Abstract

IntroductionThe efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM).MethodsThe subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean glucose concentrations, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC) (≥180, <70 mg h/dL) after the start of administration were compared with the pretreatment values. In addition, we compared changes in the number of insulin units between basal and bolus insulin. Furthermore, we investigated the influence of canagliflozin on oxidative stress markers and cytokines using 8-hydroxy-2′-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and adiponectin as parameters.ResultsThe mean glucose concentrations decreased from 161.1 to 139.1 mg/dL (P < 0.01). The SD decreased from 36.5 to 29.6 mg/dL (P = 0.05). The MAGE decreased from 89.2 to 77.4 mg/dL (P < 0.01), and the MODD decreased from 34.3 to 25.5 mg/dL (P < 0.05). All parameters showed significant improvements in diurnal changes. AUC of ≥180, i.e., the total area of blood glucose levels at or above 180 on the blood glucose curve of CGM, decreased from 339.1 to 113.6 mg/dL (P < 0.05). AUC of <70, i.e., the total area of blood glucose levels below 70 on the blood glucose curve of CGM, slightly decreased from 1.6 to 0.3 mg/dL (P = 0.08). The total number of basal insulin units decreased from 128 to 76, and that of bolus insulin decreased from 266 to 154; the dose of insulin could be markedly decreased. In addition, the mean 8-OHdG level decreased from 11.4 to 10.8 ng/mg Cre (P < 0.05), and the mean TNF-α level decreased from 2.31 to 1.79 pg/mL (P = 0.10). The mean adiponectin level increased from 5.01 to 5.53 μg/mL (P < 0.05).ConclusionCanagliflozin improved blood glucose changes in type 2 diabetes using insulin. In addition, the results suggest its antioxidant actions.Trial RegistrationUniversity Hospital Medical Information Network (UMIN no. 000019429).

Highlights

  • The efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established

  • We investigated the influence of canagliflozin on oxidative stress markers and cytokines using 8-hydroxy-20-deoxyguanosine (8-OHdG), tumor necrosis factor-a (TNF-a), and adiponectin as parameters

  • The action mechanism of sodium–glucose cotransporter 2 (SGLT2) inhibitors differs from insulin secretion, and they may exhibit blood glucose-lowering effects even in patients with unfavorable blood glucose control during insulin therapy

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Summary

Introduction

The efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established. We examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM). The action mechanism of sodium–glucose cotransporter 2 (SGLT2) inhibitors differs from insulin secretion, and they may exhibit blood glucose-lowering effects even in patients with unfavorable blood glucose control during insulin therapy. Few studies have examined the additional effects of SGLT2 inhibitors during insulin therapy [1,2,3]. The additional administration of SGLT2 inhibitors may potentiate treatment with hypoglycemia avoidance, making it possible to decrease the dose of insulin. We examined whether the additional administration of SGLT2 inhibitors during insulin therapy improves blood glucose dynamics without increasing the body weight or incidence of hypoglycemia using CGM. We investigated the influence of SGLT2 inhibitors on oxidative stress markers and cytokines

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