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

Aim To investigate the impact of initial decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes (T2D) following sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment. Materials and Methods We used medical data from a multicentre healthcare provider in Taiwan and recruited 11 769 patients with T2D with baseline/follow-up eGFR data available after 1 to 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2018. Patients were followed up from the drug index date until the occurrence of adverse clinical events, SGLT2i discontinuation or the end of the study period, whichever took place first. Results Overall, SGLT2i treatment was associated with an initial eGFR decline of 3.5% +/- 14.0% 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 more than 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 more than 30%. Compared with no eGFR decline, an initial eGFR decline of 0%-10%, 10%-20% or 20%-30% was not associated with a higher risk of atrial fibrillation (AF), major adverse cardiovascular events (MACE, including ischaemic stroke, systemic embolism and acute myocardial infarction)/heart failure (HF) and composite renal outcome (doubling of the serum creatinine level/end-stage kidney disease), whereas an eGFR decline of more than 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 a diuretic or insulin, presence of stroke, older age, female sex, a higher HbA1c level, and a lower body mass index of less than 25 kg/m(2) were independent factors associated with an eGFR decline of more than 30% following SGLT2i initiation. Conclusions A pronounced eGFR decline of more than 30% following SGLT2i treatment was associated with adverse cardiovascular or renal events among patients with T2D.