Abstract
BackgroundTreatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications. The sodium glucose co-transporter 2 inhibitor, canagliflozin, has been shown to improve glycaemic control and reduce body weight and blood pressure (BP) with a favourable tolerability profile in a broad range of patients with T2DM. This post hoc analysis assessed the efficacy and safety of canagliflozin in patients with T2DM based on CV disease history or CV risk factors.MethodsAnalyses were based on pooled data from four 26-week, placebo-controlled, Phase 3 studies that evaluated canagliflozin 100 and 300 mg in patients with T2DM (N = 2313; mean HbA1c, 8.0%; body weight, 89 kg; systolic BP, 128 mmHg). Changes from baseline to week 26 in HbA1c, body weight, and systolic BP were assessed based on history of CV disease, history of hypertension, baseline statin use, and number of CV risk factors. Safety was assessed based on adverse event (AE) reports.ResultsAt week 26, both canagliflozin doses lowered HbA1c, body weight, and systolic BP compared with placebo in patients with and without CV disease history or risk factors. Placebo-subtracted HbA1c reductions with canagliflozin 100 and 300 mg were similar in patients with a history of CV disease (−0.95 and −1.07%) versus no history of CV disease (−0.71 and −0.90%), history of hypertension (−0.72 and −0.89%) versus no history of hypertension (−0.73 and −0.95%), baseline statin use (−0.77 and −0.99%) versus no statin use (−0.69 and −0.85%), and 0–1 CV risk factor (−0.72 and −0.87%) versus ≥2 CV risk factors (−0.74 and −1.02%). Similar body weight and systolic BP reductions were seen with canagliflozin versus placebo across subgroups. The incidence of AEs, AEs leading to discontinuation, and serious AEs was similar across subgroups.ConclusionsThe efficacy and safety of canagliflozin were generally consistent across subgroups of patients with T2DM and varying degrees of CV disease history or risk factors.Trial registration numbers and dates ClinicalTrials.gov: NCT01081834, 4 March 2010; NCT01106625, 1 April 2010; NCT01106677, 1 April 2010; NCT01106690, 1 April 2010
Highlights
Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications
These studies included evaluation of canagliflozin compared with placebo as monotherapy in patients with T2DM inadequately controlled with diet and exercise (ClinicalTrials.gov Identifier: NCT01081834) [15], and as combination therapy in patients on background metformin (NCT01106677) [16], metformin plus sulphonylurea (NCT01106625) [17], and metformin plus pioglitazone (NCT01106690) [18]
The high glycaemic subset (HbA1c >10 and ≤12.0%) of the monotherapy study [15] was not placebo controlled, and the sitagliptin arm of the add-on to metformin study [16] was not prespecified for efficacy comparisons versus canagliflozin at week 26; these populations were excluded from the analysis
Summary
Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications. The sodium glucose co-transporter 2 inhibitor, canagliflozin, has been shown to improve glycaemic control and reduce body weight and blood pressure (BP) with a favourable tolerability profile in a broad range of patients with T2DM This post hoc analysis assessed the efficacy and safety of canagliflozin in patients with T2DM based on CV disease history or CV risk factors. Other major contributors to increased CV risk in patients with T2DM include comorbid conditions such as hypertension and dyslipidaemia [5, 6] The presence of these comorbid conditions and the associated requirements for concomitant medication use can present significant clinical challenges in the treatment of patients with T2DM and a history of CV disease or CV risk factors [7, 8]. There remains a need for antihyperglycaemic agents (AHAs) that are efficacious and well tolerated in people with T2DM and CV disease history/risk factors; ideally, such medications would provide improved glycaemic control and favourable effects on CV risk factors such as body weight, hypertension, and dyslipidaemia
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