Efficacy and Safety of a SinglePill Combination o

Authors: Masato Odawara Mika Yoshiki Misako Sano Izumi Hamada Valentina Lukashevich Wolfgang Kothny

Publish Date: 2015/02/18

Volume: 6, Issue: 1, Pages: 17-27

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Abstract

The use of dipeptidyl peptidase4 inhibitors in combination with metformin is increasing in Japanese patients with type 2 diabetes mellitus T2DM but no singlepill combination SPC is currently available in Japan The objective of this study was to assess the efficacy and safety of vildagliptin/metformin SPC in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapyThis was a 14week randomized doubleblind parallelgroup placebocontrolled trial 171 patients with T2DM inadequately controlled HbA1c glycosylated hemoglobin 70–100 with vildagliptin 50 mg twice daily bid were randomized 21 to receive either a vildagliptin/metformin SPC n = 115 or matching vildagliptin/placebo SPC n = 56Baseline demographics and background characteristics were generally comparable between the treatment groups The change in HbA1c mean ± standard error SE was −08 ± 01 in the vildagliptin/metformin SPC baseline HbA1c 79 ± 01 group and 01 ± 01 in the vildagliptin/placebo SPC baseline HbA1c 80 ± 01 group with a betweentreatment difference of −10 ± 01 P 0001 in favor of the vildagliptin/metformin SPC group The proportion of patients achieving target HbA1c 70 was significantly higher with vildagliptin/metformin SPC compared with vildagliptin/placebo SPC 458 vs 135 P 0001 The overall incidences of adverse events AEs were 435 in the vildagliptin/metformin SPC and 679 in the vildagliptin/placebo SPC group The incidences of serious AEs were low in both the treatment groups 09 vs 36 respectively Body weight remained constant throughout the study in both the treatment groups There were no deaths or hypoglycemic events during the studySwitching Japanese patients with T2DM requiring treatment intensification from vildagliptin monotherapy to a vildagliptin/metformin SPC 50/250 or 50/500 mg was efficacious and safe eliciting significant reduction in HbA1c without increased risk of hypoglycemia and weight gainThe worldwide prevalence of type 2 diabetes mellitus T2DM continues to rise dramatically with Asian countries contributing more than half of the world’s diabetic population 1 2 Currently 72 million individuals aged between 20 and 79 years are affected by T2DM in Japan 1 T2DM clinical practice guidelines by the American Diabetes Association 3 and International Diabetes Federation 4 suggest starting treatment with metformin unless contraindicated followed by the addition of other oral antidiabetic drugs OADs if patients fail to achieve glycosylated hemoglobin HbA1c goal 70 The Japan Diabetes Society JDS suggests starting pharmacotherapy with any OAD depending on the physiological status of the patient after diet and exercise failure 5 Most of the Japanese patients with T2DM have a tendency to a low body mass index BMI and as insulin secretion deficiency plays a predominant role in disease pathology 6 insulin secretagogues are the preferred firstline treatment option in Japan Recently Japanese patients with T2DM are being increasingly treated with dipeptidyl peptidase4 DPP4 inhibitors eg vildagliptin 7 which increase insulin secretion from βcells in a glucosedependent manner 8 Moreover the progressive nature of the disease warrants treatment intensification with other antidiabetic agents having complementary mechanism of action to maintain glycemic control over long term 5The mechanistic synergy between vildagliptin and metformin 8 9 and the efficacy and safety of vildagliptin added to metformin in Japanese patients with T2DM inadequately controlled with metformin monotherapy has already been demonstrated 10 However the benefit of switching patients who are treated with vildagliptin and require additional treatment to vildagliptin and metformin has not been established So far no DPP4 inhibitor/metformin singlepill combination SPC is available in Japan Such a SPC has the additional benefit of a reduced pill burden and potentially better compliance 11 Moreover the efficacy of lowdose metformin 250 mg twice daily bid has not been studied previously in a randomized trial setting in Japanese patients with T2DM Accordingly the current study was aimed to assess the efficacy and safety of vildagliptin/metformin SPC at doses of 50/250 and 50/500 mg in Japanese patients with T2DM inadequately controlled with diet exercise and vildagliptin monotherapy

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