The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as add-on to the background antihyperglycemic therapy, and to evaluate the intensification of SGLT2 inhibitor (SGLT2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. 583 patients were included, 279 in the cohort of CANA100 (men 54.8%, age 59.7 y, A1C 8.05%, weight 94.9 kg) and 304 in the cohort of CANA 300 (men 55.9%, age 61.1 y, A1C 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. The primary outcome of the study was the mean change in A1C over the follow-up time. CANA100 was associated to significant reductions in A1C (-0.90%), weight (-4.1 kg) and systolic BP (-4.8 mmHg) at the end of the follow-up. The percentage of patients with A1C<7% significantly increased from 25.2% to 50.6%. In those patients with poor glycemic control (A1C >8%, mean 9.2%) CANA100 lowered A1C levels by 1.51%. There was a significant decrease in serum uric acid and liver enzymes. In the second cohort, patients with prior background SGLT2i therapy (dapagliflozin 10 mg 51%, CANA100 30.6%, empagliflozin 10/25 mg 7.3%/11.1%) switched to CANA300. Significant improvements in A1C (-0.35%), weight (-2.1 kg) and systolic BP (-3.2 mmHg) were observed over the follow-up period. There was a significant decrease in liver enzymes after SGLT2i intensification with CANA300. The percentage of patients with A1C<7% significantly increased from 28.9% to 46.6%. In those patients with poor glycemic control (A1C >8%, mean 8.9%) CANA300 lowered A1C levels by 1.12%. No unexpected adverse events were reported. In summary, CANA100 (as add-on therapy) and CANA300 (switching from CANA100 or other SGLT2i) significantly improved several cardiometabolic parameters in patients with T2DM. Disclosure J.J. Gorgojo-Martinez: Advisory Panel; Self; Abbott, AstraZeneca, Grunenthal Group, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Mundipharma International, Novo Nordisk Inc., Pfizer Inc. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Mundipharma International, Novo Nordisk Inc. M.A. Gargallo-Fernandez: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi. A. Galdon: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Mundipharma International, Novo Nordisk Inc. T. Antón-Bravo: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Mundipharma International, Novo Nordisk Inc. M. Brito-Sanfiel: Advisory Panel; Self; Abbott, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker’s Bureau; Self; Almirall, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Esteve, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mylan, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. J.E.M. Wong-Cruz: None.