Impact of the initial decline in the estimated glomerular filtration rate on the risk of new-onset atrial fibrillation and adverse cardiovascular and renal events in patients with type 2 diabetes mellitus treated with sodium-glucose cotransporter 2 inhibitor.

Aim Sodium-glucose cotransporter 2 inhibitors (SGLT2is) cause an initial decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). The effect of different eGFR decline following SGLT2i treatment on risks of atrial fibrillation (AF), cardiovascular, and renal events in patients with T2DM are unknown. Materials and methods We used medical data from a multicenter health care provider in Taiwan and recruited 11 769 T2DM patients with baseline/follow-up eGFR data available after 1-3 months of SGLT2i treatment from June 1, 2016, to December 31, 2018. Patients were followed up from drug index date until the occurrence of adverse clinical events, SGLT2i discontinuation, or the end of the study period, whichever occurred first. Results Overall, SGLT2i treatment was associated with an initial eGFR decline of 3.5% ± 17.0% after a median treatment period of 10 weeks. A total of 37.1%(n = 4371) of patients experienced no eGFR decline, and 30.5%(n = 3593), 20.2%(n = 2376), 8.5%(n = 999), and 3.7%(n = 430) of patients experienced an eGFR decline of 0%-10%, 10%-20%, 20%-30%, and > 30%, respectively. The mean eGFR over time became stable after 6 months in all eGFR decline categories, even in the group with a pronounced eGFR decline of >30%. Compared with no eGFR decline, an initial eGFR decline of 0%-10%, 10%-20%, and 20%-30% was not associated with a higher risk of AF, major adverse cardiovascular events (including ischemic stroke, systemic embolism, and acute myocardial infarction)/heart failure (MACE/HF), and composite renal outcome (doubling of the serum creatinine level/end-stage kidney disease), whereas an eGFR decline of >30% was associated with a higher risk of new-onset AF (adjusted hazard ratio [aHR] = 2.20, 95% confidence interval [CI] = 1.40-3.47]), MACE/HF (aHR = 2.09, 95%CI = 1.04-4.17), and composite renal outcome (aHR = 1.82, 95%CI = 1.18-2.83). The multivariate analysis indicated that the use of diuretic or insulin, presence of stroke, older age, female in gender, a higher HbA1c level, and a lower BMI of 30% following SGLT2i initiation. Conclusions A pronounced eGFR decline >30% following SGLT2i treatment was associated with adverse cardiovascular or renal events among diabetic patients. This article is protected by copyright. All rights reserved.