Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents.

Abstract

We aimed to determine the efficacy and safety of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists to preventworsening urinary albumin-to-creatinine ratio as an early biomarker of diabetes kidney disease. A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n=76), GLP1ra added to SGLT2i (n=50) or GLP1ra plus SGLT2i from start (n=52), according to investigators´ best clinical judgement. Major outcomes assessed at 26weeks were changes in urine albumintocreatinine-ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. All patients (58.6% men, mean age 61.9±10.0years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2±0.9%, 109.9±19kg and 83.3±19.6mL/min/m2 , respectively. At 26weeks, we found significant reductions in HbA1c (1.16%), weight (5.17kg) and systolic blood pressure (8.13mmHg). The reduction in UACR was 15.14mg/g (95% CI 8.50-22.4) (-24.6±64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7mg/g; 95% CI: 54-296.5mg/g; P<.001. Patients with urinary albumin-to-creatinine ratio ≥30mg/g, showed a higher declines (63.18mg/g [95% CI 44.5-104.99]) (-56±65.9%). The greatest reduction in urinary albumin-to-creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7mg/g). The eGFR did not significantly change along the study period. Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control.