Cystatin C Confirms the Canagliflozin eGFR Slope Benefit in CANPIONE

In the canagliflozin in type 2 diabetic patients with microalbuminuria in Japanese population (CANPIONE) study with a novel preintervention slope design, canagliflozin attenuated the decline in creatinine-based estimated glomerular filtration rate (eGFR-creatinine) slope in patients with type 2 diabetes mellitus and microalbuminuria. However, because serum creatinine is affected by muscle mass, the reliability of the eGFR-creatinine slope may be limited. Therefore, this prespecified exploratory analysis aimed to evaluate the effect of canagliflozin on the cystatin C-based eGFR (eGFR-cystatin C) slope, which is less affected by muscle mass, to validate the robustness of the previous findings.

The chronic eGFR-cystatin C and eGFR-creatinine slopes were assessed using a 2-slope linear spline mixed-effects model. Pearson correlation coefficients were used to evaluate associations between changes in eGFR and body composition-related parameters.

eGFR trajectories were directionally consistent across both filtration markers. The chronic eGFR-cystatin C slopes in the canagliflozin and control groups were -0.4 (95% confidence interval [CI], -2.6 to 1.8) and -4.9 (-7.1 to -2.6) ml/min per 1.73 m²/year, respectively, corresponding to a between-group difference of 4.4 (1.3-7.6) ml/min per 1.73 m²/year. Similar trends were observed in the eGFR-creatinine slopes derived from the same time points, yielding a comparable treatment effect on the chronic slope (between-group difference: 3.5 [0.2-6.8] ml/min per 1.73 m²/year). Canagliflozin reduced body weight, body mass index (BMI), and waist circumference, whereas little correlation was observed between these changes and changes in eGFR-cystatin C.

Incorporating the eGFR-cystatin C slope analysis supports the robustness of the previous creatinine-based slope findings, suggesting that the eGFR-creatinine slope analysis retains reasonable clinical reliability in patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is).