impact long-term patient outlook with consistent A1C, body weight, and systolic blood pressure (BP) reductions1

The CANVAS Program, the largest and longest completed outcomes trial of any SGLT2 inhibitor to date, included a broad range of high-risk patients who had established cardiovascular disease (CVD) or were at risk for CVD1,2

A1C reductions for up to 6.5 years1

  • On a background of standard of care, the use of other antihyperglycemic agents during follow-up was 9.3% lower in the INVOKANA® group than in the placebo group (95% CI: –11.0, –7.6)1
  • After week 18, glycemic goals were based upon standard diabetes guidance and adjustments to treatment were individualized for the patient3
  • Use of background therapy for glycemic management and other control of risk factors were guided by best practice according to local guidelines1

Adjusted mean change in A1C from baseline vs placebo (on a background of standard of care) over 338 weeks1:

Adjusted mean difference in A1C from baseline vs. placebo with INVOKANA® (canagliflozin)

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

The CANVAS program was not designed to evaluate the effect of INVOKANA® vs Placebo on A1C, Body Weight, and Systolic Blood Pressure over 338 weeks.

SGLT2=sodium-glucose co-transporter 2.

 

Adjusted mean difference from placebo in body weight from baseline over 338 weeks (lb)1

Adjusted mean difference from placebo in body weight from baseline with INVOKANA® (canagliflozin)

Body and weight baby

  • INVOKANA® difference from placebo (on a background of standard of care): –3.53 lb (–1.60 kg; 95% CI: –1.70, –1.51; P<0.001)

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

The CANVAS program was not designed to evaluate the effect of INVOKANA® vs Placebo on A1C, Body Weight, and Systolic Blood Pressure over 338 weeks.

SGLT2=sodium-glucose co-transporter 2.

Adjusted mean difference from placebo in systolic BP from baseline over 338 weeks (mm Hg)1

Adjusted mean difference from placebo in systolic BP from baseline with INVOKANA® (canagliflozin)

  • INVOKANA® difference from placebo (on a background of standard of care): –3.93 mm Hg (95% CI: –4.30, –3.56; P<0.001)

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

The CANVAS program was not designed to evaluate the effect of INVOKANA® vs Placebo on A1C, Body Weight, and Systolic Blood Pressure over 338 weeks.

SGLT2=sodium-glucose co-transporter 2.

 

patient population in the CANVAS Program1

The CANVAS Program involved 2 trials (CANVAS and CANVAS-R) with a total of 10,142 patients with type 2 diabetes:

  • 65.6% of patients were ≥30 years of age with a history of symptomatic atherosclerotic cardiovascular disease
  • 34.4% of patients were ≥50 years of age with ≥2 risk factors* for cardiovascular disease

*Duration of diabetes ≥10 years, systolic BP >140 mm Hg while they were receiving ≥1 antihypertensive agents, currently smoking, microalbuminuria or macroalbuminuria, or HDL cholesterol level <1 mmol/L (38.7 mg/dL).

background therapies in the CANVAS Program1

  • The use of other antihyperglycemic agents during follow-up was 9.3% lower in the INVOKANA® group than in the placebo group (95% CI: –11.0, –7.6)

Baseline background therapies in the CANVAS Program (N=10,142)1,4

Antihyperglycemic agents
Insulin 50.2%
Sulfonylurea 43.0%
Metformin 77.2%
GLP1 receptor agonist 4.0%
DPP4 inhibitor 12.4%
Cardioprotective agents
Statin 74.9%
Antithrombotic 73.6%
RAAS inhibitor 80.0%
Beta blocker 53.5%
Diuretic 44.3%
Antihypertensive agents
ACE inhibitor/ARB 80.0%

One patient was randomized at 2 different sites and only the first randomization is included in the ITT analysis set.

ACE=angiotensin-converting enzyme; ARB=angiotensin receptor blocker; DPP4=dipeptidyl peptidase-4; GLP1=glucagon-like peptide-1; ITT=intent-to-treat; RAAS=renin-angiotensin-aldosterone system.

Long-term cardiovascular outcomes trial at 338 weeks (Neal et al)

The CANVAS Program involved 2 trials (CANVAS and CANVAS-R) with a total of 10,142 men and women with type 2 diabetes. Of the participants, 96.0% completed the trial and vital status was confirmed for 99.6%. The mean follow-up for the CANVAS Program was 188.2 weeks, while the length of follow-up was 295.9 weeks and 108.0 weeks in the CANVAS and CANVAS-R trials, respectively. Participants were either ≥30 years of age with a history of symptomatic atherosclerotic cardiovascular disease or ≥50 years of age with ≥2 risk factors* for cardiovascular disease. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes planned for sequential conditional hypothesis testing were death from any cause, death from cardiovascular causes, progression of albuminuria, and the composite of death from cardiovascular causes and hospitalization for heart failure.1

*Duration of diabetes ≥10 years, systolic blood pressure >140 mm Hg while they were receiving ≥1 antihypertensive agents, currently smoking, microalbuminuria or macroalbuminuria, or HDL cholesterol level <1 mmol/L (38.7 mg/dL).

References: 1. Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657. Supplementary appendix available at: doi:10.1056/NEJMoa1611925. 2. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. 3. Neal B, Perkovic V, de Zeeuw D, et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—a randomized placebo-controlled trial. Am Heart J. 2013;166(2):217-223.e11. 4. Data on file. Janssen Pharmaceuticals, Inc., Titusville, NJ.