Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal Function

Clinical journal of the American Society of Nephrology: CJASN

Sergei Petrykiv² 

[1] and..§Steno Diabetes Center, Gentofte, Denmark..*Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;*Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;†AstraZeneca Gothenburg, Mölndal, Sweden;‡AstraZeneca, Gaithersburg, Maryland

关键词: albuminuria;    cardiovascular;    diabetic nephropathy;    Benzhydryl Compounds;    blood pressure;    Body Weight;    Cardiovascular Diseases;    Diabetes Mellitus, Type 2;    glomerular filtration rate;    Glucosides;    Hematocrit;    Humans;    Hypoglycemic Agents;    Natriuresis;    risk factors;   

DOI  :  10.2215/CJN.10180916

学科分类：泌尿医学

来源: American Society of Nephrology

【 摘 要 】

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.

【 授权许可】

CC BY