Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial
Abstract Background This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. Methods This...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-06-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-01879-4 |
| _version_ | 1797795856425943040 |
|---|---|
| author | Naoto Katakami Tomoya Mita Hidenori Yoshii Toshihiko Shiraiwa Tetsuyuki Yasuda Yosuke Okada Akira Kurozumi Masahiro Hatazaki Hideaki Kaneto Takeshi Osonoi Tsunehiko Yamamoto Nobuichi Kuribayashi Kazuhisa Maeda Hiroki Yokoyama Keisuke Kosugi Kentaro Ohtoshi Isao Hayashi Satoru Sumitani Mamiko Tsugawa Kayoko Ryomoto Ken Kato Tadashi Nakamura Satoshi Kawashima Yasunori Sato Hirotaka Watada Iichiro Shimomura the UTOPIA study investigators |
| author_facet | Naoto Katakami Tomoya Mita Hidenori Yoshii Toshihiko Shiraiwa Tetsuyuki Yasuda Yosuke Okada Akira Kurozumi Masahiro Hatazaki Hideaki Kaneto Takeshi Osonoi Tsunehiko Yamamoto Nobuichi Kuribayashi Kazuhisa Maeda Hiroki Yokoyama Keisuke Kosugi Kentaro Ohtoshi Isao Hayashi Satoru Sumitani Mamiko Tsugawa Kayoko Ryomoto Ken Kato Tadashi Nakamura Satoshi Kawashima Yasunori Sato Hirotaka Watada Iichiro Shimomura the UTOPIA study investigators |
| author_sort | Naoto Katakami |
| collection | DOAJ |
| description | Abstract Background This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. Methods This was a prospective observational 2-year extension study of the “Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)” trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. Results The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (− 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (− 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) − 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (− 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (− 100.2 cm/s, 95% CI − 182.8 to − 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. Conclusions Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile. |
| first_indexed | 2024-03-13T03:24:19Z |
| format | Article |
| id | doaj.art-8358aaeab0374c86b4c5f65e4528a3a5 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-13T03:24:19Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-8358aaeab0374c86b4c5f65e4528a3a52023-06-25T11:08:10ZengBMCCardiovascular Diabetology1475-28402023-06-0122111510.1186/s12933-023-01879-4Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trialNaoto Katakami0Tomoya Mita1Hidenori Yoshii2Toshihiko Shiraiwa3Tetsuyuki Yasuda4Yosuke Okada5Akira Kurozumi6Masahiro Hatazaki7Hideaki Kaneto8Takeshi Osonoi9Tsunehiko Yamamoto10Nobuichi Kuribayashi11Kazuhisa Maeda12Hiroki Yokoyama13Keisuke Kosugi14Kentaro Ohtoshi15Isao Hayashi16Satoru Sumitani17Mamiko Tsugawa18Kayoko Ryomoto19Ken Kato20Tadashi Nakamura21Satoshi Kawashima22Yasunori Sato23Hirotaka Watada24Iichiro Shimomura25the UTOPIA study investigatorsDepartment of Metabolic Medicine, Osaka University Graduate School of MedicineDepartment of Metabolism & Endocrinology, Juntendo University Graduate School of MedicineDepartment of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical CenterShiraiwa Medical ClinicDepartment of Endocrinology and Metabolism, Osaka Police HospitalFirst Department of Internal Medicine, School of Medicine, University of Occupational and Environmental HealthFirst Department of Internal Medicine, School of Medicine, University of Occupational and Environmental HealthDepartment of Diabetes and Endocrinology, Osaka General Medical CenterDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolNakakinen ClinicDiabetes and Endocrinology, Kansai Rosai HospitalMisaki Naika ClinicKitasenri Maeda ClinicJiyugaoka Medical ClinicKosugi Medical ClinicOtoshi Medical ClinicHayashi ClinicCenter for Diabetes and Endocrinology, Nippon Life HospitalDepartment of Endocrinology and Metabolism, Ikeda Municipal HospitalCenter for Diabetes Mellitus, Osaka Rosai HospitalDiabetes Center, National Hospital Organization Osaka National HospitalDepartment of Internal Medicine, Kawasaki HospitalKanda Naika ClinicDepartment of Preventive Medicine and Public Health, Keio University School of MedicineDepartment of Metabolism & Endocrinology, Juntendo University Graduate School of MedicineDepartment of Metabolic Medicine, Osaka University Graduate School of MedicineAbstract Background This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. Methods This was a prospective observational 2-year extension study of the “Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)” trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. Results The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (− 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (− 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) − 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (− 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (− 100.2 cm/s, 95% CI − 182.8 to − 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. Conclusions Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.https://doi.org/10.1186/s12933-023-01879-4AtherosclerosisBrachial-ankle pulse wave velocityCardiovascular risk factorsCarotid intima-media thicknessSodium-glucose cotransporter 2 inhibitorTofogliflozin |
| spellingShingle | Naoto Katakami Tomoya Mita Hidenori Yoshii Toshihiko Shiraiwa Tetsuyuki Yasuda Yosuke Okada Akira Kurozumi Masahiro Hatazaki Hideaki Kaneto Takeshi Osonoi Tsunehiko Yamamoto Nobuichi Kuribayashi Kazuhisa Maeda Hiroki Yokoyama Keisuke Kosugi Kentaro Ohtoshi Isao Hayashi Satoru Sumitani Mamiko Tsugawa Kayoko Ryomoto Ken Kato Tadashi Nakamura Satoshi Kawashima Yasunori Sato Hirotaka Watada Iichiro Shimomura the UTOPIA study investigators Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial Cardiovascular Diabetology Atherosclerosis Brachial-ankle pulse wave velocity Cardiovascular risk factors Carotid intima-media thickness Sodium-glucose cotransporter 2 inhibitor Tofogliflozin |
| title | Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial |
| title_full | Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial |
| title_fullStr | Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial |
| title_full_unstemmed | Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial |
| title_short | Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial |
| title_sort | tofogliflozin long term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease a 2 year extension study of the utopia trial |
| topic | Atherosclerosis Brachial-ankle pulse wave velocity Cardiovascular risk factors Carotid intima-media thickness Sodium-glucose cotransporter 2 inhibitor Tofogliflozin |
| url | https://doi.org/10.1186/s12933-023-01879-4 |
| work_keys_str_mv | AT naotokatakami tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT tomoyamita tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT hidenoriyoshii tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT toshihikoshiraiwa tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT tetsuyukiyasuda tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT yosukeokada tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT akirakurozumi tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT masahirohatazaki tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT hideakikaneto tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT takeshiosonoi tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT tsunehikoyamamoto tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT nobuichikuribayashi tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT kazuhisamaeda tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT hirokiyokoyama tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT keisukekosugi tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT kentaroohtoshi tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT isaohayashi tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT satorusumitani tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT mamikotsugawa tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT kayokoryomoto tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT kenkato tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT tadashinakamura tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT satoshikawashima tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT yasunorisato tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT hirotakawatada tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT iichiroshimomura tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial AT theutopiastudyinvestigators tofogliflozinlongtermeffectsonatherosclerosisprogressionandmajorclinicalparametersinpatientswithtype2diabetesmellituslackingahistoryofcardiovasculardiseasea2yearextensionstudyoftheutopiatrial |