Empagliflozin (Jardiance), approved in 2014 to treat adults with type 2 diabetes, is now approved to reduce the risk of cardiovascular death in adult patients with type 2 diabetes who have established cardiovascular disease. Approval was based on findings from a randomized, double-blind, multicenter, multinational, parallel-group postmarketing trial of more than 7,000 patients, which showed that empagliflozin significantly reduced the risk of cardiovascular death when added to standard-of-care therapies for diabetes and atherosclerotic cardiovascular disease. The risk of nonfatal myocardial infarction or stroke was not affected by empagliflozin therapy.
Empagliflozin belongs to the class of drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 is the primary transporter allowing for reabsorption of glucose in the kidneys. Patients with type 2 diabetes tend to have a variation in SGLT2 that causes them to reabsorb more glucose than normal. SGLT2 inhibitors such as empagliflozin prevent renal reabsorption of filtered glucose so that more glucose is excreted in the urine. Excess glucose in the urine may account for the increased risk of urinary tract infections with empagliflozin therapy.
In addition to the new indication, empagliflozin's labeling contains two new warnings and precautions. The first highlights a risk of ketoacidosis with empagliflozin use. The Food and Drug Administration has received postmarketing surveillance reports of patients developing ketoacidosis while taking SGLT2 inhibitors, including empagliflozin. Some patients who developed ketoacidosis while using empagliflozin died. Identifying patients with ketoacidosis caused by empagliflozin can be difficult, because in these cases, unlike in most cases of ketoacidosis, blood glucose levels may not be significantly elevated. Moreover, patients with ketoacidosis from empagliflozin may have symptoms indicating dehydration and severe metabolic acidosis (such as nausea, vomiting, abdominal pain, malaise, and shortness of breath) rather than ketoacidosis. The revised empagliflozin label warns that in some patients receiving empagliflozin, risk factors for ketoacidosis (such as reduction in insulin dose, acute febrile illness, reduced caloric intake due to illness or surgery, pancreatic disorders suggesting insulin deficiency, and alcohol abuse) do contribute to its development. Empagliflozin is not approved for use in patients with type 1 diabetes or for the treatment of ketoacidosis. Nurses and other health care providers should consider the possibility of ketoacidosis if a patient taking empagliflozin presents with signs and symptoms of dehydration and metabolic acidosis. Treatment for ketoacidosis (insulin, fluid, and carbohydrate replacement) should be implemented as quickly as possible in these patients to prevent death.
The second warning and precaution added to empagliflozin's labeling concerns the risk of acute kidney injury and impaired renal function. Damage to the kidney is likely related to the decrease in intravascular volume that occurs with SGLT2 inhibitors such as empagliflozin. Empagliflozin increases serum creatinine and decreases the estimated glomerular filtration rate (eGFR). To decrease the risk of acute kidney injury or impairment of renal function in patients taking empagliflozin, patients should be assessed for factors that may predispose them to these adverse effects prior to initiating empagliflozin treatment. These risk factors include hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant use of other medications that can negatively affect kidney function (such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and nonsteroidal antiinflammatory drugs).
Empagliflozin may need to be temporarily withheld if the patient is not currently eating (because of acute illness, for example) or has lost body fluids (from gastrointestinal illness or excessive heat exposure, for example). If patients demonstrate signs or symptoms of acute kidney injury, empagliflozin therapy should be stopped and the acute kidney injury treated. The eGFR should be assessed at baseline prior to therapy and periodically during therapy. Empagliflozin is not recommended when a patient's eGFR is persistently less than 45 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2. For complete prescribing information for empagliflozin, see http://bit.ly/2jOxCAr.