Dapagliflozin does not impair microvascular hemorheology in type 2 diabetes mellitus: A multicenter randomized controlled trial (D‐ PATH study)

Figures

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  Figure 1. Patient allocation flowchart. Flowchart illustrating patient enrollment and allocation. A total of 90 patients were randomized to the dapagliflozin group (n = 45) or the control group (n = 45). In the dapagliflozin group, one patient withdrew consent and two were excluded due to inappropriate measurement, resulting in 42 patients in the full analysis set (FAS). In the control group, three patients withdrew consent, and two were excluded for similar reasons, resulting in 40 patients in the FAS. After further exclusions for protocol deviation (one in the dapagliflozin group and two in the control group), 41 patients in the dapagliflozin group and 38 in the control group were included in the per‐protocol set (PPS).

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  Figure 2. Noninferiority assessment of changes in whole blood passage time from baseline to 16 weeks by baseline whole blood passage time. Subgroup analysis stratified by baseline whole blood passage time (WBPT; above vs below the median) and baseline HbA1c (>8.0% vs ≤8.0%). Data are presented as mean differences (dapagliflozin—control) with 95% confidence intervals (CI). The prespecified noninferiority margin (+6 s) is shown as a dashed line. Noninferiority was concluded if the upper limit of the two‐sided 95% CI was <6 s. In participants with a baseline transit time above the median (n = 37), the between‐group difference (dapagliflozin—control) was 0.8 s (95% CI, −2.0 to 3.7, P = 0.534), with mean changes of −0.6 s (95% CI, −2.4 to 1.1) in the dapagliflozin group (n = 18) and −1.4 s (95% CI, −3.5 to 0.7) in the control group (n = 19). In participants with a baseline transit time below the median (n = 45), the between‐group difference was 3.0 s (95% CI, 0.5–5.3, P = 0.017), with mean changes of 3.0 s (95% CI, 0.9–5.0) in the dapagliflozin group (n = 24) and 0.0 s (95% CI, −1.3 to 1.3) in the control group (n = 21). In both subgroups, the upper limit of the two‐sided 95% CI was <6 s,…

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  Figure 3. Changes in hematocrit at 16 weeks by baseline hematocrit quartile. Mean change in hematocrit from baseline to 16 weeks in the dapagliflozin and control groups, stratified by baseline hematocrit quartiles: Q1 (<39.5%), Q2 (39.5–41.9%), Q3 (42.0–45.4%), and Q4 (≥45.5%). Data are presented as mean ± SD. In the dapagliflozin group, hematocrit increased consistently in Q1–Q3 (Panels a–c) compared with the control group, whereas no significant changes were observed in Q4 in either group (panel d). All subgroup analyses were exploratory. P values were not adjusted for multiplicity. SD, standard deviation.

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  Figure 4. Changes in erythropoietin levels by hematocrit quartile. Change from baseline to 16 weeks in serum erythropoietin levels (mean ± SD) in both treatment groups, stratified by hematocrit quartiles: Q1 (<39.5%), Q2 (39.5–41.9%), Q3 (42.0–45.4%), and Q4 (≥45.5%). Comparisons between groups were performed within each quartile. In Q1 (Panel a), the increase in serum erythropoietin levels was significantly greater in the dapagliflozin group than in the control group (P = 0.035). In contrast, no statistically significant between‐group differences were observed in Q2–Q4 (Panels b–d). Data are shown as mean ± SD. All subgroup analyses were exploratory. P values were not adjusted for multiplicity. SD, standard deviation.