Overall Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Versus Dipeptidyl-Peptidase 4 Inhibitors: Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT study)

Masahiro Sugawara; Masahiro Fukuda; Ichiro Sakuma; Yutaka Wakasa; Hideaki Funayama; Akira Kondo; Naoki Itabashi; Yasuyuki Maruyama; Takashi Kamiyama; Yasunori Utsunomiya; Akira Yamauchi; Hidenori Yoshii; Hirokazu Yamada; Koichi Mochizuki; J-SELECT study investigators

doi:10.1007/s13300-023-01438-w

Overall Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Versus Dipeptidyl-Peptidase 4 Inhibitors: Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT study)

Diabetes Ther. 2023 Sep;14(9):1517-1535. doi: 10.1007/s13300-023-01438-w. Epub 2023 Jul 6.

Authors

Collaborators

J-SELECT study investigators:
Hiroaki Seino, Kaori Murata, Shigeo Yatagai, Hiroshi Koyama, Hareaki Yamamoto, Miho Shimizu, Toshio Kawada, Setsuya Sakagashira, Shigehiko Ozeki, Tomoo Takeda, Tomohiro Katsuya, Mariko Oishi, Ken-Ich Doniwa, Nobuyuki Ueda, Makiko Sasamoto, Hatsumi Masaki, Takashi Kamiyama, Woon-Joo Lee, Hiroko Chimori, Hiroshi Takeda, Kazuo Ikeda, Hiroaki Nishioka, Kyoko Mitsuhashi, Toru Kinugawa, Motoko Miki, Toshiyuki Horiuchi, Kunihiro Doi, Yuki Shinagawa, Isato Shimozono, Jinro Ishizuka, Shunichiro Sakurai, Shigeki Moritani, Norio Kase, Shigeru Watanabe, Shinsuke Nakata, Keiko Tsunoda, Tadashi Sawanishi, Yuji Ogawa, Tomokazu Matsuda, Tomohiro Tsuji, Shinichiro Shirabe, Satoshi Ashitomi, Hiromi Ogata, Kaneyuki Matsuo, Takashi Sugie, Ken Takenaka, Asami Tanaka, Yoshiro Suzuki, Masahiro Inoue, Hiroshi Hasegawa, Haruyoshi Nakao, Tetsuo Nishikawa, Mikio Uematsu, Daigaku Uchida, Masaaki Miyakawa, Masahiro Takihata, Hirotaka Ishii, Kenji Mizuno, Masahiko Inomata, Kosuke Minamisawa, Soichi Honda, Mitsuo Shirakawa, Katsuya Fuse, Takuji Yamao, Akihiko Nakazima, Masahiro Nagano, Masahiko Nakamura, Suzuko Iwami, Hisakazu Degawa, Naoko Katayanagi, Yoshiharu Okada, Hideaki Sawaki, Hiromi Ogata, Motoshige Miyano, Yuki Matsuda

Affiliations

¹ Sugawara Clinic, 3-9-16 Syakujii-machi, Nerima, Tokyo, 177-0041, Japan. ms@sugawara.or.jp.
² Fukuda Clinic, 1-6-1, Miyahara, Yodogawa, Osaka-shi, Osaka, 532-0003, Japan.
³ Caress Sapporo Hokko Memorial Clinic, Kita-17, Higashi-8, 1-15, Sapporo, Hokkaido, 065-0027, Japan.
⁴ Wakasa Medical Clinic, 3-16-25, Sainen, Kanazawa, Ishikawa, 920-0024, Japan.
⁵ Funayama Medical Clinic, 1-13-14 Tomioka, Koto, Tokyo, 135-0047, Japan.
⁶ Kondo Hospital, 1-6-25 Nishi-Shinhama-cho, Tokushima, 770-8008, Japan.
⁷ Itabashi Clinic, 815-1, Higashi-Ushigaya, Koga, Ibaraki, 306-0232, Japan.
⁸ Iwatsuki-Minami Hospital, 2256 Kuroya Iwatsuki, Saitama-shi, Saitama, 339-0033, Japan.
⁹ Kamiyama Clinic, 5-21-18, Takanodai, Nerima, Tokyo, 177-0033, Japan.
¹⁰ Hoya Hospital, 4-50-15 Minami-Oizumi, Nerima, Tokyo, 178-0064, Japan.
¹¹ Suruga Clinic, 9-23, Shoufuku-cho, Shimizu, Shizuoka, Shizuoka, 424-0855, Japan.
¹² Department of Diabetes and Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, 3-3-20 Shinsuna, Koto, Tokyo, 136-0075, Japan.
¹³ Soiken Inc., Chiyoda, Tokyo, 101-0052, Japan.
¹⁴ Mochizuki Naika Clinic, 4-5, Aioi-cho, Itabashi, Tokyo, 174-0044, Japan.

Abstract

Introduction: Evidence of a direct comparison between dipeptidyl-peptidase 4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) remains lacking, and no clear treatment strategy or rationale has been established using these drugs. This study aimed to compare the overall efficacy and safety of DPP-4is and the SGLT2i luseogliflozin in patients with type 2 diabetes mellitus (T2DM).

Methods: Patients with T2DM who had not used antidiabetic agents or who had used antidiabetic agents other than SGLT2is and DPP-4is were enrolled in the study after written informed consent had been obtained. The enrolled patients were subsequently randomly assigned to either the luseogliflozin or DPP-4i group and followed up for 52 weeks. The primary (composite) endpoint was the proportion of patients who showed improvement in ≥ 3 endpoints among the following five endpoints from baseline to week 52: glycated hemoglobin (HbA1c), weight, estimated glomerular filtration rate (eGFR), systolic blood pressure, and pulse rate.

Results: A total of 623 patients were enrolled in the study and subsequently randomized to either the luseogliflozin or DPP-4i groups. The proportion of patients who showed improvement in ≥ 3 endpoints at week 52 was significantly higher in the luseogliflozin group (58.9%) than in the DPP-4i group (35.0%) (p < 0.001). When stratified by body mass index (BMI) (< 25 or ≥ 25 kg/m²) or age (< 65 or ≥ 65 years), regardless of BMI or age, the proportion of patients who achieved the composite endpoint was significantly higher in the luseogliflozin group than in the DPP-4i group. Hepatic function and high-density lipoprotein-cholesterol were also significantly improved in the luseogliflozin group compared with the DPP-4i group. The frequency of non-serious/serious adverse events did not differ between the groups.

Conclusion: This study showed the overall efficacy of luseogliflozin compared with DPP-4is over the mid/long term, regardless of BMI or age. The results suggest the importance of assessing multiple aspects regarding the effects of diabetes management.

Trial registration number: jRCTs031180241.

Keywords: Composite endpoint; Dipeptidyl-peptidase 4 inhibitor; Estimated glomerular filtration rate; Glycated hemoglobin; Luseogliflozin; Overall efficacy; Pulse rate; Sodium-glucose cotransporter 2 inhibitor; Systolic blood pressure; Weight.