Safety and Tolerability of Empagliflozin in East Asian Patients with Type 2 Diabetes—Pooled Analysis of Phase I-III Clinical Trials

Abstract

Aims/Introduction: As the pathophysiology of type 2 diabetes (T2DM) differs in East Asian patients compared with that in other ethnic groups, a comprehensive evaluation of the safety of empagliflozin (EMPA) in East Asian patients is desirable to inform clinical practice in the patient population. We therefore investigated the safety and tolerability of EMPA in East Asian patients with T2DM. Materials and Methods: Data were pooled from patients with T2DM treated with placebo, EMPA 10 mg or 25 mg in 15 Phase I-III trials plus 4 extension studies. Adverse events (AEs) were analyzed in the subgroup of patients from East Asian countries. (China, Hong Kong, Japan, Korea, Taiwan) (N=2141). Results: Total exposure was 953, 1072, and 1033 patient-years in the placebo, EMPA 10 mg, and 25 mg groups, respectively. The incidence of any AEs, severe AEs, serious AEs, and AEs leading to discontinuation was no higher in patients who were treated with either dose of EMPA than in those treated with placebo. The incidence of hypoglycemia differed according to glucose-lowering medications used at baseline. Events consistent with urinary tract infection occurred less frequently with EMPA than placebo (5.3-5.8 vs. 7.2/100 patient-years). Events consistent with genital infection occurred more frequently with EMPA than placebo (1.5-1.7 vs. 0.2/100 patient-years). The incidence of AEs consistent with volume depletion was similar across treatment groups (0.8-1.4/100 patient-years). Rates of bone fractures, renal AEs, venous thromboembolic events, hepatic injury, lower limb amputation and diabetic ketoacidosis were similar or no higher with EMPA vs. placebo. Conclusions: In this pooled analysis, EMPA was well tolerated in the East Asian patients with T2DM based on >3,000 patient-years’ exposure, consistent with results from the overall analysis population. The result was in line with package inserts in East Asian countries and did not raise new safety concerns. Disclosure A. Yasui: Employee; Self; Nippon Boehringer Ingelheim Co. Ltd. D. Yabe: Speaker's Bureau; Self; MSD K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd.. Research Support; Self; Nippon Boehringer Ingelheim Co. Ltd., Eli Lilly and Company, MSD K.K., Ono Pharmaceutical Co., Ltd., Arkray, Inc., Taisho Toyama Pharmaceutical Co., Ltd., Novo Vordisk Pharma Ltd., Takeda Pharamaceutical Co., Ltd. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Eli Lilly and Company, Bristol-Myers Squibb Company, Novartis AG, Novo Nordisk A/S, Merck & Co., Inc., Bayer AG, Merck Sharp & Dohme Corp., Takeda Development Center Asia, Pte. Ltd., Sanofi, Roche Pharma, Boehringer Ingelheim GmbH. Research Support; Self; AstraZeneca, Roche Pharma, Sanofi, Merck Sharp & Dohme Corp., Novartis AG, Eli Lilly and Company, Bristol-Myers Squibb Company. M. Lee: None. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd. T. Chang: Stock/Shareholder; Self; Novo Nordisk A/S. Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd. T. Okamura: Employee; Self; Nippon Boehringer Ingelheim Co. Ltd. C. Zeller: Employee; Self; Boehringer Ingelheim Pharma GmbH & Co. KG. S. Kaspers: Employee; Self; Boehringer Ingelheim GmbH. J. Lee: Employee; Self; Boehringer Ingelheim GmbH. S. Kohler: Employee; Self; Boehringer Ingelheim GmbH. Y. Seino: Speaker's Bureau; Self; MSD K.K., Kao Corporation, Taisho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Taisho Toyama Pharamceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Becton Dickinson Co., Ltd., Novo Nordisk Pharma Ltd.. Research Support; Self; Terumo Medical Corporation, Bayer Yakuhin, Ltd., Boehringer Ingelheim GmbH, Arkray, Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd..