The findings of the CANagliflozin cardioVascular Assessment (CANVAS) study have been presented at the American Diabetes Association (ADA)’s 77th Scientific Sessions in San Diego, and they show that the drug has the ability to significantly reduce the risks for both cardiovascular disease (CVD) and renal disease.

Conducted by The George Institute for Global Health, CANVAS has major worldwide implications for the treatment of type 2 diabetes (T2D). In the United States, approximately 29 million people are living with diabetes; out of those, 8 million are undiagnosed, according to the Centers for Disease Control and Prevention (CDC) estimates.¹ Also according to the CDC’s data, at least 1 out of 3 people will develop T2D at some point in their lifetime.¹ The World Health Organization estimates that more than 422 people worldwide are already living with diabetes, and it projects that by 2030, diabetes will be the 7th leading cause of death worldwide.²

“Type 2 diabetes is growing rapidly all over the world, and we need drugs that not only deal with glucose levels, but also protect the many millions of people from the very real risks of stroke and heart attack,” Bruce Neal, professor at The George Institute for Global Health and lead investigator of CANVAS, said in a news release prior to the study results being presented at the ADA meeting. “Coronary heart disease is the biggest killer by far for people with type 2 diabetes. Our findings suggest that not only does canagliflozin significantly reduce the risk of heart disease, it also has many other benefits, too. We found it also reduced blood pressure and led to weight loss.”

The results of the study, which included more than 10,000 patients with T2D in 30 countries, were published simultaneously to their release at the ADA meeting in the New England Journal of Medicine. Those results showed that canagliflozin (Invokana®/Janssen Pharmaceuticals), which is in a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors, reduced the overall risk of CVD by 14% and reduced the risk of hospitalization for heart failure (HF) by 33%. Additionally, patients with diabetes were 40% less likely to suffer from serious kidney disease.

The median duration of the study population’s disease was ~14 years. Two thirds of the participants had CVD prior to entering the study.

“The important thing about this trial is that we showed clear protection against the primary outcome, which is vascular death, non-fatal stroke, and non-fatal heart attack, and we showed protection against poor kidney disease outcomes and hospitalization for heart failure,” Neal told MD Magazine® in an interview. “We also showed harm for the outcome of amputation, but, on balance, [taken] together, this is a really positive result for diabetes because the benefits are going to outweigh the harms. We’ve now got confirmation from canagliflozin…that what previously had been observed is reality.”

Based on the new data from CANVAS, the US Food and Drug Administration (FDA) on May 16 required canagliflozin to carry a Boxed Warning, the most prominent of its warnings, to describe the amputation risk.³ FDA issued the warning after the trial results showed that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with the placebo.

As a SGLT2 inhibitor, canagliflozin lowers blood sugar by blocking the reabsorption of glucose by triggering the kidneys to expel more glucose through urine output. The CANVAS study is important to diabetes researchers, clinicians, and patients because, according to American Heart Association estimates, adults with diabetes are 2 to 4 times more likely to die from heart disease than adults without the disease—at least 68% of patients with diabetes who are 65 or older die from some form of heart disease; and 16% die of stroke.⁴

Vlado Perkovic, the executive director of The George Institute Australia and co-author of the study, said in the news release that, “Both patients and physicians should be trememdously reassured by the results. What we have done is show that the earlier results were not just a one-off. This really is a game changer in the treatment of type 2 diabetes. It not only reduces the risk of heart disease, it also produces real protection against kidney decline, which affects many people with diabetes.”

Neal concluded his interview with MD Magazine® by saying, “We’re moving into this really exciting new era now where we’ve got medicines that treat people with diabetes and they not only lower their HbA1c but they also protect against the things that people with diabetes really care about.”

References

1. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: US Department of Health and Human Services; 2014. https://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html. Accessed June 12, 2017.

3. US Food and Drug Administration. Canagliflozin (Invokana, Invokamet): Drug Safety Communication - Increased Risk of Leg and Foot Amputations. https://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm558605.htm. Accessed June 12, 2017.

2. World Health Organization. Diabetes fact sheet. Reviewed November 2016. http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed June 12, 2017.4. American Heart Association. Cardiovascular Diseases & Diabetes. http://www.heart.org/HEARTORG/Conditions/More/Diabetes/WhyDiabetesMatters/Cardiovascular-Disease-Diabetes_UCM_313865_Article.jsp/#.WT7R9HeZPow. Accessed June 12, 2017.