Long‐term (52‐week) efficacy and safety of dapagliflozin as an adjunct to insulin therapy in Japanese patients with type 1 diabetes: Subgroup analysis of the DEPICT‐2 study

Abstract

Aim: To examine the long-term efficacy and safety of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor used to treat type 1 diabetes, in the Japanese subpopulation of the DEPICT-2 study.Materials and Methods: Patients with type 1 diabetes were randomized to dapagliflozin 5 mg (n = 55), dapagliflozin 10 mg (n = 41) or placebo (n = 58) plus insulin for a 24-week, double-blind period followed by a 28-week, single-blind extension phase.Results: From baseline to 24 weeks, dapagliflozin reduced HbA1c compared with placebo (mean change of −0.58% and −0.80% for 5 and 10 mg, respectively), and an HbA1c reduction was observed up to 52 weeks. Compared with placebo, dapagliflozin 5 and 10 mg increased the proportion of patients achieving HbA1c reductions of 0.5% or more without severe hypoglycaemia events and reduced glycaemic variability assessed via continuous glucose monitoring. Both dapagliflozin doses decreased body weight and total daily insulin dose at 24 weeks compared with placebo; these reductions were maintained up to 52 weeks. Diabetic ketoacidosis occurred in both dapagliflozin groups (one and two cases, respectively) but not with placebo.Conclusions: Efficacy and safety results from the Japanese subpopulation of the DEPICT-2 study were generally consistent with those from the overall population, indicating that long-term dapagliflozin adjunct to insulin therapy improves glycaemic control without an increased risk of hypoglycaemia but with a risk of diabetic ketoacidosis in Japanese patients with type 1 diabetes.

Therapeutic effect and rebound evaluation of dapagliflozin on glycated hemoglobin (HbA1c) in type 1 diabetes mellitus patients

“…Moreover, Melin et al (2022 ) found that dapagliflozin pharmacokinetics was similar in adults with T1DM and T2DM. In addition, it was interesting to note that more and more research results suggested that dapagliflozin was a promising adjunct treatment to insulin which improves glycemic control in patients with inadequately controlled T1DM ( Dandona et al, 2017 ; Mathieu et al, 2018 ; Parkinson et al, 2019 ; Araki et al, 2020 ; Araki et al, 2021 ; Biester et al, 2021 ). Wang et al (2022 ) explored the quantitative relationship between dapagliflozin and loss of weight in T1DM patients and found that to achieve the plateau period in the loss of weight, 5 mg/day dapagliflozin was required for at least 41.6 weeks.…”

“…The mechanism of dapagliflozin is to promote glycemic disposal in an insulin-independent way, thereby decreasing postprandial glycemia and glycemic excursions accompanied by an inferior insulin demand without increasing the risk of hypoglycemia ( Li et al, 2022 ). It is interesting to note that research results suggest that dapagliflozin is a promising adjunct treatment to insulin which improves glycemic control in patients with inadequately controlled T1DM ( Dandona et al, 2017 ; Mathieu et al, 2018 ; Parkinson et al, 2019 ; Araki et al, 2020 ; Araki et al, 2021 ; Biester et al, 2021 ); meanwhile, it significantly decreases the glycated hemoglobin (HbA1c) ( Li et al, 2022 ). HbA1c identifies average plasma glucose concentration, and for people with diabetes this is important as the higher the HbA1c, the greater the risk of developing diabetes-related complications ( Rydberg et al, 2022 ; Wikstrom et al, 2022 ).…”

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Urine Albumin to Creatinine Ratio in Type 2 Diabetes Mellitus Patients and Medication Care

“…SGLT-2 inhibitors were a group of antidiabetic drugs, which had the ability to reduce the blood sugar via inhibiting SGLT-2 [ 24 ]. Furthermore, except for lowering blood sugar [ 25 – 30 ], SGLT-2 inhibitors also had abilities to lose weight [ 24 , 31 , 32 ], reduce cardiovascular outcomes and mortality risk [ 33 ], and play renal protective effect [ 15 ]. It was also reported that SGLT-2 inhibitors could observably lower the response of inflammatory and smaller infarct size compared with other oral antidiabetic drugs, not dependent on blood sugar control [ 34 ].…”

“…The complexity of T2DM treatment and care were very challenging because they involved the prevention of organ damage and complications [23], including chronic damage and dysfunction of various tissues, especially kidneys [4], blood vessels [5], nerves [6], and heart [7], among SGLT-2 inhibitors were a group of antidiabetic drugs, which had the ability to reduce the blood sugar via inhibiting SGLT-2 [24]. Furthermore, except for lowering blood sugar [25][26][27][28][29][30], SGLT-2 inhibitors also had abilities to lose weight [24,31,32], reduce cardiovascular outcomes and mortality risk [33], and play renal protective effect [15]. It was also reported that SGLT-2 inhibitors could observably lower the response of inflammatory and smaller infarct size compared with other oral antidiabetic drugs, not dependent on blood sugar control [34].…”

A Network Meta-Analysis of the Dose–Response Effects of Dapagliflozin on Efficacy and Safety in Adults With Type 1 Diabetes

“…Ultimately, 13 trials covering results for 10,701 patients (5,669 women and 5,032 men) were involved in the analysis. The mean study duration was 41.54 ± 14.47 weeks (Supplementary Materials Table S1) (15,16,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”