Clinical Benefit of Switching from Low-Dose to High-Dose Empagliflozin in Patients with Type 2 Diabetes

Abstract

Introduction: Sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors ameliorate blood glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting the reabsorption of glucose from the kidneys, thus increasing urinary glucose excretion. Most SGLT2 inhibitors have been reported to exert dose-dependent effects. However, little is known about the benefits of increasing the dose of SGLT2 inhibitors in clinical use. The aim of the present study was to investigate the effect of increasing the dose of the SGLT2 inhibitor empagliflozin in T2DM. Methods: We collected 52 subjects with T2DM with inadequate glycemic control. The dose of empagliflozin was increased from 10 to 25 mg, taken once daily, and the alterations in glycemic control and several other clinical parameters were evaluated.

A Comparative Study on the Efficacy and Safety of Dose Escalation of Luseogliflozin in Type 2 Diabetes Mellitus Patients With Poor Glycemic Control

“…In addition, Matsumura et al reported that baseline DBP and TG were independent predictors of HbA1c decrement [6]. In the present study, DBP was also significantly higher in the dose-escalation group at baseline, and differences in patient backgrounds may have contributed to the decrease in HbA1c in the doseescalation group.…”

“…A meta-analysis of 51 randomized clinical trials involving 23,989 patients with T2DM has reported that empagliflozin, dapagliflozin, and canagliflozin significantly decreased regulated glycemia, BW, BP, and HDL in a dose-dependent manner [5]. A retrospective study involving empagliflozin administration six months after dose escalation showed significant decrements in BW, BMI, γ-GTP, TG, FPG, and HbA1c in type 2 diabetic patients [6].…”

“…SGLT2 inhibitors that can be prescribed in higher doses in Japan include luseogliflozin, empagliflozin, dapagliflozin, and ipragliflozin. While the overall benefit of canagliflozin, dapagliflozin, and empagliflozin was found to be dose-dependent in a metaanalysis [5], and a retrospective study of empagliflozin showed an increase in dose [6], another metaanalysis [7] has reported that higher doses were as effective as regular doses; hence, it remains unclear whether the effects of SGLT2 inhibitors are dose-dependent. Among SGLT2 inhibitors, luseogliflozin (LUSEO) is a drug used at a minimum dose of 2.5 mg/day, which can be increased to 5 mg/day.…”

Effectiveness and Tolerability of the Intensification of Canagliflozin Dose from 100 mg to 300 mg Daily in Patients with Type 2 Diabetes in Real Life: The INTENSIFY Study

“…In the observational REAL-WECAN study published by our group, patients who intensified their antihyperglycemic therapy by switching to CANA300 from other SGLT-2is (also including CANA100) showed similar results to those observed in the present study [ 15 ]. However, in a recent RWS evaluating the intensification of another SGLT-2i, empagliflozin, from 10 mg to 25 mg, the HbA1c and weight reductions at 24 weeks were only −0.13% and −0.6 kg, respectively [ 21 ]. Both RCTs and RWS suggest greater effectiveness of CANA300 within the SGLT-2i class, and intensification to the higher dose of canagliflozin could delay the need to add new drugs and therefore avoid an increase in treatment burden.…”