Effectiveness of Empagliflozin-Linagliptin Fixed-Dose Combination on Chronic Kidney Disease Outcomes in Patients With Type 2 Diabetes in a Real-World Setting.

introductionOptimal management of chronic kidney disease (CKD) is essential in patients with type 2 diabetes mellitus (T2DM). Certain antihyperglycemic agents, such as empagliflozin, provide additional kidney protection beyond glycemic control, while linagliptin is renal-safe and associated with reductions in albuminuria. This retrospective study aimed to evaluate the long-term outcomes (at least one year) for CKD and T2DM with the innovator fixed-dose combination (FDC) of empagliflozin and linagliptin in sodium-glucose cotransporter-2 inhibitor (SGLT2-i)-naïve T2DM subjects who were previously uncontrolled on a dipeptidyl-peptidase-4 inhibitor (DPP4-i)-based regimen.

methodsThe study included case record analyses of T2DM patients followed in the outpatient setting for at least 12 months. Glycemic control and renal parameters, including estimated glomerular filtration rate (eGFR), eGFR slope, and changes in urine albumin-creatinine ratio (UACR), were evaluated.  Results: A total of 433 eligible case records were analyzed. Of the study participants, 63.3% were male, 54.1% had hypertension (HTN), and 10.3% had established atherosclerotic cardiovascular disease (ASCVD). A significant reduction in glycated hemoglobin (HbA1c) of 1.5% was observed from a baseline mean of 8.3 ± 1.7%, along with a mean body-weight reduction of 3.3 kg over 12 months of combination therapy. At baseline, the mean eGFR was 82.0 mL/min/1.73 m², with 20% of patients having an eGFR < 60 mL/min/1.73 m². The mean UACR was 207.8 mg/g, and 79% of patients had UACR ≥ 30 mg/g. An initial dip of 5.5% in mean eGFR (-4.5 mL/min/1.73 m²) was noted at three months following SGLT2-i initiation. After this early dip, the eGFR slope showed an upward trajectory and was 1.9 mL/min/1.73 m² above baseline at 12 months. A significant reduction in mean UACR of 142.9 mg/g was seen, decreasing from 207.8 mg/g at baseline to 64.9 mg/g at 12 months. At least a 30% reduction in UACR from baseline was achieved by 71.8% of patients. The odds of patients being in the A1 UACR category were 2.2-fold higher at 12 months.

conclusionIn this observational study, the use of FDC of empagliflozin and linagliptin for at least 12 months in T2DM patients previously uncontrolled on a DPP4-i-based regimen was associated with reductions in albuminuria and improvement in eGFR slope after the expected initial dip at three months. Improvements in glycemic control and body weight were also observed, regardless of underlying cardiometabolic risk. The potential renal benefits noted in this descriptive evidence warrant further evaluation.