Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial

다국어 초록 (Multilingual Abstract)

Background: This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.
Methods: This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea.
Results: Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection.
Conclusion: Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.

참고문헌 (Reference)

1 Halban PA, "β-Cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment" 37 : 1751-1758, 2014

2 Korean Diabetes Association, "Treatment guideline for diabetes. 5th ed"

3 Abdullah N, "The architecture of risk for type 2 diabetes: understanding Asia in the context of global findings" 2014 : 593982-, 2014

4 김대중, "The Epidemiology of Diabetes in Korea" 대한당뇨병학회 35 (35): 303-308, 2011

5 Wright EM, "Renal Na(+)-glucose cotransporters" 280 : F10-18, 2001

6 Kashiwagi A, "Randomized, placebo-controlled, double-blind glycemic control trial of novel sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus" 5 : 382-391, 2014

7 Inzucchi SE, "Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes" 38 : 140-149, 2015

8 Korean Diabetes Association, "Korean diabetes fact sheet 2015"

9 Hedrington MS, "Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes" 11 : 613-623, 2015

10 Kashiwagi A, "Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study" 17 : 304-308, 2015

11 Kashiwagi A, "Ipragliflozin improves glycemic control in Japanese patients with type 2 diabetes mellitus: the BRIGHTEN study" 6 : 8-18, 2015

12 Kurosaki E, "Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data" 139 : 51-59, 2013

13 Lu CH, "Efficacy, safety, and tolerability of ipragliflozin in Asian patients with type 2 diabetes mellitus and inadequate glycemic control with metformin: results of a phase 3 randomized, placebo-controlled, double-blind, multicenter trial" 7 : 366-373, 2016

14 Wilding JP, "Efficacy and safety of ipragliflozin in patients with type 2 diabetes inadequately controlled on metformin: a dosefinding study" 15 : 403-409, 2013

15 Yang W, "Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure: a randomized controlled trial" 8 : 796-808, 2016

16 Cefalu WT, "Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU):52 week results from a randomised, double-blind, phase 3 noninferiority trial" 382 : 941-950, 2013

17 Baker WL, "Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis" 8 : 262-275, 2014

18 Yoon YS, "Differences in the associations of anthropometric measures with insulin resistance and type 2 diabetes mellitus between Korean and US populations: comparisons of representative nationwide sample data" 10 : 642-651, 2016

19 Chan JC, "Diabetes in Asia: epidemiology, risk factors, and pathophysiology" 301 : 2129-2140, 2009

20 Kaku K, "Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: an open-label study" 5 : 415-433, 2014

21 Ji L, "Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study" 36 : 84-100.e9, 2014

22 Ridderstrale M, "Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial" 2 : 691-700, 2014

23 Kim DJ, "Clinical characteristics of Korean type 2 diabetic patients in 2005" 77 (77): S252-257, 2007

24 Fonseca VA, "Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus" 27 : 268-273, 2013