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

• Published in: Journal of diabetes investigation Vol. 7; no. 4; pp. 555 - 564
• Main Authors: Araki, Eiichi, Onishi, Yukiko, Asano, Michiko, Kim, Hyosung, Ekholm, Ella, Johnsson, Eva, Yajima, Toshitaka
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.07.2016; John Wiley and Sons Inc
• Subjects: Add on to insulin; Aged; Antidiabetics; Asian Continental Ancestry Group; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - therapeutic use; Blood Glucose - drug effects; Body Weight - drug effects; Clinical Trial; Dapagliflozin; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Double-Blind Method; Double-blind studies; Drug Therapy, Combination; Fasting; Female; Glucose; Glucosides - adverse effects; Glucosides - therapeutic use; Glycated Hemoglobin A - analysis; Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - adverse effects; Insulin - therapeutic use; Insulin resistance; Japan; Laboratory testing; Male; Middle Aged; Patients; Pharmaceuticals; Safety; Sodium‐glucose co‐transporter 2 inhibitor; Treatment Outcome; Urinary tract diseases; Urinary tract infections; Urogenital system; Japan; Dapagliflozin; Sodium-glucose co-transporter 2 inhibitor; Add on to insulin
• ISSN: 2040-1116; 2040-1124
• DOI: 10.1111/jdi.12453

Introduction Dapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated. Materials and Methods This 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. Results Patients 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. Conclusions Dapagliflozin 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.