In this post hoc analysis of data from the CANVAS and CREDENCE trials, the authors sought to determine whether the effects of the SGLT2 inhibitor canagliflozin in people with type 2 diabetes were consistent across different race-specific BMI categories.
Data from 14 520 participants, randomised to canagliflozin or placebo, were evaluated. Overall, 64% had obesity at baseline, 28% were overweight and 8% were normal-weight or underweight. In the pooled cohort, the primary outcome of three-point major adverse cardiovascular events was reduced by 17% with canagliflozin, and this benefit was consistent across the three BMI classes, with hazard ratios ranging from 0.81 to 0.89 between the subgroups (P=0.76 for heterogeneity). Absolute risk reductions were also similar across the subgroups.
The effects of canagliflozin on chronic eGFR slope and urinary ACR were also consistent across the BMI subgroups, as was the safety profile of the agent. Perhaps unsurprisingly, the effects of canagliflozin on weight loss were greater in obese participants (mean reduction 2.31 kg) than in overweight (1.86 kg) and normal/underweight participants (1.40 kg). Small but significant differences in systolic blood pressure were also observed between the BMI subgroups, with reductions ranging from 3.48 mmHg in obese participants to 4.90 mmHg in normal/underweight participants.
People in different weight classes may have differences in body composition and organ metabolism, as well as differences in gastric emptying and permeability, which may affect drug absorption, metabolism and elimination. The present findings, although limited by the post hoc nature of the study, are reassuring that the effects of canagliflozin are consistent across different weight classes.
Attempts to achieve remission, or at least a substantial improvement in glycaemic control, should be the initial focus at type 2 diabetes diagnosis.
9 May 2024