The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) reduces HbA1c, weight and blood pressure (BP) in patients with type 2 diabetes mellitus (T2DM).  While glucose lowering with EMPA is dependent on renal function, it is less well under stood how chronic kidney disease (CKD) influences BP moderation with EMPA.  In five randomized Phase III trials, 2286 patients with T2DM received EMPA 25 mg or placebo (PBO) for 24 weeks as monotherapy or add-on therapy.  Using pooled data from these trials, we assessed changes from baseline in systolic BP (SBP) and HbA1c with EMPA 25 mg vs PBO in subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease equation), adjusting for differences in baseline SBP (SBP analyses only), HbA1c, region, treatment, study, eGFR and treatment by eGFR interaction between groups.  In patients with normal renal function, or stage 2 or 3 CKD, EMPA significantly reduced HbA1c and SBP versus PBO.  As expected, placebo-corrected HbA1c reductions with EMPA decreased with decreasing eGFR.  In contrast, PBO-corrected reductions in SBP with EMPA appeared to be maintained with decreasing eGFR.  Unlike HbA1c, reductions in SBP with EMPA in patients with T2DM appeared to be maintained in patients with lower eGFR, indicating that SBP modulation with EMPA may involve pathways other than urinary glucose excretion such as diuretic effects, weight loss, reduced arterial stiffness, or direct vascular effects.

This study was sponsored by Boehringer Ingelheim.