Safety and efficacy of addition of sitagliptin to rapid-acting insulin secretagogues for glycemic control, including post-prandial hyperglycemia, among Japanese with type 2 diabetes mellitus

Abstract

The safety and efficacy of sitagliptin as add-on therapy to glinides, rapid-acting insulin secretagogues, were evaluated for Japanese patients with type 2 diabetes mellitus. This 52-week study consisted of a 12-week double-blind period, followed by a 40-week open-label period. During the double-blind period, patients were randomized to sitagliptin 50 mg q.d. (S/S group) or placebo (P/S group) as add-on therapy to glinide monotherapy. During the open-label period, all patients in both groups were administered sitagliptin 50 mg q.d. (or 100 mg q.d. after up-titration). During the double-blind period, the overall occurrence of adverse experiences (AE) was similar in both treatment groups. The frequency of reported AE of hypoglycemia in both groups was low and not notably different. The nature of clinical AE during the open-label period for both groups was not notably different from that of clinical AE in the sitagliptin group during the double-blind period. The between-group difference in HbA1c least squares (LS) mean of change from baseline (95 % CI) at Week 12 was −1.1 % (−1.3, −0.8) in favor of sitagliptin (P < 0.001). LS mean of reductions from baseline of fasting plasma glucose and 2-h postmeal glucose were significantly greater in the sitagliptin group than in the placebo group: −23.1 mg/dL (−32.2, −13.9) and −51.2 mg/dL (−67.4, −35.0), respectively (both P < 0.001). The changes from baseline in glycemic data in the S/S group remained generally stable throughout the 52-week treatment period.

Appendix 1

MK-0431 P282/ONO-5435-17 Primary Investigator list: Fuminobu Okuguchi (Okuguchi Clinic of Internal Medicine), Naoki Itabashi (Itabashi Clinic), Tomoyuki Arisaka (Arisaka Clinic), Takashi Ishii (Ishii Hospital), Yuichiro Makita (Koshigaya Municipal Hospital), Yoshihiko Suzuki (HDC Atlas Clinic), Yukiko Onishi (The Institute for Adult Diseases, Asahi Life Foundation), Masaharu Morohoshi (Sanraku Hospital, Lifestyle Diseases Clinic), Arihiro Kiyosue (Tokyo-Eki Center-Building Clinic), Masayo Yamada (Yokohama Sakae Kyosai Hospital), Taro Asakura (Tsuruma Kaneshiro Diabetes Clinic), Shin-ichiro Matsumura (Yokohama Cardiopulmonary Clinic), Ichitaro Takada (Takada Naika Clinic), Toshio Kiguchi (Kiguchi Clinic), Masaaki Ohashi (Saku Central Hospital), Akira Yamauchi (Suruga Clinic), Hideki Okamoto (Meitetsu Hospital), Genichi Watanabe (Watanabe Clinic), Mikihiro Nakayama (Nakayama Clinic), Masako Deguchi (Japanese Red Cross Kyoto Daini Hospital), Yasuro Kumeda (Minamiosaka Hospital), Soichi Kurioka (Komatsu Hospital), Takashi Ikawa (Osaka Rehabilitation Hospital), Kazushige Ejiri (Joyo Ejiri Hospital), Hidenori Ohno (Oofuji Clinic), Atsuyoshi Yuhara (Yuhara Clinic), Akira Matsutani (Shunan City Shin-nanyo Hospital), Makoto Kunisaki (Kunisaki Makoto Clinic), Shoichi Akazawa (Shinkoga Clinic), and Noriko Nakamura (Primula Clinic).