Sodium–Glucose Cotransporter-2 Inhibitors and Prevention of Adverse Kidney Outcomes in Type 2 Diabetes: A Clinical Multiethnic Asian Cohort

Abstract

Rationale & Objective

Studies of sodium-glucose cotransporter-2 (SGLT2) inhibitors assessing kidney outcomes among Asians with type 2 diabetes in a clinical setting are limited. We assessed the association of SGLT2 inhibitors with kidney and safety outcomes in a diverse multiethnic Asian population with type 2 diabetes in a clinical setting.

Study Design

Retrospective cohort study.

Setting & Participants

Patients with type 2 diabetes from multi-institutional SingHealth Diabetes Registry in Singapore.

Exposure

Initiators of SGLT2 inhibitors between 2014 to 2018 with a median follow-up duration of 25.6 months (interquartile range, 17.9-31.4).

Outcomes

Composite kidney outcome (≥40% estimated glomerular filtration rate [eGFR] decline or incident kidney failure with replacement therapy [KFRT]), its components, rate of eGFR change, amputation, and acute kidney injury (AKI).

Analytical Approach

Propensity scores for SGLT2 inhibitors initiation were developed, with 1:1 matching with initiators of other antidiabetic drugs. Cox proportional hazards and linear mixed effect models were employed.

Results

After matching, there were 4,254 patients newly initiated on either SGLT-2 inhibitors or other glucose-lowering drugs (2,127 in each group). The mean age was 63.4 (SD 9.2) years, with 48.6% women. In total, 67.8% of participants were Chinese, 11.9% Indian, 15.6% Malay, and 4.7% others. Initiating SGLT2 inhibitors was associated with lower risks of composite kidney outcome (hazard ratio [HR], 0.39; 95% CI, 0.31-0.48) and ≥40% reduction in eGFR from baseline (HR, 0.38; 95% CI, 0.31-0.48). SGLT2 inhibitor initiation was also associated with a slower eGFR decline among the intention-to-treat population (n = 1,888, difference in slope: 2.67 mL/min per 1.73 m² per year; 95% CI, 1.90-3.43). No significant association with amputation was found, though SGLT2 inhibitors were associated with reduced AKI risk.

Limitations

Potential informed presence bias and residual and unmeasured confounding.

Conclusions

SGLT2 inhibitors significantly benefit kidney outcomes in multiethnic Asians with type 2 diabetes, highlighting their role in preventing kidney complications.

Plain Language Summary

Real-world evidence on the kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors among Asians with type 2 diabetes is limited. This study examined the effects of SGLT2 inhibitors on kidney and safety outcomes in a diverse group with type 2 diabetes in Singapore. Data from 2,127 patients initiating SGLT2 inhibitors were matched 1:1 with other glucose-lowering drugs users using propensity scores. Over a median follow-up of 25.6 months, SGLT2 inhibitors were linked to a 61% lower risk of significant kidney function decline and a slower rate of kidney function loss than other glucose-lowering drugs. Importantly, their use did not increase the risk of amputation or acute kidney injury. These findings support their role in kidney protection in Asian populations with diabetes.