Biomarkers for arteriosclerosis
ABI
The common mean-IMT-CCA, right max-IMT-CCA, and left max-IMT-CCA at baseline in the tofogliflozin conventional treatment groups are shown in Table Effects of tofogliflozin on biomarkers of arteriosclerosis0.873 ± 0.156(n = 146)0.870 ± 0.159(n = 145)0.738 ± 0.145(n = 145)− 0.135 (0.007)(p < 0.001)0.724 ± 0.136(n = 143)− 0.145 (0.007)(p < 0.001)0.010 (− 0.010, 0.030)(p = 0.32)0.807 ± 0.149(n = 137)− 0.067 (0.009)(p < 0.001)0.790 ± 0.141(n = 129)− 0.080 (0.009)(p < 0.001)0.013 (− 0.012, 0.037)(p = 0.32)1.064 ± 0.300(n = 146)1.069 ± 0.263(n = 144)0.911 ± 0.305(n = 145)− 0.154 (0.013)(p < 0.001)0.879 ± 0.218(n = 142)− 0.188 (0.013)(p < 0.001)0.034 (− 0.002, 0.069)(p = 0.06)1.031 ± 0.369(n = 137)− 0.040 (0.023)(p = 0.09)1.012 ± 0.338(n = 129)− 0.052 (0.024)(p = 0.031)0.012 (− 0.053, 0.078)(p = 0.72)1.148 ± 0.383(n = 146)1.127 ± 0.384(n = 144)0.965 ± 0.391(n = 145)− 0.185 (0.021)(p < 0.001)0.929 ± 0.313(n = 142)− 0.196 (0.021)(p < 0.001)0.012 (− 0.048, 0.071)(p = 0.70)1.099 ± 0.413(n = 137)− 0.053 (0.029)(p = 0.07)1.096 ± 0.503(n = 129)− 0.048 (0.029)(p = 0.10)− 0.005 (− 0.086, 0.076)(p = 0.91)1706.2 ± 419.5(n = 75)1655.2 ± 319.5(n = 65)1685.5 ± 352.3(n = 72)− 54.5 ± 235.9(p = 0.06)1738.6 ± 362.2(n = 63)56.5 ± 199.1(p = 0.033)− 111.0 (− 188.6, − 33.5)(p = 0.005)1689.6 ± 391.2(n = 65)− 17.5 ± 221.3(p = 0.54)1774.4 ± 329.4(n = 53)82.7 ± 210.3(p = 0.008)− 100.2 (− 182.8, − 17.5)(p = 0.018)1.13 ± 0.10(n = 104)1.14 ± 0.08(n = 95)1.14 ± 0.08(n = 97)0.01 ± 0.09(p = 0.30)1.15 ± 0.08(n = 88)0.00 ± 0.08(p = 0.98)0.01 (− 0.02, 0.04)(p = 0.47)1.15 ± 0.09(n = 88)0.01 ± 0.09(p = 0.17)1.14 ± 0.10(n = 73)0.00 ± 0.09(p = 0.68)0.02 (− 0.01, 0.05)(p = 0.22)Data are presented as the mean ± standard deviation or adjusted mean change (standard error). Comparisons of the IMT-CCA, baPWV, and ABI values during treatment with those at baseline were performed using a one-sample t-test based on the mixed-effects model for repeated measures. Intergroup differences in IMT-CCA measurements were analyzed using Student’s t-test. Intergroup differences in changes in IMT-CCA from baseline (treatment effect) were analyzed using the mixed-effects model for repeated measures. The treatment group, week, interactions between treatment group and week, age, sex, use of insulin at baseline, and baseline IMT-CCA were included as fixed effects. IMT-CCA: intima-media thickness of the common carotid artery; baPWV: brachial-ankle pulse wave velocity; ABI: ankle-brachial index; 95% CI: 95% confidence intervalDuring the main UTOPIA study (from baseline to week 104), the common mean-IMT-CCA and right and left max-IMT-CCA significantly decreased in both the tofogliflozin and conventional treatment groups, although no significant intergroup differences in the changes were observed in a mixed-effects model for repeated measures. The common mean-IMT-CCA showed a significant reduction throughout the follow-up period (from baseline to the end of the UTOPIA Extension study in both groups (week 208)); however, no significant intergroup differences in the changes were observed (Table The mean baPWV significantly increased in the conventional treatment group throughout the follow-up period and was maintained or even decreased in the tofogliflozin group, resulting in a significant intergroup difference in the changes throughout the follow-up period (Table The ABI did not change significantly throughout the follow-up period in either group. When the ABI was classified into three categories (abnormally low (ABI ≤ 0.9), within the normal range (0.9 < ABI < 1.3), and abnormally high (1.3 ≤ ABI)), the proportion of patients whose ABI was within the normal range was as high as more than 95% at baseline, and no significant intergroup differences were observed throughout the follow-up period (Additional file 