Clinical outcomes with canagliflozin according to baseline body mass index: results from post hoc analyses of the CANVAS Program

Abstract

Aims Sodium glucose co‐transporter 2 (SGLT2) inhibitors reduce several cardiovascular risk factors, including plasma glucose, blood pressure, albuminuria and body weight. Long‐term treatment lowers risks of cardiovascular and renal events. The objective of this post hoc analysis was to determine the effects of canagliflozin treatment versus placebo on clinical outcomes in relation to body mass index (BMI). Materials and methods The CANVAS Program randomized 10 142 participants with type 2 diabetes to canagliflozin or placebo. These analyses tested the consistency of canagliflozin treatment effects across BMI levels for cardiovascular, renal, safety and body weight outcomes in three groups defined by baseline BMI: <25, 25‐<30 and ≥30 kg/m2. Results In total, 10 128 participants with baseline BMI measurements were included. There were 966 participants with BMI <25 kg/m2, 3153 with BMI 25‐<30 kg/m2 and 6009 with BMI ≥30 kg/m2. Mean percent body weight reduction with canagliflozin compared with placebo was greater at 12 months [−2.77% (95% confidence interval (CI): −2.95, ‐2.59)] than at 3 months [‐1.72% (95% CI: ‐1.83, ‐1.62)]. The hazard ratios (HRs) for canagliflozin compared with placebo control for the composite outcome of cardiovascular death, non‐fatal myocardial infarction or non‐fatal stroke were 1.03 (95% CI: 0.66, 1.59) in participants with BMI <25 kg/m2, 0.97 (0.76, 1.23) with BMI 25‐<30 kg/m2 and 0.79 (0.67, 0.93) with BMI ≥30 kg/m2 (P for heterogeneity = 0.55). The effects of canagliflozin on each component of the composite were also similar across BMI subgroups, as were effects on heart failure and renal outcomes (P for heterogeneity ≥0.19). The effects on safety outcomes were also broadly similar. Conclusions Canagliflozin improved cardiovascular and renal outcomes consistently across patients with a broad range of BMI levels.

What have we learned about renal protection from the cardiovascular outcome trials and observational analyses with SGLT2 inhibitors?

“…The effect of canagliflozin on the primary outcome was similar in patients with and without CKD at baseline. Similarly, relative effects on CV and renal outcomes did not differ across eGFR subgroups or across categories for body mass index . In the CANVAS Program cohort, Neuen et al have also reported that renal and CV outcome benefits of canagliflozin are generally consistent across levels of baseline albuminuria, with the exception that greater absolute renal composite risk reductions were detected in patients with severely increased albuminuria at baseline .…”

SGLT2 Inhibitors and the Clinical Implications of Associated Weight Loss in Type 2 Diabetes: A Narrative Review

“…A post hoc analysis [29] showed similar cardiorenal results between different baseline body mass index (BMI) groups. The authors acknowledged a substantial variation in weight change over time.…”

Cardiovascular outcome trials in obesity: A review

“…9 Abdominal obesity was significantly related to acute myocardial infarction (MI; HR [99% CI]: 1. 62 population attributable risk 20.1% for the top two tertiles vs. lowest tertile). 9 Waist circumference was shown to correlate with direct measurement of visceral adiposity 10 and is also an independent risk factor for CHD.…”

“…CV, cardiovascular; CVOT, cardiovascular outcomes trial; GLP-1RA, glucagon-like peptide-1 receptor agonist; HFpEF, heart failure with preserved ejection fraction; MACE, major adverse cardiovascular event; T2D, type 2 diabetescategory was associated with a high risk of CVD/hospitalization for heart failure. A subanalysis of the CANVAS programme, which tested the consistency of canagliflozin across baseline BMI categories of <25, 25 to <30 and ≥30 kg m −2 showed that there was no difference in treatment-related outcomes across the BMI levels 62.…”