Residual cardiorenal risk high after SGLT2 inhibitor initiation in diabetic CKD
medwireNews: People with type 2 diabetes and chronic kidney disease (CKD) have a high residual risk for cardiorenal events and high rates of treatment failure after initiation of sodium-glucose cotransporter (SGLT)2 inhibitors, real-world study findings indicate.
The cardiorenal event risks were particularly high among individuals with preexisting cardiovascular (CV) disease, report Linda Fried (University of Pittsburgh, Pennsylvania, USA) and co-authors in BMC Medicine.
Fried and team reviewed administrative health claims data for 6389 adults (mean age 65.5 years, 53% men) with type 2 diabetes and CKD who initiated SGLT2 inhibitors between 2012 and 2019.
During a mean follow-up period of approximately 42 weeks, the incidence of CV hospitalization was 26.0 cases per 1000 person–years.
Multivariate analysis of baseline characteristics showed that a history of atrial fibrillation, cancer, and peripheral vascular disease were each associated with a significantly increased risk for CV hospitalization at hazard ratios of 2.97, 1.83, and 1.67, respectively.
In addition, each increasing year of age increased the CV hospitalization risk a significant 1.03-fold, while the use of alpha blockers, nitrates, and antiplatelets were associated with 2.07-, 1.74-, and 1.57-fold increased risks, respectively.
The renal hospitalization rate during follow-up was 12.0 cases per 1000 person–years, and the risk for renal hospitalization was significantly elevated among people with respiratory failure (HR=2.44), hyperkalemia (HR=2.41), heart failure (HR=2.05), depression (HR=1.86), and loop diuretic use (HR=1.95). Black people were a significant three times more likely than White people to have a renal hospitalization.
The researchers also report the rate of hospitalization for acute kidney injury (AKI), at 22.8 events per 1000 person–years. Baseline atrial fibrillation, cancer, loop diuretic use, and peripheral vascular disease were associated with significant 2.74-, 1.77-, 1.75-, and 1.63-fold increased risks for AKI hospitalization, respectively, while Medicare beneficiaries were a significant 1.66 times more likely to experience this outcome than people with commercial insurance.
Fried et al note that more than half (55.0%) of the individuals they studied discontinued SGLT2 inhibitor use, with a median time to discontinuation of 204 days. The treatment failure rate, which also included people who initiated another type 2 diabetes drug or insulin, was 510.5 cases per 1000 person–years.
Baseline use of a dipeptidyl peptidase-4 inhibitor (HR=1.33) and experiencing diabetic ketoacidosis during follow-up (HR=2.43) were significantly associated with an increased risk for treatment failure in the overall population, whereas the risk was significantly decreased with baseline use of statins (HR=0.90), glucagon-like peptide (GLP)-1 receptor agonists (HR=0.80), basal insulin (HR=0.79), or both a GLP-1 receptor agonist and insulin (HR=0.77).
In the subgroup of Medicare beneficiaries (n=4105), volume depletion was associated with an increased treatment failure risk (HR=1.61).
“Ultimately, the residual risk, combined with the observed high treatment discontinuation rates of SGLT2 [inhibitors], reveals suboptimal treatment in a significant proportion of this vulnerable population and suggests the need for additional cardio- and renoprotective interventions,” Fried and team remark.
They conclude: “The clinical profiles of patients with high unmet needs must be further explored to achieve the best clinical outcomes.”
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