Endocrine Abstracts

Introduction: Empagliflozin has a well-established anti-albuminuric effect in patients with T2DM, but in almost all available trials the baseline blood pressure was well controlled with SB P<140 mmHg. We analyzed the impact of empagliflozin treatment in patients with T2DM and uncontrolled hypertension, and its relationship with the changes in HbA1c and SBP.

Methods: Retrospective analysis of the albuminuria, SBP and HbA1c data in patients with T2DM and high office blood pressure (SB P>140 mmHg) when starting empagliflozin therapy. Post-hoc mediation analyses were performed with SBP and HbA1c changes as mediators in order to quantify their relative contributions to the changes in albuminuria. All included patients gave informed consent. Patients who started or changed antihypertensive medication simultaneously with the onset of empagliflozin therapy were excluded. Data are given as mean ± sd.

Results: Data were obtained from 169 patients (59.8% women, age 64.5 ± 9.3 years) in the visit in which empagliflozin was started (10 mg day in almost all cases), and in a successive visit after 3-6 months. 101 patients were on ACEI or ARB (59.7%). Baseline HbA1c was 8.2 ± 1.6% and the change was -0.7 ± 0.3% (P=0.011, paired t-test). Baseline SBP was 167 ± 18 mmHg and the change was 7.3 ± 5.1 mmHg (P=0.007, paired t-test). At baseline, 83 (49%), 57 (34%) and 29 (17%); and successively 98 (58%), 48 (28%) and 23 (14%) had normoalbuminuria (<30 mg/g Cr), microalbuminuria (30-300 mg/g Cr) or macroalbuminuria (> 300 mg/g Cr), respectively. Albuminuria was reduced by 9% (CI 95%: 14%-4%, P=0.043) in patients with normoalbuminuria; by 29% (35%-23%, P=0.002) in patients with microalbuminuria, and by 38% (47%-29%, P=0.003) in patients with macroalbuminuria. The reduction in albuminuria was significantly correlated with those of HbA1c (Pearson’s R: 0.18; P=0.008) and SBP (Pearson’s R 0.26; P=0.003). Mediation analyses showed that 16% (CI 95%: 12-20%, P=0.011) of the reduction in albuminuria was mediated by HbA1c reduction, and 25% (19-31%, P=0.004) by SBP reduction, but 59% was independent of both mediators.

Conclusions: Empagliflozin therapy was associated with a clinically and statistically significant reduction in albuminuria in patients with T2DM and uncontrolled hypertension. Although the reductions in HbA1c and SBP clearly contributed to this effect, much of the reduction in albuminuria seems to be attributable to other mechanisms, most likely the restoration of the tubuloglomerular feedback.