FDA Approves Type 2 Diabetes Treatment to Help Prevent Cardiovascular Risks

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. 

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. 

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. 

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; < 0.001 for noninferiority; = 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). 

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. 

The findings of the CANVAS Program were published the New England Journal of Medicine. 

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomized placebo-controlled trial 

Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population- based study 

Bariatric Surgery Reduces Macrovascular Risks in Obese Diabetes Patients 

Cardiovascular Risk Profile in Patients with Diabetes and Acromegaly or Cushing’s Disease – Analysis from the DPV Database 

Sources: NEJM, Janssen Pharmaceutical CompaniesMedscape Medical News