Long-term preservation of kidney function with SGLT-2 inhibitors versus comparator drugs in people with type 2 diabetes and chronic kidney disease

Abstract

Aims: Chronic kidney disease (CKD) is a prevalent and serious complication of type 2 diabetes (T2D). This study aims to evaluate kidney outcomes in a real-world cohort of patients with T2D and CKD who received SGLT2 inhibitors (SGLT2i) or other glucose-lowering medications (GLM).

Materials and methods: This retrospective, multicentre study analysed data from patients aged 18-80 years with T2D and CKD, who initiated an SGLT2i or other GLM between 2015 and 2020. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over time. Secondary outcomes included albuminuria changes and adverse kidney events. Propensity score matching was used to balance baseline characteristics between the two groups.

Results: After matching (n = 2020/group), patients (100% T2D with CKD) had a mean age of 63 years, BMI 32 kg/m², HbA1c 8.2%. New-users of SGLT2i exhibited a slower decline in eGFR compared with new users of comparators (mean difference 1.43 mL/min/1.73 m²; p = 0.048). Albuminuria improved significantly more in the SGLT2i group, with a greater likelihood of category improvement (hazard ratio [HR] 1.17; p = 0.007). SGLT2i initiation was associated with a lower incidence of kidney outcomes, including a ≥40% eGFR reduction (HR 0.63; p = 0.004). When the comparison was restricted to SGLT2i versus GLP-1RA (n = 1266/group), the eGFR slope was significantly better with SGLT2i (mean difference 0.62 mL/min/1.73 m²/year; p = 0.046).

Conclusions: In this large, real-world cohort, initiation of SGLT2i was associated with a significantly slower decline in kidney function and improved albuminuria compared with other diabetes drugs, including GLP-1RA. These findings support SGLT2i as the most effective T2D treatment to slow CKD progression.

Keywords: gliflozin; observational; outcomes; renal; retrospective.

FIGURE 1

Estimated glomerular filtration rate (eGFR)‐based outcomes. (A) Change in eGFR over time in the two groups. The table shows number of patients contributing to the analysis at each timepoint. (B) eGFR slopes before and after index date. (C, D) Event rate curves for the ≥40% (C) or ≥57% loss of kidney function. The table shows the number of patients at risk at each timepoint. CI, confidence interval; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; HR, hazard ratio; SGLT2i, sodium–glucose cotransporter 2 inhibitors.

FIGURE 2

Albuminuria‐based outcomes. (A) Change in the urinary albumin excretion rate (UACR) over time. The table shows number of patients contributing to the analysis at each timepoint. (B) Event rate curves for the extended composite outcome including ≥40% loss of kidney function, new‐onset macroalbuminuria, end‐stage kidney disease, or dialysis. The table shows the number of patients at risk at each timepoint. CI, confidence interval; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; HR, hazard ratio; SGLT2i, sodium–glucose cotransporter 2 inhibitors.