The U.S. Food & Drug Administration (FDA) approved canagliflozin (Invokana) to reduce the risk of certain cardiovascular-related events, including heart attack or stroke, in adults with type 2 diabetes who have established cardiovascular disease.
Canagliflozin, a sodium–glucose cotransporter 2 inhibitor, reduces glycemia, blood pressure, body weight, and albuminuria in people with diabetes.
SGLT2i canagliflozin (Inkovana) become 3rd diabetes drug to receive an FDA indication for reducing MACE (MI. CVA or CV death, in T2D with established CVD https://t.co/W9RoveAYKz
— Thomas Dayspring (@Drlipid) November 1, 2018
Invokana is manufactured by the Janssen Pharmaceutical Companies of Johnson & Johnson. According to the company, the drug is the first oral diabetes medication indicated to reduce heart attack, stroke, and cardiovascular death. The FDA previously approved type 2 diabetes medication liraglutide with an indication of certain reduced cardiovascular risks, but liraglutide is an injection, not an oral medication.
— Am Soc Nephrology (@ASNKidney) November 1, 2018
The FDA’s approval follows the CANVAS (CANagliflozin cardioVascular Assessment Study) Program, two trials that evaluated cardiovascular, renal, and safety outcomes associated with canagliflozin. The trials included 10,142 type 2 diabetes patients (mean age, 63.3 years; 35.8% female; mean diabetes duration, 13.5 years; 65.6% cardiovascular disease history) with high cardiovascular risk. For a mean duration of 188.2 weeks, patients received either canagliflozin or placebo, with the primary outcome being death by cardiovascular causes, or nonfatal myocardial infarction or stroke.
ME: I still have concerns about canagliflozin re amputation risk and efficacy apparent only when combining two trials, thus prefer empagliflozin or liraglutide for pts with DM and CVD. FDA approves CV events indication for Invokana https://t.co/CzHXb0Tq4b
— Anand Rohatgi (@dranandrohatgi) November 1, 2018
Canagliflozin patients had a lower primary outcome rate than the placebo group (26.9 vs 31.5 participants per 1,000 patient-years; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.97; P < 0.001 for noninferiority; P = 0.02 for superiority). The study suggested that canagliflozin may reduce the progression of albuminuria (HR, 0.73; 95% CI, 0.67-0.79). It also indicated a 40% reduction in estimated glomerular filtration rate, and reduced the risk of need for renal-replacement therapy and death from renal causes (HR, 0.60; 95% CI, 0.47-0.77).
Read more about this agent here: https://t.co/YUcCnxOd63
— MDedge Cardiology (@MDedgeCardio) October 31, 2018
The most notable adverse effect was an increased amputation risk in canagliflozin patients compared with placebo patients (6.3 vs. 3.4 participants per 1,000 patient-years; HR, 1.97; 95% CI, 1.41-2.75), particularly at the level of the toe or metatarsal. At the time the study results were published, lead researcher Bruce Neal, PhD, of the George Institute for Global Health in Australia, told MedPage Today the link between canagliflozin and increased amputation risk was not clear, but that patients at an increased risk for amputation were those who had an amputation previously as well as patients with severe peripheral vascular disease or chronic foot ulcers. “Unless there’s a very good reason, you’re not going to want to put [them] on canagliflozin,” said Dr. Neal.
#Canagliflozin is approved for glucose lowering in #type2diabetes and confers #CV & renal benefits. Does baseline renal function matter? What we know from the #CANVAS program data: https://t.co/HbIPSU25Tu @brendonneuen @VladoPerkovic @georgeinstitute pic.twitter.com/ldwegwrElp
— Circulation (@CircAHA) October 10, 2018
The findings of the CANVAS Program were published the New England Journal of Medicine.