Comparing the effects of canagliflozin vs glimepiride by body mass index in patients with type 2 diabetes and chronic heart failure: a sub-analysis of the CANDLE trial

Background: It is not known if presence or absence of obesity influence the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). We present results of a 24-week comparative study of the effects of the SGLT2 inhibitor canagliflozin vs the sulfonylurea glimepiride, by baseline body mass index (BMI), in patients with type 2 diabetes and chronic heart failure. Methods: : We conducted a post hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized controlled trial. This sub-analysis evaluated changes at 24 weeks in NT-proBNP, BMI, and other laboratory parameters, according to the subgroups stratified by baseline BMI ≥25 kg/m 2 defined as obesity vs BMI <25 kg/m 2 defined as normal. Results: : A group ratio (canagliflozin versus glimepiride) of proportional changes in the geometric means of NT-proBNP was 0.99 (95% confidence interval [CI] 0.84 to 1.18, P =0.940) for the subgroup with baseline BMI ≥25 kg/m 2 and 0.85 (95% CI 0.71 to 1.02, P =0.075) for the subgroup with baseline BMI <25 kg/m 2 , respectively. Although the group ratio for the subgroup with baseline BMI <25 kg/m 2 was smaller than that for the subgroup with baseline BMI ≥25 kg/m 2 , there was no statistical difference by baseline BMI subgroups ( P for interaction=0.222). When baseline BMI was modeled as a continuous variable, results for patients with BMI <30 kg/m 2 showed a slightly smaller increase in NT-proBNP in the canagliflozin group vs the glimepiride group; that difference was not seen among patients with BMI ≥30 kg/m 2 . Irrespective of obesity, the canagliflozin group was associated with significant reduction of BMI compared to the glimepiride group. Conclusion: Although there was no significant difference in the effects of 24-week of canagliflozin treatment, relative to glimepiride, on NT-proBNP concentrations irrespective of baseline obesity, the canagliflozin treatment showed a trend toward lower NT-proBNP levels in patients across BMI <30 kg/m 2 . This suggests that baseline BMI levels affect the effect of SGLT2 inhibitor treatment on NT-proBNP concentrations. Further studies are needed to assess the association between clinical effects of SGLT2 inhibitor and obesity. UMIN clinical trial registration number (http://www.umin.ac.jp/): UMIN000017669