Dapagliflozin reduced 24-h systolic blood pressure by 6.5 mmHg (95% CI -10.1 to -3.0, p<0.001) at Day 14 in patients with type 2 diabetes and/or CKD, without increasing sodium excretion.
Does dapagliflozin reduce blood pressure and increase sodium excretion in patients with type 2 diabetes and/or chronic kidney disease?
Dapagliflozin reduces blood pressure in patients with type 2 diabetes and/or chronic kidney disease without increasing sodium excretion, suggesting blood pressure-lowering effects occur through mechanisms beyond natriuresis.
Effect estimate: Mean reduction 6.5 mmHg (95% CI -10.1, -3.0)
p-value: p=< 0.001
AIMS: We assessed the effects of dapagliflozin on natriuresis and blood pressure in patients with type 2 diabetes and chronic kidney disease (CKD) and evaluated the consistency of these effects across patients with type 2 diabetes without CKD and CKD without type 2 diabetes. MATERIALS AND METHODS: We conducted a mechanistic, nonrandomised, open-label study to evaluate the effects of dapagliflozin on sodium excretion and blood pressure in patients with type 2 diabetes and CKD under a standardised sodium intake (150 mmol/day). Evaluations were performed at baseline (average of Days -3 to -1), treatment start (average of Days 2-4; hereafter referred to as Day 4), treatment end (average of Days 12-14; hereafter referred to as Day 14) and washout (average of Days 15-17). Similar protocols were applied to the type 2 diabetes without CKD and CKD without type 2 diabetes strata. Data from all strata were pooled to assess the consistency of the effects of dapagliflozin. RESULTS: In 13 participants with type 2 diabetes and CKD, 24-h sodium excretion did not increase during treatment, as reflected by changes from baseline (Day 4 change: -0.5 mmol/24-h 95% CI -15.4, 14.5, p = 0.95; Day 14 change: -11.7 mmol/24-h 95% CI -30.4, 7.1). Compared to baseline, 24-h systolic blood pressure decreased by 6.0 mmHg 95% CI -19.8, 7.7 at Day 4 and by 3.7 mmHg 95% CI -13.7, 6.2 at Day 14. In the pooled stratum of 33 participants, 24-h sodium excretion remained unchanged relative to baseline (Day 4 change: -7.4 mmol/24-h 95% CI -16.2, 1.5, p = 0.10; Day 14 change: -10.1 mmol/24-h 95% CI -25.1, 5.0, p = 0.18), whereas 24-h systolic blood pressure was consistently reduced by 6.8 mmHg (95% CI -10.4, -3.3, p < 0.001) at Day 4 and by 6.5 mmHg (95% CI -10.1, -3.0, p < 0.001) at Day 14, with no evidence of heterogeneity across strata. CONCLUSIONS: Dapagliflozin reduced blood pressure during standardised sodium intake in patients with type 2 diabetes and/or CKD without increasing sodium excretion, suggesting that the blood pressure-lowering effects occur through mechanisms beyond natriuresis.
Beernink et al. (Fri,) conducted a other in Type 2 diabetes and/or chronic kidney disease (n=33). Dapagliflozin vs. Baseline was evaluated on Change in 24-h systolic blood pressure at Day 14 (Mean reduction 6.5 mmHg, 95% CI -10.1, -3.0, p=< 0.001). Dapagliflozin reduced 24-h systolic blood pressure by 6.5 mmHg (95% CI -10.1 to -3.0, p<0.001) at Day 14 in patients with type 2 diabetes and/or CKD, without increasing sodium excretion.