Efficacy and safety of ipragliflozin as an add-on to a sulfonylurea in Japanese patients with inadequately controlled type 2 diabetes: results of the randomized, placebo-controlled, double-blind, phase III EMIT study

Abstract

Sulfonylureas are often used alone or in combination with other drugs for treating type 2 diabetes. Ipragliflozin is a sodium/glucose cotransporter 2 inhibitor that enhances urinary glucose excretion and improves glycemic control. We examined the efficacy and safety of ipragliflozin as an add-on to a sulfonylurea in Japanese type 2 diabetes patients with inadequate glycemic control in a phase III study. Patients were randomized, double-blind, to 50 mg ipragliflozin or placebo for 24 weeks, followed by a 28-week open-label extension in which all patients received either 50 or 100 mg ipragliflozin. The primary endpoint was the change in HbA1c from baseline to week 24 (last observation carried forward). Overall, 166 patients were prescribed ipragliflozin and 77 were prescribed placebo. The adjusted mean change in HbA1c from baseline to week 24 between the ipragliflozin and placebo groups was −1.14 % (P < 0.001). The reductions in fasting plasma glucose and body weight were significantly greater in the ipragliflozin group (placebo-adjusted mean change: −38.0 mg/dl and −1.32 kg, respectively; both, P < 0.001). These changes were maintained until the end of the open-label extension. There were more treatment-emergent adverse events in the ipragliflozin group than in the placebo group (75.9 vs. 61.8 %; P = 0.032). The most common adverse events with a higher incidence in the ipragliflozin group than in the placebo group were mild pollakiuria and thirst. Ipragliflozin as an add-on to a sulfonylurea significantly improved glycemic control and reduced body weight, with good tolerability, in Japanese type 2 diabetes patients.

Primary Investigators

Kazuo Yamagata (Sakajiri Naika Iin), Daishiro Yamada (Jiyugaoka Yamada Clinic of Internal Medicine), Fuminobu Okuguchi (Okuguchi Clinic of Internal Medicine), Takashi Naitou (Saka General Clinic), Hiroaki Seino (Seino Internal Medicine Clinic), Hiroshi Kouno (Jusendo General Hospital), Hirokazu Shoda (Seiwakai Shoda Hospital), Shuichi Fukuda (Wakakusa Clinic), Yoshio Ohashi (Tokyo Ekimae-building Clinic), Madoka Taguchi (Toshiba General Hospital), Mizuki Kaneshiro (Kaneshiro Diabetes Clinic), Koutaro Fujimoto (Fujimoto Clinic), Ikuro Matsuba (Matsuba Clinic), Takaaki Iwai (Sagamino Central Hospital), Akira Yamauchi (Medical Corp. Rikeikai Suruga Clinic), Shizuo Kajiyama (Kajiyama Clinic), Takehiko Kobayashi (Kobayashi Shinryosho), Kiyomitsu Ikeoka (Medical Corp. Ikeoka Clinic), Emi Kose (Sato Hospital), Bunrei Goto (Medical Corp. Gotou Medical Clinic), Kunihiro Ekawa (Saiseikai Wakayama Hospital), Tetsuji Okuno (Nippon Kokan Fukuyama Hospital), Nobuyuki Abe (Abe Diabetes Clinic), Makoto Kunisaki (Kunisaki Makoto Clinic, Medical Corp. Shinaikai), Syuichi Otabe (Otabe Internal Medicine Clinic), Hideaki Jinnouchi (Jinnouchi Hospital), Masahiko Takai (Medical Corp. Takai Internal Medicine Clinic), Tsuguyoshi Asano (Asano Kanamachi Clinic), Kazuo Satake (Fukui General Clinic), Kazunori Yokoyama (Nikko Memorial Hospital), Munenori Okamoto (Sapporo Century Hospital), Tamayuki Koizumi (Medical Corp. Pieta Association Ishikari Hospital), Mitsutoshi Kato (Kato Clinic of Internal Medicine), Osamu Tomonaga (Tomonaga Clinic), and Yasuhiro Hashiguchi (Tenpozan Internal Clinic).