reductions across multiple endpoints may impact your patients’ care1

Primary endpoint: Canagliflozin + metformin demonstrated significantly greater reductions in A1C* vs placebo + metformin at 26 weeks1

Adjusted mean change in A1C from baseline:

  • Placebo + metformin (n=181; mean baseline: 8.0%): –0.17%
  • Canagliflozin 100 mg + metformin (n=365; mean baseline: 7.9%): –0.79%
    • Difference from placebo: –0.62% (95% Cl: –0.76, –0.48); P<0.001
  • Canagliflozin 300 mg + metformin (n=360; mean baseline: 8.0%): –0.94%
    • Difference from placebo: –0.77% (95% Cl: –0.91, –0.64); P<0.001

In this study of patients with type 2 diabetes and inadequate glycemic control on metformin (≥2000 mg/day, or ≥1500 mg/day if higher dose not tolerated), canagliflozin and metformin, and sitagliptin and metformin, were coadministered as separate tablets.1

canagliflozin + metformin vs sitagliptin 100 mg + metformin at 52 weeks across multiple secondary endpoints1

Reductions with INVOKAMET vs. Janumet

*The primary endpoint was the change in A1C vs placebo from baseline through week 26; change in A1C vs sitagliptin was a prespecified secondary endpoint at week 52.1

Assuming a group difference of 0.5% (5.5 mmol/mol) between canagliflozin and placebo and a common SD of 1.0% (10.9 mmol/mol) for change in A1C, and using a 2-sample, 2-sided t test with a type 1 error rate of 0.05, an estimated 86 participants per group were required to achieve 90% power to demonstrate statistical superiority of canagliflozin to placebo.1

Canagliflozin is not indicated for weight loss or as an antihypertensive treatment.

Secondary endpoint: adjusted mean change in A1C from baseline at 52 weeks (%)1

A1C reductions with canagliflozin + metformin vs. sitagliptin + metformin

 

  • Canagliflozin 100 mg + metformin difference from sitagliptin 100 mg + metformin: 0.00% (95% CI: –0.12, 0.12)
  • Canagliflozin 300 mg + metformin difference from sitagliptin 100 mg + metformin: –0.15% (95% CI: –0.27, –0.03)

Secondary endpoint: adjusted mean change in body weight from baseline at 52 weeks (%)1

Body weight reductions with canagliflozin + metformin vs. sitagliptin + metformin

Systolic blood pressure reductions with canagliflozin + metformin vs. sitagliptin + metformin

  • Canagliflozin 100 mg + metformin difference from sitagliptin 100 mg + metformin: –2.4% (95% CI: –3.0, –1.8; P<0.001)
  • Canagliflozin 300 mg + metformin difference from sitagliptin 100 mg + metformin: –2.9% (95% CI: –3.4, –2.3; P<0.001)

Canagliflozin is not indicated for weight loss.

Secondary endpoint: adjusted mean change in systolic BP from baseline at 52 weeks (mm Hg)1

Systolic blood pressure reductions with canagliflozin + metformin vs. sitagliptin + metformin

  • Canagliflozin 100 mg + metformin difference from sitagliptin 100 mg + metformin: –2.9 mm Hg (95% CI: –4.5, –1.3; P<0.001)
  • Canagliflozin 300 mg + metformin difference from sitagliptin 100 mg + metformin: –4.0 mm Hg (95% CI: –5.6, –2.4; P<0.001)

Canagliflozin is not indicated as an antihypertensive treatment.

Dual therapy vs placebo + metformin at 26 weeks and vs sitagliptin + metformin at 52 weeks (Lavalle-González et al)

A double-blind, placebo- and active-controlled study of 1284 patients who were inadequately controlled on metformin alone. Study consisted of a 2-week, single-blind, placebo run-in period, a 26-week, placebo- and active-controlled treatment period (period 1) followed by a 26-week, active-controlled treatment period (period 2). Patients were randomized to the addition of canagliflozin 100 mg, canagliflozin 300 mg, sitagliptin 100 mg, or placebo. The primary endpoint was the change in A1C from baseline through week 26; change in A1C from baseline through week 52 was a prespecified secondary endpoint.1

Reference: 1. Lavalle-González FJ, Januszewicz A, Davidson J, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013;56:2582-2592. Supplemental tables available at: http://link.springer.com/article/10.1007%2Fs00125-013-3039-1. Accessed May 16, 2018.