BMJ Open Diabetes Research & Care (Aug 2021)

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

  • Masakazu Kobayashi,
  • Hirohito Sone,
  • Haruhiko Osawa,
  • Daisuke Koya,
  • Takanori Miura,
  • Yoshihito Atsumi,
  • Udai Nakamura,
  • Eiichi Araki,
  • Hitoshi Shimano,
  • Yukio Tanizawa,
  • Jiro Nakamura,
  • Yuichiro Yamada,
  • Nobuya Inagaki,
  • Atsuko Abiko,
  • Hideki Katagiri,
  • Michio Hayashi,
  • Keiko Naruse,
  • Shimpei Fujimoto,
  • Masazumi Fujiwara,
  • Kenichi Shikata,
  • Yosuke Okada,
  • Tsutomu Yamazaki,
  • Sou Nagai,
  • Katsuyuki Yanagisawa,
  • Hiromichi Kijima,
  • Shinji Taneda,
  • Shigeyuki Saitoh,
  • Daisuke Ikeda,
  • Fuminori Hirano,
  • Haruhiko Yoshimura,
  • Mitsutaka Inoue,
  • Masahiko Katoh,
  • Osamu Nakagaki,
  • Chiho Yamamoto,
  • Akitsuki Morikawa,
  • Shin Furukawa,
  • Takeshi Koshiya,
  • Hajime Sugawara,
  • Takumi Uchida,
  • Noe Takakubo,
  • Yasushi Ishigaki,
  • Susumu Suzuki,
  • Takashi Shimotomai,
  • Naoki Tamasawa,
  • Jun Matsui,
  • Takashi Goto,
  • Toshihide Oizumi,
  • Shinji Susa,
  • Makoto Daimon,
  • Hiroshi Murakami,
  • Takashi Sugawara,
  • Hiroaki Akai,
  • Mari Nakamura,
  • Yoshiji Ogawa,
  • Takao Yokoshima,
  • Tsuyoshi Watanabe,
  • Michio Shimabukuro,
  • Kazuhisa Tsukamoto,
  • Motoei Kunimi,
  • Jo Satoh,
  • Atushi Okuyama,
  • Kazutaka Ogawa,
  • Hideyuki Eguchi,
  • Mamoru Kimura,
  • Hiroshi Kouno,
  • Yohei Horikawa,
  • Shin Ikejima,
  • Masaru Saitoh,
  • Naoyoshi Minami,
  • Akihiro Sekikawa,
  • Toyoyoshi Uchida,
  • Toshihide Kawai,
  • Nobuya Fujita,
  • Ken Tomotsune,
  • Shigeo Yamashita,
  • Motoji Naka,
  • Toru Hiyoshi,
  • Tomotaka Katoh,
  • Kumiko Hamano,
  • Kouichi Inukai,
  • Takuma Kondo,
  • Kazuhiro Tsumura,
  • Yoko Matsuzawa,
  • Masahiro Mimura,
  • Masahiko Kawasumi,
  • Izumi Takei,
  • Masafumi Matsuda,
  • Ichiro Tatsuno,
  • Nobuyuki Banba,
  • Akihiko Ando,
  • Masao Toyoda,
  • Daisuke Suzuki,
  • Takahiro Iijima,
  • Yasumichi Mori,
  • Yutaka Uehara,
  • Yoshihiko Satoh,
  • Kazuaki Yahata,
  • Yoshimasa Asoh,
  • Koichiro Kuwabara,
  • Souichi Takizawa,
  • Yasushi Tanaka,
  • Koutaroh Yokote,
  • Masako Tohgo,
  • Takanobu Itoi,
  • Shigeru Miyazaki,
  • Hiroshi Itoh,
  • Teruo Shiba,
  • Takahisa Hirose,
  • Mariko Higa,
  • Masanobu Yamada,
  • Osamu Ogawa,
  • Masatoshi Kuroki,
  • Shinobu Satoh,
  • Makoto Ujihara,
  • Kenjiroh Yamanaka,
  • Hajime Koyano,
  • Tadashi Yamakawa,
  • Kenichiroh Takahashi,
  • Kazuki Orime,
  • Tsutomu Hirano,
  • Jiroh Morimoto,
  • Takashi Itoh,
  • Yuzoh Mizuno,
  • Naoyuki Yamamoto,
  • Han Miyatake,
  • Mina Yamaguchi,
  • Kenji Yamane,
  • Masahiko Kure,
  • Satoko Kawabe,
  • Masahumi Kakei,
  • Masashi Yoshida,
  • Hiroyuki Itoh,
  • Nobuaki Minami,
  • Kazuki Kobayashi,
  • Yusuke Fujino,
  • Makoto Shibuya,
  • Midori Hosokawa,
  • Isao Nozaki,
  • Chigure Nawa,
  • Tamio Ieiri,
  • Takayuki Watanabe,
  • Yoshio Katoh,
  • Takuyuki Katabami,
  • Michiko Handa,
  • Issei Shimada,
  • Kenichi Ohya,
  • Yoshihiro Ogawa,
  • Takanobu Yoshimoto,
  • Jiroh Nakamura,
  • Naotsuka Okayama,
  • Kenro Imaeda,
  • Syuko Yoshioka,
  • Masako Murakami,
  • Takashi Murase,
  • Yoshihiko Yamada,
  • Yutaka Yano,
  • Hiromitsu Sasaki,
  • Yasuhiro Sumida,
  • Osamu Yonaha,
  • Hiroshi Sobajima,
  • Mitsuyasu Ito,
  • Atushi Suzuki,
  • Atsuko Ishikawa,
  • Takehiko Ichikawa,
  • Shogo Asano,
  • Shinobu Goto,
  • Sakuma Hiroya,
  • Hiroshi Murase,
  • Shozo Ogawa,
  • Hideki Okamoto,
  • Kotaro Nagai,
  • Koji Nagayama,
  • Masanori Yoshida,
  • Norio Takahashi,
  • Kazuhisa Takami,
  • Tsuneo Ono,
  • Takanobu Morihiro,
  • Daisuke Tanaka,
  • Noriko Takahara,
  • Satoshi Miyata,
  • Mamiko Tsugawa,
  • Koichiro Yasuda,
  • Seiji Muro,
  • Masanori Emoto,
  • Ikuo Mineo,
  • Ichiro Shiojima,
  • Takeshi Kurose,
  • Makoto Ohashi,
  • Yumiko Kawabata,
  • Mitsushige Nishikawa,
  • Emiko Nomura,
  • Yasuyuki Nishimura,
  • Yasuhiro Ono,
  • Yasuhisa Yamamoto,
  • Keigo Naka,
  • Taizo Yamamoto,
  • Rika Usuda,
  • Hiroshi Akahori,
  • Seika Kato,
  • Hiroyuki Konya,
  • Yutaka Umayahara,
  • Takashi Seta,
  • Hideki Taki,
  • Masashi Sekiya,
  • Shinichi Mogami,
  • Sumie Fujii,
  • Toshiyuki Hibuse,
  • Shingo Tsuji,
  • Hirofumi Sumi,
  • Yasuro Kumeda,
  • Akinori Kogure,
  • Kenji Furukawa,
  • Akira Kuroe,
  • Hideaki Sawaki,
  • Narihiro Hibiki,
  • Yoshihiro Kitagawa,
  • Yukihiro Bando,
  • Akira Ono,
  • Rikako Uenaka,
  • Seitaro Omoto,
  • Yuki Kita,
  • Eiko Ri,
  • Ryutaro Numaguchi,
  • Sachiko Kawashima,
  • Ichiro Kisimoto,
  • Kiminori Hosoda,
  • Yoshihiko Araki,
  • Tetsuroh Arimura,
  • Mitsuru Hashiramoto,
  • Koumei Takeda,
  • Akira Matsutani,
  • Yasushi Inoue,
  • Fumio Sawano,
  • Nozomu Kamei,
  • Yasuo Ito,
  • Miwa Morita,
  • Yoshiaki Oda,
  • Rui Kishimoto,
  • Katsuhiro Hatao,
  • Tomoatsu Mune,
  • Fumiko Kawasaki,
  • Hiroki Teragawa,
  • Ken Yaga,
  • Keita Ishii,
  • Kyouji Hirata,
  • Tatsuaki Nakatou,
  • Yutaka Nitta,
  • Naoki Fujita,
  • Masayasu Yoneda,
  • Masatoshi Tsuru,
  • Shinichirou Ando,
  • Toshiaki Kakiba,
  • Michihiro Toyoshige,
  • Tsuguka Shiwa,
  • Hiroaki Miyaoka,
  • Yasumi Shintani,
  • Takenori Sakai,
  • Tetsuji Niiya,
  • Shinpei Fujimoto,
  • Hisaka Minami,
  • Yoshihiko Noma,
  • Masaaki Tamaru,
  • Yoshitaka Sayou,
  • Tomoyo Oyama,
  • Masamoto Torisu,
  • Yuichi Fujinaka,
  • Yoshitaka Kumon,
  • Shozo Miyauchi,
  • Morikazu Onji,
  • Toru Nakamura,
  • Yousuke Okada,
  • Toshihiko Yanase,
  • Kenro Nishida,
  • Syuji Nakamura,
  • Kunihisa Kobayashi,
  • Nobuhiko Wada,
  • Moritake Higa,
  • Koji Matsushita,
  • Yoshihiko Nishio,
  • Ryoji Fujimoto,
  • Yasuyuki Kihara,
  • Shinichiro Mine,
  • Tadashi Arao,
  • Hiromi Tasaki,
  • Yasuto Matsuo,
  • Hirofumi Matsuda,
  • Kohei Uriu,
  • Kazuko Kanda,
  • Kazuo Ibaraki,
  • Yoshio Kaku,
  • Yasuhiro Takaki,
  • Iwaho Hazekawa,
  • Kenji Ebihara,
  • Eiichiro Watanabe,
  • Iku Sakurada,
  • Kazuhisa Muraishi,
  • Tamami Oshige,
  • Junichi Yasuda,
  • Toyoshi Iguchi,
  • Noriyuki Sonoda,
  • Masahiro Adachi,
  • Isao Ichino,
  • Yuko Horiuchi,
  • Souichi Uekihara,
  • Shingo Morimitsu,
  • Mitsuhiro Nakazawa,
  • Tadashi Seguchi,
  • Kengo Kaneko

DOI
https://doi.org/10.1136/bmjdrc-2020-001787
Journal volume & issue
Vol. 9, no. 1

Abstract

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Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.