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SGLT2 inhibitors yield fewer acute kidney injury events
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Patients with type 2 diabetes who were prescribed SGLT2 inhibitors experienced fewer acute kidney injury events after 14 months than those not using SGLT2 inhibitor therapy, according to a study.
“SGLT2 inhibitors are a novel class of medications that have been recently demonstrated to provide significant benefits in patients with type 2 diabetes; however, there was concern of acute kidney injury associated with these medications based on case reports and reports made to the FDA,” Girish N. Nadkarni, MD, MPH, CPH, told Endocrine Today. “The reports of acute kidney injury did not have a comparator group; thus, the risk attributable to SGLT2 inhibitors was unclear because it is well-known that patients with type 2 diabetes are already at high baseline risk of developing acute kidney injury.”
Nadkarni and colleagues analyzed longitudinal electronic medical records data from the Mount Sinai Chronic Kidney Disease Registry and the Geisinger Health System cohort from 377 patients with type 2 diabetes prescribed the SGLT2 inhibitors canagliflozin (Invokana, Janssen), empagliflozin (Jardiance, Boehringer Ingelheim) or dapagliflozin (Farxiga, AstraZeneca), and 377 patients with type 2 diabetes not using SGLT2 inhibitors. Researchers determined cases of acute kidney injury using a laboratory-based algorithm and performed 1:1 nearest-neighbor propensity matching and calculated HRs for acute kidney injury.
In the Mount Sinai cohort of SGLT2 users, 71.8% of patients were prescribed canagliflozin, 19.4% were prescribed dapagliflozin and 8.9% were prescribed empagliflozin.
During a median follow-up of 14 months, 3.8% of patients in the SGLT2 cohort and 9.7% of patients in the non-SGLT2 cohort experienced acute kidney injury.
HR for acute kidney injury was 60% lower in SGLT2 users vs. nonusers (HR = 0.4; 95% CI, 0.2-0.7); results persisted after adjustment for metformin use, HbA1c, smoking, thiazide use and race (P = .004).
Similarly, researchers identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2% and 4.6%, respectively, experienced acute kidney injury.
“We showed that there was no increased acute kidney injury in patients with type 2 diabetes prescribed SGLT2 inhibitors compared to those not on these medications with more than a year of follow-up,” Nadkarni said. “In fact, these patients had a lower risk of acute kidney injury. Using our data, we were also able to demonstrate that the acute kidney injury that did occur had less of a peak rise in serum creatinine. Thus, the frequency and severity of acute kidney injury was less.”
The association persisted, Nadkarni noted, when looking at subgroups, including patients with CKD or those on different background therapies.
“Thus, consideration of this risk should discourage inappropriate avoidance of these medications, especially considering the significant cardiac and renal protection conferred by these medications,” Nadkarni said.
He noted that some patients may develop an acute worsening of their kidney function that is likely hemodynamic, due to sodium and water loss and blood pressure changes from the SGLT2 inhibition.
“This type of acute kidney injury is usually reversible and short-lived without any long-term, worse outcomes,” Nadkarni said. “Better elucidation of the etiology and mechanisms is needed for those who do experience acute kidney injury. If newer tools can be employed to prove that an episode of SGLT2 inhibitor-associated acute kidney injury is of hemodynamic etiology and not actual kidney injury, health providers would feel more comfortable prescribing these novel medications.” – by Regina Schaffer
For more information:
Girish N. Nadkarni, MD, MPH, CPH, can be reached at the Icahn School of Medicine at Mount Sinai, Department of Nephrology, 1468 Madison Ave., New York, NY 10029; email: girish.nadkarni@mountsinai.org.
Disclosures: The authors report no relevant financial disclosures.
Perspective
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There are three lines of evidence: Adverse event reporting in clinical trials, renal outcomes in clinical trials and real-world evidence. The balance of the evidence suggests that it is rare that patients get into trouble with dehydration and that many benefit with regard to renal regulation and long-term outcomes. Net, I believe SGLT2 inhibitors are good for the kidneys.
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