PracticeUpdate Conference Series ISN WCN 2019

SGLT2 Inhibitors Benefit Patients With Diabetes and Chronic Kidney Disease Loosening restrictions on use of SGLT2 inhibitors among patients with diabetic kidney disease should be considered. S GLT2 inhibitors reduce the risk of cardiovascular events and slow the loss of kidney function in patients with type 2 diabetes and chronic kidney disease, according to a meta-analysis presented at WCN 2019. The study found no evidence of additional safety concerns with the use of SGLT2 inhibitors. SGLT2 inhibitors are a newer treatment for type 2 diabetes, but they are not currently approved for use in people with reduced kidney function because they are less effective at lowering blood glucose levels in this population, study presenter Brendon Neuen, MBBS, of the George Institute for Global Health based at the University of Oxford in the United Kingdom, told Elsevier’s PracticeUpdate . Current data suggest, however, that these drugs might reduce the risk of cardiovascular events and prevent the loss of kidney function in people with type 2 diabetes and chronic kidney disease. “We wanted to look at all the available data, frompublished studies to regulatory submissions, to determine the effect of SGLT2 inhibitors on cardiovascular, kidney, and safety outcomes in people with type 2 diabetes and chronic kidney disease,” said Dr. Neuen. Data were obtained from 27 studies involving up to 7363 patients. Among individuals with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors reduced the risk of the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a risk ratio of 0.81 (95%CI 0.70–0.94) as well as hospitalization for heart failure, with a risk ratio of 0.61 (95% CI 0.48–0.78). SGLT2 inhibitors also attenuated the annual decline in kidney function by an annual estimated glomerular filtration rate (eGFR) mean slope difference of 1.35 mL/min/1.73 m 2 /year; 95% CI 0.78–1.93. There was also a reduction in the risk of developing the composite renal outcome of doubling of serum creatinine, end-stage kidney disease, or renal death (risk ratio 0.71, 95% CI 0.53–0.95). The researchers found no evidence of additional risks with SGLT2 inhibition in chronic kidney disease beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. “Our findings suggest that SGLT2 inhibitors reduce the risk of cardiovas- cular events and progression of kidney disease in people with type 2 diabetes and chronic kidney disease, despite only modest reductions in glycated hemoglobin [HbA1c],” said Dr. Neuen. In fact, HbA1c was lowered by only a mean of –0.29%; 95% CI –0.39 to –0.19. This suggests that the observed reductions in cardiovascular and kidney outcomes with SGLT2 inhibition are not being driven by improved glucose control. “Further, these data suggest that if restrictions on the use of these drugs in people with reduced kidney function are reconsidered, many more additional individuals might benefit from this treatment,” said Dr. Neuen. The research team’s findings are almost entirely consistent with the CREDENCE trial, the first dedicated renal outcome trial of an SGLT2 inhibitor (canagliflozin). “Taken together, these data suggest that SGLT2 inhibition will play an increasingly important role in the management of diabetic kidney disease moving forward,” said Dr. Neuen.

Patient-related outcome measures primarily associ- ated with fluid status, such as post-dialysis recovery time, headaches, dizziness, and cramps, were all less frequent and less severe among those treated with hemodiafiltration, compared with hemodialy- sis. In addition, there was less inter-dialytic weight gain on hemodiafiltration, which the investigators said implies lower ultrafiltration rates per session and greater hemodynamic stability was strongly associated with fewer symptoms. From a lifestyle perspective, children treated with hemodiafiltration had improved school attendance and greater physical activity scores, but there was no difference between the two groups with respect to hospitalization rates. “For patients on in-center dialysis, with equivalent dialysis-durations and blood flow rates, hemodia- filtration appears to be a safe and more effective dialysis modality than conventional hemodialy- sis,” Dr. Shroff said. “It is preferred by patients as post-dialysis recovery times are shorter, and this allows for better school attendance and greater physical activity scores. In addition, children on hemodiafiltration feel better, with fewer headaches and episodes of dizziness or cramps than children on hemodialysis.” Hemodiafiltration “is effective even in those who require a short period on dialysis, such as those who have a donor for transplantation, [as well as] for those with residual renal function,” she noted. Nevertheless, Dr. Shroff pointed out, “A randomized trial is required before hemodiafiltration can be considered the standard of care for children on in-center dialysis.”

www.practiceupdate.com/c/82722

www.practiceupdate.com/c/82731

WCN 2019 • PRACTICEUPDATE CONFERENCE SERIES 13