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
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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.
KeywordsAdd-on Sitagliptin Incretins Glinide Type 2 diabetes mellitus
The authors would like to thank M. Kawashima, D. Yanagida, M. Ohkubo, H. Shuno, M. Kondo, H. Suna, H. Maekawa, T. Yoshida, T. Kuramoto, S. Shiono, Y. Hatori, K. Nagasawa, Y. Kamehara, N. Inaba, and M. Odani (ONO Pharmaceutical Co., Ltd., Japan) for their assistance in writing and preparing this paper for submission and publication.
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Conflict of interest
Authors Tajima and Kadowaki were coordinating investigators for this study. Author Odawara was the medical advisor for this study. Author Tajima has acted as advisory panel for Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd. and Sanofi K.K.; as consultant for MSD K.K. and Ono Pharmaceutical Co., Ltd.; as a speaker for Astellas Pharma Inc., Daiichi-Sankyo, Co., Ltd., Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan Inc., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. and Dainippon Sumitomo Pharma Co., Ltd. Author Kadowaki has acted as advisory panel for AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., and Takeda Pharmaceutical Co., Ltd.; as consultant for MSD K.K., and Ono Pharmaceutical Co., Ltd.; as a speaker for Astellas Pharma, Inc., AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan K.K., Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corp., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; obtained research support from Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., MSD K.K., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., and Takeda Pharmaceutical Co., Ltd.; and has been involved in research units endowed by MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Co., Ltd., and Terumo Corp. Author Odawara has acted as consultant for MSD K.K. and Ono Pharmaceutical Co., Ltd.; as a speaker for MSD K.K. and Ono Pharmaceutical Co., Ltd.. Authors Minamide, Seki, and Oki are full-time employees of ONO Pharmaceutical Co., Ltd., Japan and authors Nagayasu is a full-time employee of MSD K.K.and Arjona Ferreira was a full-time employee of Merck Sharp & Dohme Corp. at the time of the study, and might potentially own stock and/or hold stock options in the company. No other potential conflicts of interest relevant to this article were reported. This study was sponsored by MSD K.K., Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, the manufacturer of sitagliptin, and by Ono Pharmaceutical Co. Ltd., Japan.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later revision. Informed consent or substitute for it was obtained from all patients included in the study.
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