Does Renal Function Influence Effectiveness of Dapagliflozin?
As renal function diminishes, the hemoglobin A1c (HbA1c)-lowering effects of dapagliflozin also decline, according to a recent study.
Researchers already know that inhibiting sodium glucose cotransporter 2 with dapagliflozin reduces HbA1c, body weight, blood pressure, and albuminuria (urinary albumin-to-creatinine ratio). Dapagliflozin also can lead to small increases in hematocrit, which are probably related to osmotic diuresis/natriuresis.
The investigators undertook the current study to better understand the impact of dapagliflozin on other cardiovascular risk factors at different estimated glomerular filtration rate (eGFR) levels.
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In a pooled analysis, Hiddo J.L. Heerspink, PharmD, PhD, and colleagues, examined 11 phase 3 clinical trials that compared 10 mg dapagliflozin with placebo over a 24-week period in patients with type 2 diabetes as determined by baseline eGFR. Factors assessed for change were HbA1c, body weight, blood pressure, hematocrit, and urinary albumin-to-creatinine ratio.
Results indicated that patients who received dapagliflozin experienced reductions in HbA1C that were 0.6%, 0.5%, and 0.3%, respectively, for each consecutive lower eGFR subgroup.
Additionally, regardless of baseline eGFR, dapagliflozin similarly effected hematocrit, body weight, and blood pressure. This finding suggested “that effects potentially related to volume and natriuresis are eGFR independent,” the study’s authors wrote.
In participants who had a baseline urinary albumin-to-creatinine ratio that was ≥30 mg/g, reductions in urinary albumin-to-creatinine ratio that were adjusted for placebo were greater in the subgroup with the lowest eGFR.
Among the lowest eGFR subgroup, both patients treated with dapagliflozin and patients treated with placebo had more adverse events.
The study’s authors concluded that “dapagliflozin consistently decreases body weight, blood pressure, 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.”
—Lauren LeBano
Reference
Petrykiv S, Sjöström CD, Greasley PJ, Xu J. Differential effects of dapagliflozin on cardiovascular risk factors at varying degrees of renal function. Clin J Am Soc Nephrol. 2017;12(5):751-759.