Diabetes is a leading cause of chronic kidney disease (CKD) worldwide. Optimum glycaemic control in patients with type 2 diabetes is important to minimise the risk of microvascular and macrovascular complications and to slow the progression of CKD. We assessed the efficacy and safety of empagliflozin as an add-on treatment in patients with type 2 diabetes and CKD.

We did a phase 3, randomised, double-blind, parallel-group, placebo-controlled trial at 127 centres in 15 countries. Patients with HbA_1c of 7% or greater to 10% or less were eligible for inclusion. Patients with stage 2 CKD (estimated glomerular filtration rate [eGFR] ≥60 to <90 mL/min per 1·73 m²; n=290) were randomly assigned (1:1:1) to receive empagliflozin 10 mg or 25 mg or placebo once daily for 52 weeks. Patients with stage 3 CKD (eGFR ≥30 to <60 mL/min per 1·73 m²; n=374) were randomly assigned (1:1) to receive empagliflozin 25 mg or placebo for 52 weeks. Randomisation was done with a computer-generated random sequence and stratified by renal impairment, HbA_1c, and background antidiabetes medication. Treatment assignment was masked from patients and investigators. The primary endpoint was change from baseline in HbA_1c at week 24 by ANCOVA in the full analysis set. This study is registered with ClinicalTrials.gov, number NCT01164501.

In patients with stage 2 CKD, adjusted mean treatment differences versus placebo in changes from baseline in HbA_1c at week 24 were −0·52% (95% CI −0·72 to −0·32) for empagliflozin 10 mg and −0·68% (–0·88 to −0·49) for empagliflozin 25 mg (both p<0·0001). In patients with stage 3 CKD, adjusted mean treatment difference versus placebo in change from baseline in HbA_1c at week 24 was −0·42% (–0·56 to −0·28) for empagliflozin 25 mg (p<0·0001). In patients with stage 2 CKD, adverse events were reported over 52 weeks by 83 patients (87%) on placebo (15 severe [16%] and 11 serious [12%]), 86 (88%) on empagliflozin 10 mg (six severe [6%] and six serious [6%]) and 78 (80%) on empagliflozin 25 mg (eight severe [8%] and seven serious [7%]). In patients with stage 3 CKD, adverse events were reported over 52 weeks by 156 patients (83%) on placebo (15 severe [8%] and 23 serious [12%]) and 156 (83%) on empagliflozin 25 mg (18 severe [10%] and 22 serious [12%]).

In patients with type 2 diabetes and stage 2 or 3 CKD, empagliflozin reduced HbA_1c and was well tolerated. However, our findings might not be applicable to the general population of patients with type 2 diabetes and renal impairment.

Boehringer Ingelheim, Eli Lilly.