Abstract
IntroductionEmpagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, ameliorates hyperglycemia in patients with type 2 diabetes (T2D) by inducing sustained glucosuria. Empagliflozin treatment was previously associated with a transient increase in 24-h urine volume in Caucasian patients with T2D, however comparable evidence in Japanese T2D individuals is scarce. We therefore assessed acute and chronic changes in 24-h urine volume and fluid intake with empagliflozin in Japanese patients with T2D.MethodsIn this randomized, double-blind, placebo-controlled, parallel-group, multiple-dose, 4-week trial, 100 Japanese patients with T2D were randomized to receive either 1, 5, 10, or 25 mg empagliflozin or placebo once-daily. Changes from baseline in 24-h urine volume and fluid intake were assessed at days 1, 27, and 28 after the initiation of empagliflozin.ResultsThe 24-h urine volume and fluid intake were comparable across all treatment groups at baseline. Patients treated with either 10 or 25 mg empagliflozin (i.e., the licensed doses in Japan) showed a significant increase in 24-h urine volume compared to placebo at day 1 (mean change from baseline: + 0.83, + 1.08, and + 0.29 L/day in the empagliflozin 10 and 25 mg groups and the placebo group, respectively; both p < 0.001 vs. placebo). However, 24-h urine volume levels in the empagliflozin groups were comparable to placebo at day 27 and 28 (differences vs placebo < 0.1 L/day; p > 0.05). The 24-h fluid intake was comparable across all study groups throughout the entire study period. No events consistent with dehydration were reported during empagliflozin treatment.ConclusionTreatment initiation with empagliflozin in Japanese patients with T2D was associated with transient diuresis; however, overall urine volume returned towards baseline levels within 4 weeks of treatment. These findings are consistent with a physiological, adaptive mechanism of the kidney to maintain overall body fluid balance in response to treatment initiation with a SGLT2 inhibitor.Trial Registration NumberNCT00885118.FundingNippon Boehringer Ingelheim Co., Ltd.
Highlights
Empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, ameliorates hyperglycemia in patients with type 2 diabetes (T2D) by inducing sustained glucosuria
We previously reported that 24-h urinary glucose excretion (UGE) was significantly increased on day 1 with either empagliflozin 10 or 25 mg, and a significant increase in 24-h UGE was maintained throughout the active treatment period until day 28 (Fig. 2a) [8]
On day 1, 24-h urine volume increased significantly in patients treated with the 10 mg and 25 mg doses of empagliflozin compared to placebo (Fig. 2b)
Summary
Empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, ameliorates hyperglycemia in patients with type 2 diabetes (T2D) by inducing sustained glucosuria. SGLT2 inhibitors are a new class of oral antidiabetic drugs (OADs) that target glucose reabsorption in the kidney, thereby facilitating glucose excretion into urine. This removal of excess glucose from the body is associated with a reduction in blood glucose levels in patients with type 2 diabetes (T2D) [1]. In previous phase 2–3 clinical trials, treatment with once-daily empagliflozin significantly ameliorated hyperglycemia, irrespective of commonly used glucose-lowering background therapy, and was well tolerated overall in T2D patients, including those of Japanese ethnicity [7,8,9,10]
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