Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective,
Naoto Katakami1,2, Tomoya Mita3, Hidenori Yoshii4
1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. katakami@endmet.med.osaka-u.ac.jp.
Background:
This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT).
Methods:
This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period.
Results:
In a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (- 0.132 mm, SE 0.007; - 0.163 mm, SE 0.013; - 0.170 mm, SE 0.020, respectively) and the control group (- 0.140 mm, SE 0.006; - 0.190 mm, SE 0.012; - 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (- 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (- 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (- 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups.
Conclusions/Interpretation:
No IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population. Clinical Trial Registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).
Insights
Tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, did not significantly alter atherosclerosis progression in type 2 diabetes patients. However, it effectively managed cardiovascular risk factors and was well-tolerated.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Atherosclerosis is a major concern in type 2 diabetes mellitus (T2DM).
- Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors are used to manage T2DM.
- Preventive effects of SGLT2 inhibitors on atherosclerosis progression in T2DM patients without cardiovascular disease (CVD) require investigation.
Purpose of the Study:
- To investigate the preventive effects of tofogliflozin on atherosclerosis progression.
- To monitor changes in carotid intima-media thickness (IMT) in T2DM patients without apparent CVD.
- To evaluate tofogliflozin's impact on cardiovascular risk factors.
Main Methods:
- Prospective, randomized, open-label, blinded-endpoint, multicenter study.
- 340 T2DM patients without apparent CVD were randomized into tofogliflozin or conventional treatment groups.
- Carotid intima-media thickness (IMT) was measured over 104 weeks.
Main Results:
- Both tofogliflozin and conventional treatment groups showed significant declines in mean and maximum carotid IMT.
- No significant difference in IMT progression was observed between the tofogliflozin and conventional treatment groups.
- Tofogliflozin significantly improved glycemic control (HbA1c, blood glucose), body weight, abdominal circumference, systolic blood pressure, and HDL-C levels.
Conclusions:
- Tofogliflozin did not significantly alter atherosclerosis progression as measured by IMT changes.
- Tofogliflozin demonstrated safety and efficacy in managing primary cardiovascular risk factors in T2DM patients.
- Tofogliflozin represents a viable treatment option for T2DM patients, particularly for managing associated metabolic and hemodynamic risk factors.
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