PMID- 26718606 OWN - NLM STAT- MEDLINE DCOM- 20160914 LR - 20221207 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 38 IP - 1 DP - 2016 Jan 1 TI - Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 Inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus. PG - 66-88.e20 LID - S0149-2918(15)01215-1 [pii] LID - 10.1016/j.clinthera.2015.10.025 [doi] AB - PURPOSE: To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin (TS-071) in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Study 1 was a 52-week, Phase III study to evaluate the efficacy and safety of 2.5 mg/d luseogliflozin (or increased to 5 mg/d) in patients with T2DM with moderate renal impairment. During the initial 24 weeks, efficacy and safety of luseogliflozin were compared with placebo. Study 2 was a pooled analysis of four 52-week, Phase III studies of luseogliflozin, including Study 1, to evaluate the efficacy and safety of luseogliflozin in patients with various degrees of renal function. Patients were stratified into 3 groups by baseline estimated glomerular filtration rate (eGFR): normal renal function (>/=90 mL/min/1.73 m(2)), mild impairment (>/=60 to <90 mL/min/1.73 m(2)), and moderate impairment (>/=30 to <60 mL/min/1.73 m(2)). Patients with moderate impairment were further divided into those with mild-moderate (>/=45 to <60 mL/min/1.73 m(2)) and moderate-severe (>/=30 to <45 mL/min/1.73 m(2)). In both studies, efficacy end points included changes in glycated hemoglobin (HbA1c) level, fasting plasma glucose (FPG) level, and body weight. The safety end points included adverse events (AEs) and laboratory parameters. FINDINGS: In Study 1, HbA1c, FPG, and body weight significantly decreased at Week 24 in patients treated with luseogliflozin compared with patients treated with placebo, with the decrease in these parameters also observed with luseogliflozin at Week 52. The incidence of AEs was similar between groups. In Study 2, 1030 patients were included (normal, 275; mildly impaired, 598; and moderately impaired, 157). At Week 52, HbA1c, FPG, and body weight were significantly decreased from baseline in all groups. In between-group comparisons, the decreases in HbA1c and body weight were significantly smaller in patients with moderate impairment than in those with normal function; however, the HbA1c-lowering efficacy was reduced by nearly half, whereas the efficacy of body weight lowering was not so much diminished in the moderate impairment group. Furthermore, a scatter plot showed that changes in HbA1c were more influenced by baseline HbA1c than by baseline eGFR. The incidence of AEs during 52 weeks was similar among all groups, with the majority being mild. IMPLICATIONS: Luseogliflozin improved glycemic control and reduced body weight in all eGFR groups, and its efficacy on HbA1c lowering was reduced in those with moderate renal impairment. Luseogliflozin was well tolerated and safe, with no significant safety issues identified, regardless of baseline eGFR. The study is registered with Clinical Trials Information/JapicCTI of the Japan Pharmaceutical Information Center, and the study registry identification numbers are JapicCTI-111507, JapicCTI-111508, JapicCTI-111509, and JapicCTI-111543. CI - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Haneda, Masakazu AU - Haneda M AD - Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan. Electronic address: haneda@asahikawa-med.ac.jp. FAU - Seino, Yutaka AU - Seino Y AD - Kansai Electric Power Hospital, Osaka, Japan. FAU - Inagaki, Nobuya AU - Inagaki N AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Kaku, Kohei AU - Kaku K AD - Department of Internal Medicine, Kawasaki Medical University, Okayama, Japan. FAU - Sasaki, Takashi AU - Sasaki T AD - Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Chiba, Japan. FAU - Fukatsu, Atsushi AU - Fukatsu A AD - Yachiyo Hospital, Aichi, Japan. FAU - Kakiuchi, Haruka AU - Kakiuchi H AD - Taisho Pharmaceutical Co. Ltd., Tokyo, Japan. FAU - Sato, Yuri AU - Sato Y AD - Taisho Pharmaceutical Co. Ltd., Tokyo, Japan. FAU - Sakai, Soichi AU - Sakai S AD - Taisho Pharmaceutical Co. Ltd., Tokyo, Japan. FAU - Samukawa, Yoshishige AU - Samukawa Y AD - Taisho Pharmaceutical Co. Ltd., Tokyo, Japan. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20151222 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transport Proteins) RN - 506T60A25R (Sorbitol) RN - C596HWF74Z (1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol) SB - IM MH - Adult MH - Aged MH - Blood Glucose/analysis MH - Body Weight MH - Diabetes Mellitus, Type 2/blood/complications/*drug therapy MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Glomerular Filtration Rate MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Japan MH - Male MH - Middle Aged MH - Renal Insufficiency/complications/*physiopathology MH - Sodium-Glucose Transport Proteins/antagonists & inhibitors MH - Sorbitol/adverse effects/*analogs & derivatives/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Japanese OT - glomerular filtration rate OT - luseogliflozin OT - renal impairment OT - sodium glucose cotransporter 2 inhibitor OT - type 2 diabetes mellitus EDAT- 2016/01/01 06:00 MHDA- 2016/09/15 06:00 CRDT- 2016/01/01 06:00 PHST- 2015/06/19 00:00 [received] PHST- 2015/09/11 00:00 [revised] PHST- 2015/10/27 00:00 [accepted] PHST- 2016/01/01 06:00 [entrez] PHST- 2016/01/01 06:00 [pubmed] PHST- 2016/09/15 06:00 [medline] AID - S0149-2918(15)01215-1 [pii] AID - 10.1016/j.clinthera.2015.10.025 [doi] PST - ppublish SO - Clin Ther. 2016 Jan 1;38(1):66-88.e20. doi: 10.1016/j.clinthera.2015.10.025. Epub 2015 Dec 22.