Effects of canagliflozin on HbA(1c) and changes in antihyperglycaemic agents in the CANVAS Programme

Background and aims

Canagliflozin (CANA) improved glycaemic control by reducing HbA1c in a broad range of patients with type 2 diabetes (T2D) across its clinical trial program. This analysis examines the effects of CANA on HbA1c and changes in use of antihyperglycaemic agents (AHAs) in patients with high cardiovascular (CV) risk in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program.

Materials and methods

The CANVAS Program randomly assigned 10,142 participants with T2D and established CV disease or ≥2 CV risk factors to treatment with CANA or placebo (PBO). Least squares (LS) mean changes from baseline HbA1c and initiation of new AHAs were analysed in the on-treatment population (patients receiving CANA/PBO or within 30 days after discontinuation; n = 10,134).

Results

From a baseline mean HbA1c of 8.2%, the maximum difference between CANA and PBO (PBO-subtracted difference [95% CI]:–0.64% [–0.68, –0.61]; mean 8.1% vs 7.5%) was observed at Week 26. After Week 26, the curves began to converge, reaching a minimum difference between CANA and PBO of –0.23% (95% CI: –0.33, –0.14; 8.2% vs 8.0%) at Week 286. At the end of the study (Week 338), the mean difference HbA1c with CANA versus PBO was –0.24% (95% CI: –0.37, –0.10; 8.1% vs 7.9%), with a mean reduction of –0.58% (95% CI: –0.61, –0.56) with CANA versus PBO over the entire follow-up period. Discontinuation from study drug was about the same in both treatment groups during the first year of the study; after Week 52, more patients discontinued PBO versus CANA.

At baseline, the treatment groups were well-balanced with respect to AHA use. Almost all patients (98.6%) were being treated with ≥1 AHA at baseline (18.7% on 1 AHA, 43.6% on 2 AHAs, and 36.3% on ≥3 AHAs). The most common AHAs at baseline were biguanides (77.2%), insulin (50.3%), and sulfonylureas (43.0%). Over the course of the study, approximately 22% of patients initiated new AHAs during treatment with study drug, with DPP-4 inhibitors and insulin being the most common newly initiated AHAs (Table). A higher proportion of PBO-treated patients initiated AHA therapy across all classes, including insulin. Through the first and second years of the study, patients in the PBO group initiated new AHAs approximately twice as often as CANA-treated patients (first year: 6.3% and 14.7% with CANA and PBO; first 2 years: 11.3% and 22.9% with CANA and PBO).

Conclusion

In the CANVAS Program, patients treated with CANA had greater reductions in HbA1c compared with patients treated with PBO. After 52 weeks of treatment, the difference in HbA1c between the CANA and PBO groups began to decrease likely due to the joint effects of discontinuation of randomized therapy and a higher rate of initiating new AHA therapies in the PBO group.