SGLT-2 inhibitor empagliflozin is first OAD to receive cardiovascular indication
Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, recently received the National Pharmaceutical Regulatory Agency’s approval for an update on its indication.
Originally, empagliflozin’s indication statement read: ‘Jardiance® (empagliflozin’s tradename) is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise.’ It is now approved for the treatment of adults with type 2 diabetes and established cardiovascular disease to reduce the risk of cardiovascular death. The additional cardiovascular (CV) indication follows the approval by the European Commission to the drug, for its effect on both blood sugar control and CV events in January 2018. Empagliflozin is the first SGLT2 inhibitor and the first oral antidiabetic agent to exhibit CV benefit in a clinical trial.
The trial in question is EMPA-REG OUTCOME® trial, which saw a patient pool of 7,020 patients. The primary outcome of the trial was death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke. The primary outcome was observed in 490 of 4,687 patients in the pooled empagliflozin group (10.5 percent). Meanwhile, the placebo group saw 282 of 2,333 patients experiencing the primary outcome (12.1 percent).
The researchers noted no significant difference between groups for the rates of myocardial infarction (MI) or stroke but noticed a significantly lower rate of death from CV causes in the empagliflozin group (3.7 percent vs 5.9 percent in the placebo group, 38 percent relative risk reduction).
Furthermore, the empagliflozin group experienced less hospitalization for heart failure (2.7 percent versus 4.1 percent in the placebo group, 35 percent relative risk reduction) and also a reduction in all-cause death (5.7 percent versus 8.3 percent in the placebo group, 32 percent relative risk reduction). [N Engl J Med 2015;373:2117–2128]
Speaking at a media event to highlight empagliflozin’s new indication, Professor Chee Kok Han, senior consultant cardiologist, University Malaya Medical Centre, said: “By extending the [empagliflozin] label, physicians are now able to provide a diabetes medication that offers a life-saving CV benefit to type 2 diabetes patients with established CV diseases.”
Also present at the event, Dr Zanariah Hussein, consultant endocrinologist, Hospital Putrajaya, said: “The prevalence of diabetes in Malaysia is alarmingly high and the number of people with type 2 diabetes has escalated to 20.8 percent in adults above the age of 30. Managing life with diabetes not only restrains people in their daily life, it also signifies an additional financial burden to the families of patients.”
Dr Chan Siew Pheng, senior consultant endocrinologist, noted that patients with type 2 diabetes are at higher risk of CV morbidity and death. They are also disproportionately affected by CV diseases such as stroke, heart failure and heart attacks. As such, the additional CV benefit of an oral antidiabetic (OAD) agent such as empagliflozin is greatly welcomed by the medical fraternity.
It is worth noting that patients on empagliflozin experienced slightly elevated rates of genital infection but experienced no increase in other adverse events. The increase in genital infection is a feature shared by all OAD agents in the SGLT2 inhibitor class as the drugs work by flushing out sugar through the urine. [Curr Drug Saf 2018 doi: 10.2174/1574886313666180226103408] Additionally, SGLT2-inhibitors are contraindicated in persons with kidney impairment, as the medication makes the user urinate more and thus, may further tax the diseased kidneys.