Farxiga (dapagliflozin) is a medication used to treat adults with type 2 diabetes mellitus, heart failure and chronic kidney disease. It comes in the form of a tablet.
What has the FDA approved Farxiga to treat?
The US Food and Drug Administration (FDA) has approved Farxiga for use in adults:
- along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes.
- to reduce the risk of cardiovascular death, hospitalization for heart failure in adult patients with heart failure, when the heart is weak and cannot pump enough blood to the rest of your body.
- to reduce the risk of further worsening of your kidney disease, end-stage kidney disease (ESKD), death due to cardiovascular disease, and hospitalization for heart failure in adults with chronic kidney disease.
- to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes who also have known cardiovascular disease or multiple cardiovascular risk factors.
How does Farxiga work?
Farxiga works by increasing the amount of glucose (blood sugar) removed when we urinate. It also works by reducing the increased activity of the sympathetic nervous system that contributes to the progression of heart failure and the increased intraglomerular pressure that contributes to CKD.
Farxiga works in a part of the kidneys called the proximal renal tubule. It is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. SGLT2 allows glucose to be reabsorbed back into the body with the aid of a sodium molecule which powers the process. By inhibiting SGLT2, Farxiga decreases the reabsorption of glucose and sodium, which:
- Increases the amount of glucose excreted or removed from the body when we urinate. This helps to reduce glucose levels in patients with type 2 diabetes.
- Increases the amount of sodium in another area of the kidney called the distal tubule, which helps in heart failure by:
- Reducing the pressure under which the heart fills.
- Reducing the resistance the heart has to pump against.
- Reducing the elevated activity of the sympathetic nervous system that is associated with heart failure. The sympathetic nervous system’s elevated activity increases the force with which the heart contracts, which leads to it pumping out more blood. It also works to maintain arterial perfusion - the blood flow within the arterial system - by narrowing the smaller peripheral blood vessels. Initially this compensates for the failing heart, but ultimately it contributes to the problem.
- Reduces intraglomerular pressure, which is thought to be one of the ways that Farxiga works in people with CKD, although how it works in this patient population is not fully understood.
Intraglomerular pressure is the pressure within a glomerulus - a network of small blood vessels found in the beginning of the nephron in the kidneys. The glomerulus filters the blood, enabling small molecules, waste and fluid to pass into the tubule. The tubule then returns the substances you need back to your blood and removes the waste and excess fluid as urine.
About type 2 diabetes
Type 2 diabetes is a chronic disease characterized by high levels of sugar (glucose) in the blood. After we eat our body breaks down the carbohydrates we have consumed into simple sugars, which are a source of energy or fuel for our body. The amount of sugar in our blood is regulated by a hormone called insulin, which helps to ensure that our blood sugar is not too high (hyperglycemia) or too low (hypoglycemia). When our blood sugar levels go up, insulin tells our bodies to store the excess sugar or glucose in our cells for later use.
People with type 2 diabetes can become resistant to the effects of insulin, meaning that although their blood sugar levels are too high, their bodies don’t respond to minimize the excess blood sugars. The pancreas, the organ responsible for making insulin, initially attempts to combat rising blood sugar levels by producing more and more insulin. Eventually it becomes unable to keep up and can stop working altogether.
About heart failure
Heart failure is a chronic and progressive condition in which the heart cannot keep up with its workload and can no longer pump oxygen-rich blood around your body as well as it should. When the cells in our body don’t get the oxygen-rich blood they need it can result in fatigue and shortness of breath.
Our hearts are made up of four chambers. The top two are called atria and the bottom two are ventricles. The right atrium and ventricle are involved in collecting the blood that has already travelled around the body and pumping it to the lungs to be replenished with oxygen. Oxygen-rich blood is then sent back through the left atrium to the left ventricle, which pumps it out around the body.
When heart failure begins to develop our bodies employ a number of different mechanisms to help compensate, including enlargement of the heart, pumping blood faster, narrowing of blood vessels and more. Eventually though, the body can no longer compensate and symptoms start to develop.
To measure how effectively a heart pumps blood doctors measure your ejection fraction. This measures how much blood is left in your left ventricle after it contracts to pump oxygen-rich blood out around your body. Your ejection fraction is provided as a percentage and a normal measurement is between 50-70%. An ejection fraction of 41-49% may be considered borderline and a measurement under 40% may indicate heart failure.
About chronic kidney disease
Chronic kidney disease (chronic renal disease) results in a slow loss of kidney function over time. As the kidney’s fail waste can build up in the blood causing illness. Failing kidneys can cause high blood pressure, anemia, osteoporosis, nerve damage and more. Kidney disease can also lead to heart problems and damaged blood vessels. Kidney disease can progress and lead to kidney failure. Diabetes and high blood pressure (hypertension) are two of the main causes of chronic kidney disease.