April 1, 2021Diabetes Obesity and MetabolismOpen Access

Lower heart failure and chronic kidney disease risks associated with sodium‐glucose cotransporter‐2 inhibitor use in Japanese type 2 diabetes patients without established cardiovascular and renal diseases

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Why the study?

To examine heart failure and chronic kidney disease risk reductions associated with SGLT-2 inhibitors compared with other glucose-lowering drugs in early-stage type 2 diabetes patients without established cardiovascular or renal diseases.

Does SGLT-2i initiation reduce the risk of cardiorenal disease in Japanese type 2 diabetes patients without established cardiovascular or renal diseases compared to other glucose-lowering drugs?

Structured PICO

Does SGLT-2i initiation reduce the risk of cardiorenal disease in Japanese type 2 diabetes patients without established cardiovascular or renal diseases compared to other glucose-lowering drugs?

Population

108,362 Japanese patients with type 2 diabetes without established cardiovascular or renal diseases (CVRD-free T2D), mean age 59.1 years, 63% male.

Intervention

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) initiation

Comparator

Other glucose-lowering drugs (oGLD) initiation (1:1 propensity-score matched)

Outcome

Cardiorenal disease (composite of heart failure and/or chronic kidney disease)composite

In Japanese patients with type 2 diabetes without established cardiovascular or renal disease, initiation of SGLT-2 inhibitors is associated with a significantly lower risk of cardiorenal diseases, stroke, and all-cause mortality compared to other glucose-lowering drugs.

Implication

SGLT-2i associated with lower HF/CKD risk in CVRD-free T2D; hypothesis-generating and requires RCT confirmation before practice change.

Abstract

AIMS: To examine heart failure (HF) and chronic kidney disease (CKD) risks reduction associated with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to other glucose-lowering drugs (oGLD) in the early stage of type 2 diabetes patients without established cardiovascular or renal diseases (CVRD-free T2D). MATERIALS AND METHODS: We performed an observational cohort study using a Japanese hospital claims registry, Medical Data Vision. CVRD-free T2D patients were identified between 1 April 2014 and 30 September 2018. SGLT-2i and oGLD new users (and dipeptidyl peptidase 4 inhibitors [DPP-4i] separately) were subjected to 1:1 propensity-score matching analysis. Hazard ratios (HRs) of cardiorenal disease (HF and/or CKD), HF, CKD, stroke, myocardial infarction (MI), and all-cause mortality, were estimated using unadjusted Cox regression. RESULTS: A total of 108 362 CVRD-free patients including 54 181 SGLT-2i and 54 181 oGLD users were matched. Baseline characteristics were well balanced (mean age 59.1 years, 63% male, and follow-up 1.50 years [162 970 patient-years]). Compared to oGLD group, SGLT-2i group had lower risk of cardiorenal disease, HF, CKD, stroke, and all-cause mortality with HRs (95% confidence intervals) 0.55 (0.49-0.61), 0.73 (0.61-0.87), 0.45 (0.39-0.52), 0.69 (0.59-0.81), and 0.52 (0.46-0.58), respectively, while no difference in MI. These were consistent in 1:1 propensity-score matching analysis between SGLT-2i and DPP-4i users (n = 17 232 in each group). CONCLUSIONS: In Japanese CVRD-free T2D patients, SGLT-2i initiation was associated with lower risk of cardiorenal diseases, stroke, and all-cause mortality compared to oGLD, suggesting preventive effect of SGLT-2i treatment in the early stage of T2D patients without CVRD manifestation.