SGLT2 inhibitor reduces CV risk factors in patients with and without renal dysfunction
Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal FunctionLiterature - Petrykiv S, Sjöström DC, Greasley PJ, et al. - Clin J Am Soc Nephrol 2017; published online ahead of print
- Out of 4404 patients, 1394 had an eGFR ≥90 ml/min per 1.73 m2, 2484 had an eGFR between ≥60 and <90 ml/min per 1.73 m2, and 526 had an eGFR between ≥45 and <60 ml/min per 1.73 m2.
- Patients with an eGFR between ≥45 and <60 ml/min per 1.73 m2 at baseline were older, more likely to be women, had a higher body weight and a longer duration of diabetes mellitus.
- After 24 weeks of therapy, the placebo-corrected reduction in urinary glucose-to-creatinine ratio with dapagliflozin was progressively smaller in patients with eGFR ≥45 and <60 ml/min per 1.73 m2 compared with patients with eGFR ≥60 and <90 ml/min per 1.73 m2 and patients with eGFR ≥90 ml/min per 1.73 m2.
- Compared with placebo, reductions in HbA1c after 24 weeks of treatment with dapagliflozin in the eGFR subgroups were 0.6%, 0.5% and 0.3% (P interaction <0.001).
- Compared with placebo, 24 weeks of treatment with dapagliflozin led to similar SBP changes in the eGFR subgroups: 23.4 mmHg (95% CI: 24.6 - 22.1), 22.6 mmHg (95% CI: 23.6 - 21.6), and 24.3 mmHg (95% CI: 26.8 - 21.8).
- Compared with placebo, reductions in albuminuria, haematocrit, bicarbonate, body weight, pulse pressure and uric acid were similar between eGFR subgroups.
- Compared with placebo, dapagliflozin caused an initial eGFR decrease in each subgroup. At week 4, the placebo-corrected changes in eGFR were 22.1 ml/min per 1.73m2 (95% CI: 23.5-20.7), 23.0 ml/min per 1.73m2 (95% CI: 23.7-22.2) and 22.9 ml/min per 1.73m2 (95% CI: 24.3-21.6).
- Weak correlations between changes in HbA1c and changes in SBP or body weight were observed in all eGFR subgroups.
- A higher overall rate of adverse events and serious adverse events was observed in patients in the lowest eGFR group, but this was true for both the placebo and dapagliflozin groups.
Dapagliflozin consistently reduced blood pressure, body weight and albuminuria, independently of baseline renal function. These findings suggest that further research of the long-term benefits of SGLT2 inhibitors in patients with diabetic kidney disease might be needed.