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 an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included—279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (−0.90%) and weight (−4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (−0.35%) and weight (−2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.

Aim: This study aimed to evaluate the effectiveness and tolerability of intensifying the dose of canagliflozin from 100 mg/day (CANA100) to 300 mg/day (CANA300) in patients with type 2 diabetes (T2DM) and suboptimal metabolic control in a real-world setting. Methods: A multicenter observational study was conducted on adult patients with T2DM who initiated treatment with CANA100 and subsequently required intensification to CANA300. The primary outcome measures were changes in HbA1c and weight at 6 months after the switch and at the end of the follow-up period. Results: A total of 317 patients met the inclusion criteria (59.6% male, mean age 62.2 years, baseline HbA1c 7.55%, weight 88.6 kg, median duration of treatment with CANA100 9.9 months). Switching to CANA300 resulted in a significant reduction in HbA1c (6 months: −0.33%; last visit: −0.47%, both p < 0.0001) and weight (6 months: −1.8 kg; last visit: −2.9 kg, both p < 0.0001) over a median follow-up period of 20.8 months. The proportion of patients that achieved HbA1c < 7% increased from 26.7% with CANA100 to 51.6% with CANA300 (p < 0.0001). Among individuals with poor baseline glycemic control (HbA1c > 8%, mean 9.0%), HbA1c was significantly reduced by −1.24% (p < 0.0001). Furthermore, significant improvements were observed in fasting plasma glucose (FPG), blood pressure (BP), liver enzymes, and albuminuria. No unexpected adverse events were reported. Conclusions: Intensifying the treatment to CANA300 in a real-world setting resulted in further significant and clinically relevant reductions in FPG, HbA1c, weight, and BP in patients with T2DM. The switch was particularly effective in patients with higher baseline HbA1c levels.

The Real-WECAN study evaluated the real-life effectiveness and safety of canagliflozin 100 mg daily (initiated in SGLT-2 inhibitors naïve patients) and canagliflozin 300 mg daily (switching from canagliflozin 100 mg or other SGLT-2 inhibitors) in individuals with type 2 diabetes. The objectives of this sub-analysis were to estimate the eGFR slope over the follow-up period and to identify predictive factors of eGFR decline in a multiple linear regression analysis. A total of 583 patients (279 on canagliflozin 100 mg and 304 on canagliflozin 300 mg) were included, with median follow-up at 13 months. The patients had a mean age of 60.4 years, HbA1c of 7.76%, BMI of 34.7 kg/m2, eGFR below 60 mL/min/1.73 m2 8.6%, and urine albumin-to-creatinine ratio (UACR) above 30 mg/g 22.8%. eGFR decreased by −1.9 mL/min/1.73 m2 (p < 0.0001) by the end of the study. The mean eGFR slope during the maintenance phase was −0.16 mL/min/1.73 m2 per year. There were no significant differences between both doses of canagliflozin in the eGFR reduction or in the eGFR slope. The best predictive multivariate model of eGFR decline after canagliflozin therapy included age, hypertension, combined hyperlipidemia, heart failure, eGFR and severely increased albuminuria. All these variables except hypertension were independently associated with the outcome. In conclusion, in this real-world study, individuals with older age, combined hyperlipidemia, heart failure, higher eGFR and UACR > 300 mg/g showed a greater decline in their eGFR after canagliflozin treatment.

The aim of this multicentric retrospective study was to assess in a real-world setting kidney outcomes associated with canagliflozin 100 mg/d (CANA100), as add-on to the background antihyperglycemic therapy, and with the intensification of SGLT2 inhibitor (SGLT2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. 583 patients were included, 279 with CANA100 (eGFR 86.5 ml/min, eGFR&lt;60 12.3%, albuminuria &gt;30 mg/g 25.7%) and 304 with CANA 300 (eGFR 84.9 ml/min, eGFR&lt;60 9.1%, albuminuria &gt;30 mg/g 20.7%). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. The primary outcomes of the study were changes in eGFR, albuminuria and systolic BP (SBP) over the follow-up time. CANA100 was associated to significant reductions in eGFR (-2 ml/min) and SBP (-4.8 mmHg). In those patients with SBP&gt;140 mmHg, CANA 100 lowered SBP levels by 14.9 mmHg. No significant changes in albuminuria were observed. However, in the subset of patients with baseline albuminuria &gt;30 mg/gr, there was a significant decrease in median albuminuria. In the second cohort, patients with prior background SGLT2i therapy switched to CANA300. Significant reductions in eGFR (-1.8 ml/min), SBP (-3.2 mmHg), and median albuminuria (from 8.1 to 5.8 mg/g) were observed over the follow-up period. In those patients with SBP&gt;140 mmHg, CANA 300 lowered SBP levels by 15.9 mmHg. In the subset with baseline albuminuria &gt;30 mg/g, there was a significant decrease in median albuminuria. No significant changes in anti-hypertensive medications were observed over the follow-up. There was a low rate of adverse events related to volume depletion. In summary, CANA100 (as add-on therapy) and CANA300 (switching from CANA100 or other SGLT2i) significantly decreased SBP and modestly reduced eGFR. A significant reduction in albuminuria was observed with CANA300. 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.

There is a paucity of data evaluating the strategy of intensification of canagliflozin therapy by increasing the dose from canagliflozin 100 mg/d (CANA100) to canagliflozin 300 mg/d (CANA300), since all clinical trials compared both doses separately. The aim of this multicentric study was to assess in real life the effectiveness and tolerability of the intensification of canagliflozin to 300 mg/d in patients with T2DM and suboptimal metabolic control with CANA100. The primary outcome variables were changes in A1c and weight at the end of the follow-up. 317 patients met the inclusion criteria (age 62.2 years, A1c 7.55%, weight 88.6 kg). Median time of treatment with CANA300 was 20.8 months. Switching to CANA300 induced a significant decrease in A1c (-0.47%) and weight (-2.9 kg), both p&lt;0.0001. The percentage of patients with A1c &lt;7% increased significantly from 26.7% with CANA100 to 51.6% with CANA300 (p&lt;0.0001). In those individuals with poor glycemic control (A1c &gt;8%, mean 9.0%), A1c was significantly reduced by -1.24% (p&lt;0.0001). There were significant improvements in FPG (-14.8 mg/dl), SBP (-5.3 mmHg) and DBP (-3,1 mmHg), all p&lt;0.05. Serum liver enzymes and albuminuria also decreased significantly. Considering the entire treatment period (initial treatment with CANA100 and later switch to CANA300), with a median follow-up of 38.8 months, patients achieved a statistically significant overall reduction in A1c (-1.30%), weight (-5.8 kg), SBP (-9.6 mmHg) and DBP (-4.7 mmHg), all p&lt;0.0001. 7.9% of patients discontinued CANA300; the most frequent causes of withdrawals were genital mycotic infections (1.9%) and urinary tract infections (0.9%). In summary, intensification of canagliflozin therapy to CANA300 achieved further significant and clinically relevant reductions in A1c, weight, and BP in patients with T2DM. The effectiveness of the switch was particularly relevant in those patients with higher A1c levels. Disclosure J.J. Gorgojo-Martinez: Advisory Panel; AstraZeneca, Bayer Inc., Novo Nordisk. Research Support; Eli Lilly and Company, Mundipharma, Novo Nordisk. Speaker's Bureau; AstraZeneca, Boehringer Ingelheim Inc., Eli Lilly and Company, Mundipharma, Novo Nordisk, Amarin Corporation. P.J. Ferreira-Ocampo: None. A. Galdon-Sanz Pastor: None. J.J. Cárdenas-Salas: Speaker's Bureau; Novo Nordisk, Mundipharma, Lilly, AstraZeneca. Other Relationship; Mylan, Amgen Inc., Almirall, S.A. T. Antón-Bravo: Speaker's Bureau; Abbott Nutrition, AstraZeneca, Eli Lilly and Company. Advisory Panel; Fresenius Kabi. Speaker's Bureau; Novo Nordisk, Daiichi Sankyo. Advisory Panel; Sanofi. Other Relationship; Mundipharma. M. Brito: Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Mundipharma, Novo Nordisk, Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Almirall, S.A., Boehringer-Ingelheim, Esteve. Advisory Panel; Esteve, AstraZeneca. Research Support; Mundipharma. F. Almodovar-Ruiz: None. Funding Mundipharma International Limited