Abstract
Objective: We aimed to evaluate the efficacy of canagliflozin for the treatment of specific cardiovascular and renal outcomes in Type 2 diabetes mellitus (T2DM) patients by means of a systematic review and meta-analysis. Methods: We performed comprehensive searches of PubMed, the Cochrane Library, and Embase for randomized, placebo-controlled trials of the treatment of T2DM with canagliflozin that were published to 28 September 2020. The cardiovascular outcomes recorded were cardiovascular mortality, heart failure, myocardial infarction, and stroke. The renal composite outcomes recorded were end-stage renal disease (ESRD), renal death. The data for the principal cardiovascular outcomes, ESRD, and renal death were pooled and expressed as Hazard ratios (HRs) with 95% confidence intervals (CIs). Two reviewers independently selected the trials and extracted the data. Results: We identified a total of 1,741 publications, leaving 96 for their titles, abstracts and full-text review. Of these, 10 trials met the inclusion criteria and were finally included in our meta-analysis. The meta-analysis showed that canagliflozin significantly reduced the risk of heart failure in T2DM by 36% (HR 0.64, 95% CI 0.53 to 0.77, p = 0.000). The effects of canagliflozin on non-fatal myocardial infarction or non-fatal stroke (HR 0.84, 95% CI: 0.76 to 0.93, p = 0.001), cardiovascular mortality (HR 0.84, 95% CI 0.72 to 0.97, p = 0.021), and myocardial infarction (HR 0.84, 95% CI 0.70 to 1.00, p = 0.045) in patients with T2DM were relatively small, reducing the risks by 16%. In addition, canagliflozin reduced the risk of stroke in T2DM patients by 13% (HR 0.87, 95% CI 0.71 to 1.06, p = 0.166). Moreover, canagliflozin significantly reduced the risk of the composite renal event of ESRD or renal death by 36% (HR 0.64, 95% CI 0.54 to 0.75, p = 0.000). Conclusion: This meta-analysis suggests that canagliflozin protects against cardiovascular and renal outcomes in patients with T2DM. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42020210315]
Highlights
Type 2 diabetes mellitus (T2DM) consists of a set of metabolic defects and is principally characterized by relative insulin deficiency resulting from a combination of pancreatic β-cell dysfunction and insulin resistance in target organs (Chatterjee et al, 2017)
We aimed to evaluate the efficacy of canagliflozin for the treatment of specific cardiovascular and renal outcomes in Type 2 diabetes mellitus (T2DM) patients by means of a systematic review and meta-analysis
The meta-analysis showed that canagliflozin significantly reduced the risk of heart failure in T2DM by 36% (HR 0.64, 95% confidence intervals (CIs) 0.53 to 0.77, p 0.000)
Summary
Type 2 diabetes mellitus (T2DM) consists of a set of metabolic defects and is principally characterized by relative insulin deficiency resulting from a combination of pancreatic β-cell dysfunction and insulin resistance in target organs (Chatterjee et al, 2017). The excess morbidity and mortality associated with T2DM are mainly the result of cardiovascular and renal complications (Braunwald, 2019). A previous retrospective cohort study showed that individuals with T2DM develop cardiovascular disease 14.6 years earlier than those without T2DM, and it tends to be more serious (Booth et al, 2006). Renal disease is another common complication of T2DM, and approximately 10% of the deaths of patients with T2DM are related to renal failure (Van Dieren et al, 2010). When selecting antidiabetic drugs for patients with T2DM, physicians should consider their efficacy for the prevention or treatment of cardiovascular and renal outcomes
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