Table 2.
LS Mean and Placebo‐Subtracted LS Mean Change From Baseline to Week 6 (Last Observation Carried Forward)
| Endpoint | Canagliflozin 300 mg (n=56) | Canagliflozin 100 mg (n=57) | Placebo (n=56) | ||
|---|---|---|---|---|---|
| P Value (Minus Placebo)a | P Valuea | ||||
| Mean 24‐hour ABPM SBP change, mm Hg | |||||
| LS mean (SE) | −6.2 (1.4) | −4.5 (1.4) | −1.2 (1.4) | ||
| PBO‐subtracted LS mean (95% CI) | −4.9 (−8.4 to −1.5) | .006 b | −3.3 (−6.7 to 0.2) | .062 | |
| LS mean (SE)b | −6.6 (1.4) | −5.0 (1.4) | −1.4 (1.5) | ||
| PBO‐subtracted LS mean (95% CI)b | −5.2 (−8.9 to −1.6) | .006 | −3.77 (−7.4 to −0.0c) | .049 | |
| Mean 24‐hour ABPM DBP change, mm Hg | |||||
| LS mean (SE) | −3.2 (0.8) | −2.2 (0.8) | −0.3 (0.8) | ||
| PBO‐subtracted LS mean (95% CI) | −2.9 (−5.0 to −0.9) | .005 | −1.9 (−4.0 to 0.1) | .062 | |
| LS mean (SE)b | −3.4 (0.8) | −2.3 (0.8) | −0.4 (0.9) | ||
| PBO‐subtracted LS mean (95% CI)b | −3.0 (−5.2 to −0.9) | .006 | −2.0 (−4.1 to 0.2) | .071 | |
| Mean daytime ABPM SBP change, mm Hg | |||||
| LS mean (SE) | −6.2 (1.4) | −4.8 (1.4) | −0.8 (1.4) | ||
| PBO‐subtracted LS mean (95% CI) | −5.4 (−8.9 to −1.9) | .003 | −4.0 (−7.5 to −0.5) | .025 | |
| Mean daytime ABPM DBP change, mm Hg | |||||
| LS mean (SE) | −3.1 (0.8) | −2.4 (0.8) | −0.2 (0.8) | ||
| PBO‐subtracted LS mean (95% CI) | −3.0 (−5.0 to −0.9) | .006 | −2.2 (−4.3 to −0.1) | .039 | |
| Mean nighttime ABPM SBP change, mm Hg | |||||
| LS mean (SE) | −6.2 (1.7) | −4.0 (1.6) | −3.2 (1.7) | ||
| PBO‐subtracted LS mean (95% CI) | −3.0 (−7.2 to 1.1) | .152 | −0.9 (−5.1 to 3.3) | .676 | |
| Mean nighttime ABPM DBP change, mm Hg | |||||
| LS mean (SE) | −3.6 (1.0) | −2.0 (1.0) | −1.2 (1.0) | ||
| PBO‐subtracted LS mean (95% CI) | −2.4 (−4.9 to 0.2) | .071 | −0.8 (−3.4 to 1.8) | .557 | |
| Seated office SBP, mm Hg | |||||
| LS mean (SE) | −7.5 (2.0) | −5.3 (2.0) | −3.9 (2.0) | ||
| PBO‐subtracted LS mean (95% CI) | −3.6 (−8.7 to 1.6) | .173 | −1.3 (−6.4 to 3.8) | .604 | |
| Seated office DBP, mm Hg | |||||
| LS mean (SE) | −2.8 (1.1) | −2.1 (1.1) | −2.2 (1.1) | ||
| PBO‐subtracted LS mean (95% CI) | −0.6 (−3.4 to 2.2) | .688 | 0.2 (−2.6 to 3.0) | .898 | |
| FPG change, mmol/L | |||||
| LS mean (SE) | −1.6 (0.3) | −0.2 (0.3) | −0.4 (0.3) | ||
| PBO‐subtracted LS mean (95% CI) | −1.2 (−2.0 to −0.3) | .009 | 0.2 (−0.7 to 1.1) | .636 | |
| Body weight change, % | |||||
| LS mean (SE) | −1.5 (0.4) | −1.1 (0.4) | 0.2 (0.4) | ||
| PBO‐subtracted LS mean (95% CI) | −1.7 (−2.7 to −0.7) | <.001 | −1.3 (−2.3 to −0.4) | .008 | |
Abbreviations: ABPM, ambulatory blood pressure monitoring; ANCOVA, analysis of covariance; CI, confidence interval; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; LS, least squares; PBO, placebo; SBP, systolic blood pressure; SE, standard error. Note: The LS mean is presented with associated P values and 95% CI based on ANCOVA models with terms for treatment, the use of β‐blockers at baseline strata as factors, and adjusting for the baseline value as a covariate. Based on the prespecified hierarchical testing sequence (which included testing the mean 24‐hour ambulatory SBP, mean 24‐hour ambulatory DBP, FPG, body weight, and mean daytime and mean nighttime SBP and DBP), the change from baseline in the mean 24‐hour ambulatory SBP for canagliflozin 100 mg was compared with the PBO group following the statistically significant comparison of canagliflozin 300 mg vs PBO. Although the canagliflozin 100‐mg dose showed greater numerical reductions in the mean 24‐hour ambulatory SBP compared with PBO, it did not achieve statistical significance. Due to the lack of statistical significance for this comparison, P values reported for subsequent endpoints are considered to be strictly nominal with no inference regarding their statistical significance. aNominal P value. bCompleter analysis set: canagliflozin 300 mg (n=54), canagliflozin 100 mg (n=54), placebo (n=47). cValue: −.003. The bold value indicates statistical significance.