Efficacy and tolerability of rosiglitazone and pioglitazone in drug-naïve Japanese patients with type 2 diabetes mellitus: a double-blind, 28 weeks’ treatment, comparative study

Abstract

Objective:

A 28-week, randomized, placebo-controlled study was performed to evaluate efficacy and tolerability of rosiglitazone in Japanese type 2 diabetes patients.

Research and design methods:

373 patients were randomized to rosiglitazone (4–8 mg/day), pioglitazone (15–45 mg/day) or placebo. Agents were titrated to maximum doses at fixed time points in a pre-defined manner. Primary endpoints were superiority of each active treatment compared to placebo in HbA_1c at week 16, and non-inferiority between active agents in HbA_1c at week 28, based on a −0.45% margin.

Results:

At week 16, improvements versus placebo were observed with rosiglitazone 4 mg/day (−0.96%, p < 0.001) and pioglitazone 30 mg/day (−1.26%, p < 0.001). At week 28, rosiglitazone and pioglitazone were associated with significant changes from baseline of −0.94% and −1.35%, respectively and rosiglitazone produced statistically and clinically significant improvement versus placebo (−1.29%, CI: −1.62, −0.97). Pioglitazone also showed significant improvement versus placebo (−1.64%, CI: −1.96, −1.31). Non-inferiority of rosiglitazone (4–8 mg/day) to pioglitazone (30–45 mg/day) was not demonstrated (treatment-difference: −0.41%, 95% CI: −0.64, −0.18).

More patients treated with pioglitazone were withdrawn from the study by adverse events compared with rosiglitazone (14 vs. 4, p = 0.015). Pioglitazone was associated with higher incidences of adverse events relating to edema and weight gain compared with rosiglitazone (edema: 25.2 vs. 11.3%, weight gain: 9.4 vs. 4.4%). There were no reports of ischemic heart disease or congestive heart failure in any treatment group.

Conclusion:

Although non-inferiority to pioglitazone up to 45 mg in efficacy was not shown, rosiglitazone was confirmed to have clinically meaningful efficacy over placebo and fewer fluid-related events than pioglitazone.

Trial registration: ClinicalTrials.gov identifier: NCT00297063.

Key words::

• Japanese
• Pioglitazone
• Rosiglitazone
• Type 2 diabetes

Transparency

Declaration of funding

Funding for this study was provided by GlaxoSmithKline (NCT00297063).

Declaration of financial/other relationship

M.K. and S.M. have disclosed that they have served as medical experts of this study. K.K. has disclosed that he is an advisor for GlaxoSmithKline. M.O. has disclosed that he has served as a member of Cardiovascular Safety Adjudication Committee. R.I. has disclosed that he is an employee and stockholder of GlaxoSmithKline. CMRO peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors would like to acknowledge the editorial assistance of Joanne Auchinachie of MediTech Media, who prepared an initial draft manuscript with funding from GlaxoSmithKline.

The authors would like to thank all of the study investigators and hospital staff at the 42 sites participating in this trial. The authors would like to thank the following primary investigators and study sites for their contribution to the trial: Dr. Koji Ihara of Kiyota Hospital, Dr. Katsutoshi Komori of Odori Clinic of Internal medicine, Dr. Minoru Takeuchi of Kouyou Clinic, Dr. Keita Atoh of Nikko Memorial Hospital, Dr. Toshio Yamagishi of Tohoku Kosai Hospital, Dr. Hiroshi Ohtani of Iwase General Hospital, Dr. Yoshihiro Shimoyama and Dr. Akiko Kuratomi of Kohnan Hospital, Dr. Takeshi Osonoi of Naka Kinen Clinic, Dr. Hideo Takahashi of Minamiakatsuka Clinic, Dr. Hirokazu Shoda of Shoda Hospital, Dr. Takahiko Yamaguchi of Yamaguchi Internal Clinic, Dr. Daigaku Uchida of Kimitsu Chuo Hospital, Dr. Sakae Sekiya of Arai Hospital, Dr. Taro Wasada of Saitamaken Saiseikaikurihashi Hospital, Dr. Mikio Okuda of Fujiminonaika Clinic, Dr. Tetsuya Morishita of Yamamoto Kinen Hospital, Dr. Koji Nakajima and Dr. Michihito Ishioh of Nakajima Clinic, Dr. Masaharu Morohoshi of Sanraku Hospital, Dr. Osamu Iwata of Shiodome Oak Clinic, Dr. Michio Hayashi of Kanto Medical Center NTT EC, Dr. Mitsutoshi Kato of Kato Clinic of Internal Medicine, Dr. Takahiro Yokoyama of Yotsuya Clinic, Dr. Hajime Onda and Dr. Shuro Kondo of Tokyo Clinical Research Organization for Medicine Clinic, Dr. Kenichi Furihata of P-one Clinic, Dr. Akira Yamauchi of Suruga Clinic, Dr. Mafumi Owa of Suwa Red Cross Hospital, Dr. Michio Nakagawa of Matsumoto Nakagawa Hospital, Dr. Toshimasa Kajinami of Nishikyoto Hospital, Dr. Shizuo Kajiyama of Kajiyama Clinic, Dr. Hirohito Takise of Senbon Hospital, Dr.Shigeto Kanada of Osaka Clinical Research Organization for Medicine Clinic, Dr. Keiji Yoshioka of Matsushita Memorial Hospital, Dr. Kiyoshi Takekawa of Takekawa Naika Clinic, Dr. Masafumi Koga of Kinki Central Hospital, Dr. Kunihiro Kawashima of Japanese Red Cross Kobe Hospital, Dr. Takao Shimada of Kobe Century Memorial Hospital, Dr. Koji Manabe of Shigei Medical Research Hospital, Dr. Masahiro Matsumoto of Kitakyushu Municipal Medical Center, Dr. Takashi Eto of PS Clinic and Dr. Makoto Kunisaki of Kunisaki Makoto Clinic.