Empagliflozin

Empagliflozin, sold under the brand name Jardiance among others, is a medication used together with diet and exercise to treat type 2 diabetes. It can be prescribed instead of metformin and has benefits over sulfonylureas. It may be used together with other medications such as metformin or insulin. It is not recommended for type 1 diabetes. It is taken by mouth. In view of recent trial evidence, it is expected to soon receive licence to be used for patients with heart failure, irrespective of diabetic status. 
Common side effects include urinary tract infections, fungal infections of the groin, and joint pains. Rarer but more serious side effects include a skin infection of the groin called Fournier's gangrene and a form of diabetic ketoacidosis with normal blood sugar levels. Use in pregnancy and breastfeeding is not recommended. Use is not recommended in those with significant kidney disease, though it may help slow the progression of mild kidney problems. Empagliflozin is an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), and works by increasing sugar lost in the urine.
Empagliflozin was approved for medical use in the United States and in the European Union in 2014. In 2017, it was the 228th most commonly prescribed medication in the United States, with more than two million prescriptions.
Medical uses.
Type 2 diabetes.
Empagliflozin is used in combination with proper diet and exercise to help people with type 2 diabetes lower their blood sugar levels. It can be used alongside other medications for type 2 diabetes such as metformin, sulfonylureas, and insulin. When compared to a placebo, empagliflozin led to a drop of 0.7% in hemoglobin A1c, a long-term marker of blood glucose levels.
Weight and blood pressure.
Empagliflozin causes moderate reductions in blood pressure and body weight. These effects are likely due to the excretion of glucose in the urine and a slight increase in urinary sodium excretion. In clinical trials, patients taking empagliflozin lost an average of 2% of their baseline body weight. A higher percentage of people taking empagliflozin achieved weight loss greater than 5% from their baseline. The medication reduced systolic blood pressure by 3 to 5 millimeters of mercury (mmHg). The effects on blood pressure and body weight are generally viewed as favorable, as many patients with type 2 diabetes have high blood pressure or are overweight or obese.
Heart kidney disease.
SGLT2 inhibitors, including empagliflozin, appear to reduce the likelihood of hospitalization for heart failure or progression of chronic kidney disease in persons with type 2 diabetes. Empagliflozin may reduce the likelihood of death due to cardiovascular causes in people with type 2 diabetes who have known cardiovascular disease. One concern regarding the trial on which these claims are based is that the different arms received different amounts of other medications; thus, the reduced risk cannot necessarily be attributed to empaglifozin. In some countries it has also been approved to reduce the risk of death from cardiovascular causes in people with type 2 diabetes and heart disease.
Treatment guidelines.
Guidelines by the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) recommend SGLT-2 inhibitors like empagliflozin as second-line medications after metformin for type 2 diabetes in people with heart failure or chronic kidney disease. For type 2 diabetes with established cardiovascular disease, the guidelines recommend either a SGLT-2 inhibitor or a GLP-1 agonist as second-line medications after metformin. In all other type 2 diabetes cases, SGLT-2 inhibitors like empagliflozin can be appropriate second-line options if blood glucose control or weight loss are treatment priorities. They are less appropriate if cost is a major factor.
In the United Kingdom empagliflozin is typically only recommended together with metformin if a sulfonylurea cannot be taken.
Type 1 diabetes.
Empagliflozin is not recommended for type 1 diabetes. One trial studied its use in addition to insulin in people with type 1 diabetes. The medications delivered modest improvements in blood glucose control and body weight but were associated with an increased risk of diabetic ketoacidosis, a dangerous complication of diabetes. Empagliflozin is not approved by the U.S. Food and Drug Administration (FDA) for use in type 1 diabetes.
Mechanism of action.
Empagliflozin is an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), which is found almost exclusively in the proximal tubules of nephronic components in the kidneys. SGLT-2 accounts for about 90 percent of glucose reabsorption into the blood. Blocking SGLT-2 reduces blood glucose by blocking glucose reabsorption in the kidney and thereby excreting glucose (i.e., blood sugar) via the urine.
History.
It was developed by Boehringer Ingelheim and Eli Lilly and Company. It is also available as the combination empagliflozin/linagliptin, empagliflozin/metformin, or empagliflozin/linagliptin/metformin.
Regulatory status.
As of May 2013, Boehringer and Lilly had submitted applications for marketing approval to the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). The drug was approved in Europe in May 2014, and was approved by the FDA in August 2014. The FDA required four postmarketing studies: a cardiovascular outcomes trial, two studies in children, and a toxicity study in animals related to the pediatric trials.