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Updated: Mar 6, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal Function
Sergei Petrykiv1, C David Sjöström2, Peter J Greasley2
1Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Insights
Dapagliflozin effectively lowers HbA1c, body weight, blood pressure, and albuminuria in type 2 diabetes patients. Its glucose-lowering effect diminishes with reduced kidney function, but other benefits remain consistent across eGFR levels.
Area of Science:
- Cardiology
- Endocrinology
- Nephrology
Background:
- Sodium glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin reduce HbA1c, weight, blood pressure, and albuminuria.
- Dapagliflozin increases hematocrit, potentially via osmotic diuresis.
- Previous studies indicate reduced HbA1c-lowering efficacy of dapagliflozin at lower estimated glomerular filtration rates (eGFR).
Purpose of the Study:
- To evaluate the impact of dapagliflozin on cardiovascular risk factors across different baseline eGFR levels.
- To assess whether the effects of dapagliflozin on HbA1c, body weight, blood pressure, hematocrit, and albuminuria are consistent across varying degrees of renal function.
Main Methods:
- A pooled analysis of 11 phase 3 clinical trials involving patients with type 2 diabetes.
- Patients received either placebo (n=2178) or dapagliflozin 10 mg (n=2226) for 24 weeks.
- Outcomes were analyzed based on baseline eGFR categories: ≥45 to <60, ≥60 to <90, and ≥90 ml/min per 1.73 m².
Main Results:
- HbA1c reductions with dapagliflozin decreased progressively with lower eGFR (0.6% to 0.3%, P<0.001).
- Dapagliflozin's effects on hematocrit, body weight, and blood pressure were consistent across all eGFR subgroups.
- Greater reductions in albuminuria were observed in the lowest eGFR subgroup among patients with baseline albuminuria ≥30 mg/g (P<0.001).
Conclusions:
- The glucose-lowering effect of dapagliflozin diminishes as kidney function declines.
- Dapagliflozin consistently reduces body weight, blood pressure, and albuminuria irrespective of baseline eGFR.
- Consistent effects on hematocrit suggest dapagliflozin's benefits may involve non-glucose-dependent mechanisms, potentially related to volume contraction.
Background And Objective:
Sodium glucose cotransporter 2 inhibition with dapagliflozin decreases hemoglobin A1c (HbA1c), body weight, BP, and albuminuria (urinary albumin-to-creatinine ratio). Dapagliflozin also modestly increases hematocrit, likely related to osmotic diuresis/natriuresis. Prior studies suggest that the HbA1c-lowering effects of dapagliflozin attenuate at lower eGFR. However, effects on other cardiovascular risk factors at different eGFR levels are incompletely understood.
Design, Setting, Participants, & Measurements:
This pooled analysis of 11 phase 3 clinical trials assessed changes in HbA1c, body weight, BP, hematocrit, and urinary albumin-to-creatinine ratio with placebo (n=2178) or dapagliflozin 10 mg (n=2226) over 24 weeks in patients with type 2 diabetes according to baseline eGFR (eGFR≥45 to <60 ml/min per 1.73 m2, eGFR≥60 to <90 ml/min per 1.73 m2, and eGFR≥90 ml/min per 1.73 m2).
Results:
Compared with placebo, reductions in HbA1c with dapagliflozin were 0.6%, 0.5%, and 0.3%, respectively, for each consecutive lower eGFR subgroup (P value interaction <0.001). Effects of dapagliflozin on hematocrit, body weight, and BP were similar regardless of baseline eGFR, suggesting that effects potentially related to volume and natriuresis are eGFR independent. Moreover, among individuals with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, placebo-adjusted reductions in urinary albumin-to-creatinine ratio were larger in the lowest eGFR subgroup (P value interaction <0.001). Adverse events occurred more frequently in the lowest eGFR subgroup; this was true for both dapagliflozin- and placebo-treated patients.
Conclusions:
The HbA1c-lowering effects of dapagliflozin decrease as renal function declines. However, dapagliflozin consistently decreases body weight, BP, and urinary albumin-to-creatinine ratio regardless of eGFR. These effects in conjunction with the finding of similar effects on hematocrit, a proxy for volume contraction, suggest that the effects of dapagliflozin are partly mediated via nonglucosuric-dependent mechanisms.
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