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Clinical Trial
. 2016 Jun;18(6):590-7.
doi: 10.1111/dom.12654.

Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

H J L Heerspink  1 , E Johnsson  2 , I Gause-Nilsson  2 , V A Cain  3 , C D Sjöström  2
Affiliations
Clinical Trial

Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

H J L Heerspink et al. Diabetes Obes Metab. 2016 Jun.

Abstract

Aims: To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR.

Methods: We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline.

Results: Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12-week reductions in albuminuria compared with placebo: -33.2% [95% confidence interval (CI) -45.4, -18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: -23.5% (95% CI -37.6, -6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal-related adverse events were observed in any group.

Conclusions: Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin-angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin-induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long-term renal and cardiovascular risk.

Keywords: albuminuria; dapagliflozin; diabetes; hypertension; sodium glucose cotransporter-2.

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Figures

Figure 1
Figure 1
Change in (A) urine albumin/creatinine ratio (UACR) and (B) estimated glomerular filtration rate (eGFR) over time. Error bars represent 95% confidence interval (CI). ACE, angiotensin‐converting enzyme; ARB, angiotensin receptor blocker; DAPA, dapagliflozin; PBO, placebo.
Figure 2
Figure 2
(A) Effect of dapagliflozin versus placebo on glycated haemoglobin (HbA1c) and effect of dapagliflozin on urine albumin/creatinine ratio (UACR) stratified by HbA1c response. (B) Effect of dapagliflozin versus placebo on systolic blood pressure (SBP) and effect of dapagliflozin on UACR stratified by SBP response.
Figure 3
Figure 3
Effect of dapagliflozin versus placebo on albuminuria and proportion of effect mediated by changes in glycated haemoglobin (HbA1c), systolic blood pressure (SBP), body weight (BW) and estimated glomerular filtration rate (eGFR).
See this image and copyright information in PMC

References

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