Effects of canagliflozin are mostly observed at first follow-up, within 6 months of commencement: results for the ABCD canagliflozin audit

Introduction:  Canagliflozin was initially approved for use in the UK in March 2013. Randomised control trial evidence has demonstrated multiple beneficial effects. Many of these are present at initial follow-up and within 26 weeks of randomised control trial data. Our aim was to assess whether the beneficial effects of canagliflozin on multiple clinical and biochemical parameters occurred prior to first follow-up and, if so, whether these continued to improve or simply persisted at second follow-up. Methods:  Data were extracted from the ABCD nationwide canagliflozin audit to include a minimum dataset of a baseline value and one (or two) follow-ups for each value. Results:  A total of 1,214 patient datasets were identified and used in the analysis: mean±SD age 60.1±10.6 years; median duration of diabetes 8 (IQR 2.4–12.6 years); baseline HbA 1c  75.1±17.4 mmol/mol (9.0±1.59%) and weight 97.8±22.0 kg. 68.3% of the patients were Caucasian where this was known (n=183). At first follow-up (median 0.7 years) from baseline: change in HbA 1c  −9.3 mmol/mol (95% CI −8.2 to −10.4; p<0.0001), weight −2.3 kg (95% CI −1.9 to −2.5; p<0.0001); BMI −0.7 kg/m 2  (95% CI −0.6 to −0.8; p<0.0001); alanine aminotransferase −2 U/L (95% CI −1.3 to −2.7; p<0.0001); eGFR −0.9 mL/min/1.73 m 2  (95% CI −0.4 to −1.4; p<0.001); systolic blood pressure (BP) −2.6 mmHg (95% CI −1.6 to −3.5; p<0.0001) and diastolic BP −0.9 mmHg (95% CI −0.2 to −1.6; p<0.001). Significant differences persisted comparing second follow-up (median 1.2 years) to baseline, but no further significant changes were noted between first follow-up and second follow-up other than in weight and BMI with further change in weight −0.65 kg (95% CI −0.2 to −1.1; p=0.047). Conclusion:  The improvements following canagliflozin in this real-world cohort seem to occur within the first 0.7 years of treatment, which is similar to randomised controlled trial data. These improvements seem to be maintained over the next 6 months, with significant further weight loss occurring between 0.7 years and 1.2 years, although the mechanism of this is unclear and might be due to confounders. More evidence on this point is needed.