Glucose-lowering effects of 7-day treatment with SGLT2 inhibitor confirmed by intermittently scanned continuous glucose monitoring in outpatients with type 1 diabetes. A pilot study

Abstract

The present study used intermittently scanned continuous glucose monitoring (isCGM) in 10 patients with type 1 diabetes mellitus (T1DM) to evaluate the efficacy and safety of 7-day outpatient treatment with the combination of intensive insulin therapy and sodium-glucose transporter 2 inhibitor (SGLT2-I). All participants wore isCGM and were treated with either 50 mg/day ipragliflozin or 5 mg/day dapagliflozin. The primary outcome, percent time with glucose at 70-180 mg/dL (TIR: time in range), improved significantly following the addition of SGLT2-I (p = 0.005). TIR increased from 36.0% before addition of SGLT2-I to 70.7% on day 7. Although none of the patients achieved TIR of 70% or higher before the addition of SGLT2-I, 6 patients met that criteria TIR on day 7. The secondary outcome measures, standard deviation (SD) of glucose, average plasma glucose, percent time with glucose at >180 mg/dL (TAR: time above range), maximum plasma glucose, high blood glucose index (HBGI) and average nocturnal plasma glucose (midnight to 05:59 AM) detected by isCGM, also improved significantly by SGLT2-I. There were no significant differences in percent time with glucose at <70 mg/dL (TBR: time below range), minimum plasma glucose and low blood glucose index (LBGI). Our results using isCGM in an actual clinical setting showed that 7-day use of SGLT2-I with intensive insulin therapy improved plasma glucose fluctuations and mean plasma glucose levels without inducing hypoglycemia in patients with T1DM.

Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study

“…Regarding the secondary endpoints, we showed that the ipragliflozin treatment significantly decreased the participants' required insulin dose and significantly improved their glycaemic control (decrease in HbA1c and increase in TIR) and their glycaemic variability (decreases in SD, CV% and MAGE) without increasing TBR, as reported in several studies 7,9,11–13 …”

“…Regarding the secondary endpoints, we showed that the ipragliflozin treatment significantly decreased the participants' required insulin dose and significantly improved their glycaemic control (decrease in HbA1c and increase in TIR) and their glycaemic variability (decreases in SD, CV% and MAGE) without increasing TBR, as reported in several studies. 7,9,[11][12][13] The association between increased glucagon and glycaemic stabilization in persons with T1D who are treated with SGLT2 inhibitors is not fully understood. In a recent study, dapagliflozin treatment did not significantly increase the counter-regulatory glucagon response to a hypoglycaemic clamp protocol, but it increased fasting glucagon levels when normoglycaemia was present in subjects with T1D.…”

“…9 Several studies of Japanese adults with T1D treated with SGLT2 inhibitors have also shown positive outcomes in CGM measurements. [10][11][12][13] However, the above-cited meta-analysis revealed an increased risk of diabetic ketoacidosis (DKA) as a side effect of SGLT2 inhibitors in T1D. 7 Because of concerns about DKA, the use of SGLT2 inhibitors for T1D is not approved by the US Food and Drug Administration.…”

“…A pooled analysis of CGM data from the DEPICT‐1 4 and DEPICT‐2 8 phase III clinical trials of dapagliflozin showed a significant reduction in glycaemic variability 9 . Several studies of Japanese adults with T1D treated with SGLT2 inhibitors have also shown positive outcomes in CGM measurements 10–13 …”