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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: 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.

SUBMITTER: Araki E

PROVIDER: S-EPMC4931206 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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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.

Araki Eiichi E Onishi Yukiko Y Asano Michiko M Kim Hyosung H Ekholm Ella E Johnsson Eva E Yajima Toshitaka T

Journal of diabetes investigation 20160122 4

<h4>Introduction</h4>Dapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated.<h4>Materials and methods</h4>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 insu ...[more]

PMID: 27181422

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Project description:Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (?1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg).Dapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone.ClinicalTrials.gov: NCT00528879.

Project description:IntroductionTo assess the efficacy and safety of vildagliptin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM), inadequately controlled on stable long-acting, intermediate-acting, or pre-mixed insulin, with or without concomitant metformin.MethodsIn this 12-week placebo-controlled study, patients were randomized to receive either vildagliptin 50 mg twice daily (bid) or placebo treatment in a 1:1 ratio. The primary endpoint was change in glycated hemoglobin A1c (HbA1c) from baseline to 12-week endpoint. Secondary endpoints included proportion of patients achieving pre-defined HbA1c targets of ≤6.5%, <7.0%, and HbA1c <7.0% in patients with baseline HbA1c ≤8.0% and change in fasting plasma glucose (FPG) after 12 weeks of treatment. Regular monitoring was performed to record any treatment-emergent adverse events (AEs) and serious adverse events or hypoglycemic episodes.ResultsOf the 156 patients randomized, 96.8% completed the study (vildagliptin, n = 76; placebo, n = 75). Patient demographics and clinical characteristics were comparable between the groups at baseline. Addition of vildagliptin resulted in statistically significant reductions in HbA1c after 12 weeks (-1.01 ± 0.06%), with a between-treatment difference of -0.91 ± 0.09% (p < 0.001). FPG levels reduced from baseline to 12 weeks in the vildagliptin group (-1.2 ± 0.2 mmol/L), with a between-treatment difference of -1.2 ± 0.3 mmol/L which was significant (p < 0.001). The proportion of patients achieving HbA1c targets was higher with vildagliptin treatment for all pre-defined responder rate categories. The overall incidence of AEs was comparable between groups (vildagliptin, 46.2% vs. placebo, 43.6%). The overall incidence of hypoglycemic events was low and all events were self-treatable without using drug therapy. No severe hypoglycemic events were reported.ConclusionTreatment with vildagliptin 50 mg bid as add-on to insulin with or without metformin resulted in statistically significant reductions in HbA1c in Japanese patients with T2DM. Overall, vildagliptin was well tolerated with a safety profile similar to that of placebo in this patient population. ClinicalTrials.gov Identifier, NCT02002221 FUNDING: Novartis Pharma K.K.

Dataset Information

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.

Publications

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.

Similar Datasets

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