Empagliflozin, sold under the brand name Jardiance among others, is an

antidiabetic medication Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are thus ...

used to improve glucose control in people with type2 diabetes, to reduce the risk of cardiovascular death in adults with type2 diabetes and established cardiovascular disease, to reduce the risk of death and hospitalization in people with heart failure and low or preserved ejection fraction, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults. It can be prescribed instead of

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

and has benefits over

sulfonylureas Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the bet ...

. It may be used together with other medications such as metformin or

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

. It is not recommended for

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Common side effects include

urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

fungal infection Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common ti ...

s of the groin, and joint pains. Rarer but more serious side effects include a skin infection of the

groin In human anatomy, the groin (the adjective is ''inguinal'', as in inguinal canal) is the junctional area (also known as the inguinal region) between the abdomen and the thigh on either side of the pubic bone. This is also known as the medial comp ...

called

Fournier's gangrene Fournier gangrene is a type of necrotizing fasciitis or gangrene affecting the external genitalia or perineum. It commonly occurs in older men, but it can also occur in women and children. It is more likely to occur in diabetics, alcoholics, or th ...

and a form of

diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of ...

with normal blood sugar levels. Use in pregnancy and breastfeeding is not recommended. Use is not recommended in those with significant

kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...

, 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 Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

. Empagliflozin was approved for medical use in the United States and in the European Union in 2014. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. In 2020, it was the 102nd most commonly prescribed medication in the United States, with more than 6million prescriptions. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Medical uses

Type 2 diabetes

Empagliflozin is used in combination with proper diet and exercise to help people with type2 diabetes lower their blood sugar levels. It can be used alongside other medications for type2 diabetes such as

, and

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 Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...

excretion. In clinical trials, patients taking empagliflozin lost an average of 2% of their baseline

body weight Human body weight is a person's mass or weight. Strictly speaking, body weight is the measurement of weight without items located on the person. Practically though, body weight may be measured with clothes on, but without shoes or heavy accessor ...

. 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 5millimeters of mercury (mmHg). The effects on blood pressure and body weight are generally viewed as favorable, as many patients with type2 diabetes have high blood pressure or are overweight or obese.

Heart and kidney disease

Empagliflozin appears to reduce the likelihood of hospitalization for

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

or progression of

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

in people with type2 diabetes. Empagliflozin may reduce the likelihood of death due to cardiovascular causes in people with type2 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 type2 diabetes and

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

Treatment guidelines

Guidelines by the

American Diabetes Association The American Diabetes Association (ADA) is a United States-based nonprofit that seeks to educate the public about diabetes and to help those affected by it through funding research to manage, cure and prevent diabetes (including type 1 diabetes, ...

(ADA) and

European Association for the Study of Diabetes The European Association for the Study of Diabetes (EASD) is a scientific association founded in Montecatini Terme, Italy in 1965 with Joseph Hoet as Founding President. The aims of the association are to encourage and support research in the fiel ...

(EASD) recommend SGLT-2 inhibitors like empagliflozin as second-line medications after metformin for type2 diabetes in people with heart failure or chronic kidney disease. For type2 diabetes with established cardiovascular disease, the guidelines recommend either a SGLT-2 inhibitor or a

GLP-1 agonist Glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists (GLP-1-RA) or incretin mimetics, are agonists of the GLP-1 receptor. This class of medications is used for the treatment of type 2 diabetes Some drugs are also approve ...

as second-line medications after metformin. In all other type2 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 UK, empagliflozin is typically only recommended together with

if a

sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...

cannot be taken.

Type 1 diabetes

Empagliflozin is not recommended for

. One trial studied its use in addition to insulin in people with type1 diabetes. The medications delivered modest improvements in blood glucose control and body weight but were associated with an increased risk of

, a dangerous complication of diabetes. Empagliflozin is not approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) for use in type1 diabetes.

Contraindications

* History of a severe allergic reaction to empagliflozin *

End-stage kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...

Diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of ...

Side effects

Common

* Empagliflozin increases the risk of genital fungal infections. The risk is highest in people with a prior history of genital fungal infections. *

Urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

s (UTIs) may be more common with empagliflozin. Certain individual clinical trials have demonstrated an increase risk but cumulative data across multiple trials show no increase in UTI risk. * Empagliflozin reduces

systolic Systole ( ) is the part of the cardiac cycle during which some chambers of the heart contract after refilling with blood. The term originates, via New Latin, from Ancient Greek (''sustolē''), from (''sustéllein'' 'to contract'; from ''sun ...

and

diastolic Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventricu ...

blood pressure and can increase the risk of

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

, which can cause

fainting Syncope, commonly known as fainting, or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from ...

and/or falls. The risk is higher in older people, people taking

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

s, and people with reduced kidney function. * Slight increases in

Low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

(LDL)

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

can be seen with empagliflozin, in the range of 2–4% from baseline.

Serious

(DKA), a rare but potentially life-threatening condition, may occur more commonly with empagliflozin and other SGLT-2 inhibitors. While DKA is usually associated with elevated blood glucose levels, in people taking SGLT-2 inhibitors DKA may be seen with uncharacteristically normal blood glucose levels, a phenomenon called euglycemic ketoacidosis. The absence of elevated blood glucose levels in people on an SGLT-2 inhibitor may make it more difficult to diagnose DKA. The risk of empagliflozin-associated DKA may be higher in the setting of illness, dehydration, surgery, and/or alcohol consumption. It is also seen in type1 diabetes who take empagliflozin, which notably is an unapproved or "off-label" use of the medication. To lessen the risk of developing ketoacidosis (a serious condition in which the body produces high levels of blood acids called ketones) after surgery, the FDA has approved changes to the prescribing information for SGLT2 inhibitor diabetes medicines to recommend they be stopped temporarily before scheduled surgery. Empagliflozin should each be stopped at least three days before scheduled surgery. Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing. *

, a rare but serious infection of the groin, occurs more commonly in people taking empagliflozin and other SGLT-2 inhibitors. Symptoms include feverishness, a general sense of malaise, and pain or swelling around the genitals or in the skin behind them. The infection progresses quickly and urgent medical attention is recommended. * Empagliflozin can increase the risk of

low blood sugar Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

when it is used together with a sulfonylurea or insulin. When used by itself or in addition to metformin it does not appear to increase the risk of hypoglycemia.

Mechanism of action

Empagliflozin is an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), which is found almost exclusively in the

proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straig ...

s of

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ca ...

ic components in the kidneys. SGLT-2 accounts for about 90percent 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 C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical ...

and

Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...

. It is also available as the

combinations In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are t ...

empagliflozin/linagliptin Empagliflozin/linagliptin, sold under the brand name Glyxambi, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes. It is a combination of empagliflozin and linagliptin. It is taken by mouth Oral administrati ...

, empagliflozin/metformin, and empagliflozin/linagliptin/metformin.

Society and culture

Legal status

As of May 2013, Boehringer and Lilly had submitted applications for marketing approval to the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) and the US

(FDA). The drug was approved in the European Union in May 2014, and was approved in the United States 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.

Research

A single study shows that half a tablet of empagliflozin 25mg has similar glycemic efficacy as a full tablet.

References

External links

* {{Portal bar , Medicine Anti-diabetic drugs Boehringer Ingelheim Eli Lilly and Company brands Ethers Glucosides Wikipedia medicine articles ready to translate SGLT2 inhibitors