Relationship between Canagliflozin, Sodium Glucose Cotransporter 2 Inhibitor, and Hematopoietic Effects in Patients with Diabetes and Mild Heart Failure: Results from the CANDLE Trial

Daisaku Nakatani, Tomoharu Dohi, Shungo Hikoso, Atsushi Tanaka, Mamoru Nanasato, Wataru Shimizu, Koichi Node, Yasushi Sakata, Masayoshi Ajioka, Junya Ako, Rie Amano, Toshihisa Anzai, Mitsutoshi Asai, Kaoru Dohi, Kazuo Eguchi, Kenichi Eshima, Shinya Fujiki, Masashi Fujita, Shinya Hiramitsu, Satoshi HoshideAkihiko Hoshino, Yuki Ikeda, Yumi Ikehara, Takayuki Inomata, Teruo Inoue, Katsuhisa Ishii, Nobukazu Ishizaka, Masaaki Ito, Noriaki Iwahashi, Katsuomi Iwakura, Toshiaki Kadokami, Haruo Kamiya, Takahiro Kanbara, Yumiko Kanzaki, Ken Kashimura, Keisuke Kida, Kazuo Kimura, Satoru Kishi, Shuichi Kitada, Akihiro Kiyosue, Kazuhisa Kodama, Takayuki Kojima, Takumi Kondo, Yoshiaki Kubota, Kenya Kusunose, Noritaka Machii, Kazuo Matsunaga, Yasuto Matsuo, Yashushi Matsuzawa, Takeshi Mikami, Toru Minamino, Takahiro Nagai, Yasuko Nagano, Masashi Nagumo, Ikuko Nakamura, Katsunori Nakamura, Hiriyuki Naruse, Masami Nishino, Shinichi Niwano, Mitsutoshi Oguri, Nobuyuki Ohte, Masayoshi Oikawa, Takahiro Okumura, Masanori Okumura, Katsuya Onishi, Yukio Ozaki, Kan Saito, Tomohiro Sakamoto, Masashi Sakuma, Hisakuni Sekino, Kazuki Shiina, Michio Shimabukuro, Makoto Suzuki, Kunihiro Suzuki, Hiroyuki Takahama, Naohiko Takahashi, Yasuchika Takeishi, Shunsuke Tamaki, Akihiro Tanaka, Syuzo Tanimoto, Hiroki Teragawa, Tomoyuki Tobushi, Takafumi Toita, Kotaro Tokuda, Hirofumi Tomiyama, Hiroyuki Tsutsui, Hiroki Uehara, Masaaki Uematsu, Hirotaka Watada, Kazuyuki Yahagi, Takahisa Yamada, Hirotsugu Yamada, Tatsuya Yoshida, Akiomi Yoshihisa

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract:There were few clinical studies on the relationship between sodium glucose cotransporter 2 inhibitors (SGLT2i) and hematopoiesis in patients with diabetes (DM) and heart failure (HF) with consideration of systemic volume status. A total of 226 DM patients with HF enrolled in the CANDLE trial, a multicenter, prospective, randomized open-label blinded-endpoint trial, were studied. Estimated plasma volume status (ePVS) was calculated based on a weight-and hematocrit-based formula. At baseline, there was no significant difference in hematocrit and hemoglobin between the canagliflozin (n = 109) and glimepiride (n = 116) groups. Hematocrit and hemoglobin at 24 weeks, changes in hematocrit and hemoglobin difference (24 weeks-baseline), and hematocrit and hemoglobin ratio (24 weeks/baseline) were significantly higher in the canagliflozin than in the glimepiride group, respectively. There was no significant difference in ePVS at baseline and 24 weeks between the 2 groups. After adjustment for baseline parameters, canagliflozin correlated positively with changes in hematocrit and hemoglobin difference, and hematocrit and hemoglobin ratio by multivariate linear regression analyses. The difference in hematocrit and hemoglobin between the 2 groups became statistically significant at 3 and 6 months after randomization. There was no heterogeneity between canagliflozin and the characteristics of the patients for hematocrit and hemoglobin difference and ratio. A correlation of the changes in hematocrit and hemoglobin with cardiac and renal improvement was not observed. In conclusion, canagliflozin was associated with an increased hematocrit and hemoglobin in patients with diabetes and HF regardless of their volume status and characteristics.

Original languageEnglish
Pages (from-to)61-68
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume82
Issue number1
DOIs
Publication statusPublished - 19-07-2023

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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