medwireNews: The small proportion of people who experience an estimated glomerular filtration rate (eGFR) fall of more than 30% on starting a sodium-glucose cotransporter (SGLT2) inhibitor may be at increased risk for adverse outcomes, research suggests.
Analysis of data from SGLT2 inhibitor cardiovascular outcome trials indicated that the transient fall in eGFR experienced by a majority of people with type 2 diabetes on starting the medication is not generally associated with an increased cardiorenal risk. However, an analysis of CREDENCE, in which all participants had chronic kidney disease at baseline, linked a fall greater than 30% to a potential increased risk, although this was based on just 89 participants.
The current study, based on healthcare data from 11,769 people with type 2 diabetes given an SGLT2 inhibitor in real-world practice, backs up this finding, showing an increased risk for major adverse cardiovascular events (MACE) or heart failure hospitalization, renal events (doubling of the serum creatinine level or end-stage kidney disease), and new-onset atrial fibrillation in this subgroup.
Just 3.7% of the population had an eGFR decrease of this magnitude over a median of 10 weeks after they started using an SGLT2 inhibitor. A further 8.5%, 20.2%, and 30.5% of participants had declines of 20–30%, 10–20%, and less than 10%, respectively, whereas 37.1% had no change in eGFR.
“These cutoff values were chosen based on those reported in the post hoc analysis of the CREDENCE and EMPA-REG OUTCOME trials that aimed to provide clinically relevant, memorable, and easy-to-apply cutoff values,” Pao-Hsien Chu (Chang Gung Memorial Hospital, Taoyuan, Taiwan) and co-researchers comment in Diabetes Obesity and Metabolism.
People in the groups with an eGFR reduction of greater than 0% but less than 30% did not have an increased risk for any of the adverse outcomes when compared with people with no eGFR reduction.
However, the risk in people with an eGFR reduction larger than 30% was increased by a significant 2.09-fold for MACE or heart failure hospitalization, 1.82-fold for renal outcomes, and 2.20-fold for new-onset atrial fibrillation. These associations were independent of factors including age, sex, diabetic duration, comorbidities, glycated hemoglobin, BMI, and medication use.
When the MACE and heart failure endpoints were considered separately, the researchers found a significant association with the former, but not the latter.
They also found that the risk for new-onset atrial fibrillation associated with a greater than 30% fall in eGFR was significantly increased irrespective of baseline eGFR. But for MACE/heart failure or renal outcomes, the risk was significantly elevated only in participants who had a starting eGFR lower than 60 mL/min per 1.73 m2.
Older age, female sex, higher glycated hemoglobin, BMI below 25 kg/m2, pre-existing stroke, and use of diuretics or insulin were all independently associated with an increased risk for an eGFR fall greater than 30%, which the team says is in line with the predictors identified in clinical trials.
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