Efficacy and safety of dapagliflozin in addition to insulin therapy in Japanese patients with type 2 diabetes: Results of the interim analysis of 16‐week double‐blind treatment period

Abstract

IntroductionDapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated.Materials and MethodsThis was a multicenter, randomized, double‐blind, parallel‐group, placebo‐controlled study to evaluate efficacy (at 16 weeks) and long‐term safety (at 52 weeks) of dapagliflozin in addition to insulin therapy. The interim analysis was carried out at week 16 to assess the efficacy and safety profiles. The patients receiving insulin (n = 182) were randomized to either dapagliflozin 5 mg or a placebo at a 2:1 ratio. The primary efficacy end‐point was the change in hemoglobin A1c (HbA1c) from baseline at week 16.ResultsPatients in the dapagliflozin group showed an adjusted decrease in HbA1c of −0.55% from baseline, whereas the placebo showed a marginal increase of 0.05%. The placebo‐corrected mean change of HbA1c from baseline to week 16 in dapagliflozin was −0.60% (P < 0.0001). In addition, the placebo‐corrected mean change of fasting plasma glucose and bodyweight from baseline to week 16 in the dapagliflozin group was −22.7 mg/dL (P < 0.0001) and −1.21 kg (P < 0.0001), respectively. The placebo‐corrected mean daily insulin dose in the dapagliflozin group was numerically decreased (treatment difference: −0.72 IU/day; P = 0.0743). No major episodes or discontinuations as a result of hypoglycemia were reported during the study period.ConclusionsDapagliflozin used as add‐on treatment to insulin therapy showed significantly greater reduction of HbA1c, fasting plasma glucose and bodyweight without severe hypoglycemia compared with the placebo at week 16. These results show the clinical benefit of prescribing dapagliflozin for Japanese patients with insufficient glycemic control even with insulin therapy.

Dapagliflozin as add‐on therapy in Asian patients with type 2 diabetes inadequately controlled on insulin with or without oral antihyperglycemic drugs: A randomized controlled trial

“…This risk is further increased with the use of SGLT2 inhibitors, likely due to increased glucosuria . The reported incidence of genital infections and UTIs was lower in the present study than in comparable studies in other populations; however, similar results have been reported in other studies of SGLT2 inhibitors in Asian populations . Adverse events of renal function were infrequent in both treatment groups (2.2% and 3.8% for dapagliflozin and placebo, respectively), and were primarily reported in relation to variation in blood creatinine values in protocol‐mandated regular laboratory checks without clinically symptomatic AEs.…”

“…Most of the study population was Chinese (82%), potentially limiting the generalizability of the study findings to other Asian populations or the overall Asian population. However, similar results have been observed in a study of Japanese patients receiving dapagliflozin as add‐on to insulin, a pooled analysis of dapagliflozin as monotherapy or add‐on therapy to OADs in broader Asian populations, and in studies of other SGLT2 inhibitors plus insulin in Japanese populations . The short duration of the study (24 weeks) does not allow assessment of the durability of the observed effects.…”

Sodium–glucose cotransporter 2 inhibitor, tofogliflozin, shows better improvements of blood glucose and insulin secretion in patients with high insulin levels at baseline

“…In contrast, the recently reported Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients‐Removing Excess Glucose trial showed no difference in the benefits of SGLT2 inhibitor on cardiovascular disease prevention between the patients with insulin therapy and those without insulin therapy. Thus, insulin injection combined with SGLT2 inhibitors for those patients is then considered from the perspective of efficacy and safety, although the insulin secretory capacity of those patients might be lower. Before prescribing the SGLT2 inhibitor, checking the insulin requirement of those patients seems to be necessary.…”

Comparison between sodium–glucose cotransporter 2 inhibitors and pioglitazone as additions to insulin therapy in type 2 diabetes patients: A systematic review with an indirect comparison meta‐analysis

“…Figure b shows the changes in FPG levels from baseline, which were assessed in four PIO studies ( n = 1,116) and six SGLT2i studies ( n = 1,683). Both the PIO/INS and SGLT2i/INS groups showed significantly reduced FPG levels compared with the respective PCB/INS group ( P < 0.001 for both).…”