potentially additive cardio-renal benefits from empagliflozin and a formulation expected to improve adherence.”
This study was funded by Boehringer Ingelheim and Eli Lilly and Company.
Kawamori R, Haneda M, Suzaki K, et al. Empagliflozin as add‐on to linagliptin in a fixed‐dose combination in Japanese patients with type 2 diabetes: glycaemic efficacy and safety profile in a 52‐week, randomized, placebo‐controlled trial [published online May 15, 2018]. Diabetes Obes Metab. doi: 10.1111/dom.13352