942-P: Renal Outcomes Associated with Canagliflozin 100 mg and Subsequent Intensification to Canagliflozin 300 mg in Patients with Type 2 Diabetes Mellitus in the INTENSIFY Study

Objective: This analysis, based on the multicentric observational study INTENSIFY, aimed to evaluate renal outcomes associated with canagliflozin 100 mg/d (CANA100), as add-on to the background antihyperglycemic therapy, and later intensification by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2. Methods: A total of 317 patients (59.6% men, mean age 60.9 y, A1c 8.4%, BMI 33.1 kg/m2, systolic BP (SBP) 138.9 mmHg, eGFR 87.9 ml/min/1.73 m2, urine albumin-to-creatinine ratio (UACR) >30 mg/g 28.6%) were included, with a median follow-up of 38.8 months. Primary outcomes were changes in UACR and eGFR over the follow-up. Results: Treatment with CANA100 and subsequent switch to CANA300 led to significant reductions in UACR (mean change -44.8 mg/g, p 0.008). The percentage of patients with UACR 30-300 mg/g significantly decreased from 22.2% to 16.0% and the percentage of those with UACR >300 mg/g lowered from 6.4% to 2.0% (p 0.005). There was a significant decrease in eGFR (-4.0%, p < 0.0001) over the follow-up. The eGFR slope in the maintenance phase (after the first 6 months) was -0.21 ml/min/1.73 m2 per year. Intensification to CANA300 induced an additional reduction in UACR without a significant drop in eGFR. Patients achieved a statistically significant overall reduction in A1c (-1.30%), weight (-5.8 kg), SBP (-9.6 mmHg), and DBP (-4.7 mmHg), at the end of the follow-up, all p < 0.0001. There was a numerical reduction in the use of diuretics; no significant changes in ACEs/ARBs therapy were observed. Only 2 patients (0.6%) experienced episodes of volume depletion. Conclusion: Sequential treatment with CANA100 and later switch to CANA300 was associated with a significant improvement in UACR, likely due to multifactorial effects of the drug.