SGLT2 inhibitors provide renoprotection in Asians

Real-world use of sodium-glucose cotransporter 2 (SGLT2) inhibitors can stem the progression of chronic kidney disease (CKD) and the development of end-stage kidney disease (ESKD) in a multi-ethnic Asian population, according to a study.

SGLT2 inhibitors significantly lowered the risk of adverse renal outcomes, including the decline of eGFR, in patients with moderate-to-advanced CKD (eGFR 15–44 mL/min/1.73 m²), said a team of investigators led by Dr Allen Liu of Khoo Teck Puat Hospital, Singapore.

Meanwhile, the effects of the drugs in patients with early CKD (eGFR ≥45 mL/min/1.73 m²) were less pronounced, Liu added.

The analysis included a cohort of 4,446 type 2 diabetes mellitus (T2DM) patients (mean age 60.6 years, 52.4 percent male, 57.7 percent Chinese) seen in a regional hospital in Singapore. A total of 3,220 and 1,226 patients had early and moderate-to-advanced CKD, respectively, among whom 1,598 (49.6 percent) and 1,086 (88.6 percent) received SGLT2 inhibitors.

Over a median follow-up of 1.4 years, treatment with SGLT2 inhibitors significantly reduced the risk of CKD progression by 40–57 percent in the entire cohort (hazard ratio [HR], 0.60, 95 percent confidence interval [CI], 0.49–0.74; p<0.001) as well as in the early CKD (HR, 0.60, 95 percent CI, 0.47–0.76; p<0.001) and the moderate-to-advanced CKD (HR, 0.43, 95 percent CI, 0.23–0.66; p<0.001) subgroups. [Clin Kidney J 2022;15:1403-1414]

The risk of developing ESKD also markedly decreased with SGLT2 inhibitors for the entire cohort (HR, 0.33, 95 percent CI, 0.17–0.65; p=0.001) and the moderate-to-advanced CKD subgroup only (HR, 0.24, 95 percent CI, 0.09–0.66; p=0.006).

“Although all three SGLT2 inhibitors reduced the risk of CKD progression, empagliflozin was more likely to exert sustained renoprotection from early to advanced CKD,” Liu noted.

Renoprotection more profound in real world 

“Our results from real-world practice revealed comparable risk reduction on CKD progression in randomized controlled trials with renal composite outcomes as primary and secondary endpoints. On the other hand, we found that empagliflozin [yielded a greater reduction in the] risk of developing ESKD, contrary to the EMPA-REG,” according to Liu. [N Engl J Med 2019;380:2295-2306; N Engl J Med 2020;383:1436-1446; Diabetes Investig 2019;10:760-770; J Am Soc Nephrol 2020;31:1128-1139; Lancet Diabetes Endocrinol 2019;7:606-617]

Furthermore, compared with meta-analyses that demonstrated attenuated proportional effects on renoprotection with declining kidney function, the current study showed the reverse effect, with a more significant reduction in the risk of CKD progression and ESKD in patients with advanced vs early-stage CKD, he continued. [Lancet Diabetes Endocrinol 2019;7:845-854; Cardiovasc Diabetol 2021;20:83]

“Our cohort is from a region with one of the highest incidences of ESKD secondary to diabetic kidney disease (DKD). In this study, 9.9 percent of patients developed ESKD, compared with 0.37 percent in EMPA-REG and 0.2 percent in CANVAS. Therefore, the benefits of SGLT2 inhibitors on renoprotection may be more profound in real-world practice when prescribed in a highly prevalent DKD population,” Liu pointed out.

Despite the presence of limitations, including the varying doses of SGLT2 inhibitors prescribed to patients varied across the nephrology and endocrinology teams and the lack of data on adverse events relating to treatment, the current real-world study is the first to include patients with moderate-to-advanced CKD to evaluate the risk of CKD progression and ESKD incidence in a highly prevalent DKD population, Liu said.

“Moreover, this study provides a more comprehensive view of how SGLT2 inhibitors could alleviate the renal disease burden in the community. It also offers crucial information to policymakers on implementing public health measures and reimbursements on using SGLT2 inhibitors from tertiary to primary care,” he added.