Dapagliflozin

Dapagliflozin is an active substance that is used to treat type 2 diabetes mellitus (antidiabetic), heart failure and chronic kidney disease. It belongs to the group of sodium-glucose cotransporter 2 inhibitors, SGLT2 inhibitors (sodium-glucose co-transporter 2). Dapagliflozin is also frequently used in combination preparations with saxagliptin or metformin. Both combination preparations are used to treat type 2 diabetes mellitus . Dapagliflozin, together with a special diet and physical activity, should help to reduce blood sugar fluctuations as much as possible.

Dapagliflozin has a blood sugar-lowering effect. It inhibits the sodium-glucose cotransporter 2 competitively, reversibly and selectively. Competitive means that the concentration of dapagliflozin must be higher than that of glucose in order to occupy the receptor. Glucose and dapagliflozin therefore compete for the receptor (competitive). Reversible means that the effect can be reversed and selective means that dapagliflozin can only occupy this one receptor.

SGLT2 is located in the nephron, the smallest functional unit of the kidney, where it ensures the reabsorption of sodium ions and glucose into the blood. By inhibiting it, more sodium ions and glucose are excreted in the urine, which leads to a lower blood glucose level. 90% of the reabsorption of glucose in the kidneys takes place via SGLT2. Importantly, unlike other antidiabetic drugs, dapagliflozin is insulin-independent, meaning that no insulin is needed to lower blood glucose levels. With dapagliflozin you also lose weight unintentionally.

The excretion of sodium via the urine also leads to more fluid (water) being excreted from the body. This in turn leads to a decrease in blood pressure.

The great advantage of dapagliflozin is that it is very difficult for people with type 2 diabetes to suffer hypoglycaemia when taking it, as the blood sugar level is not actively lowered by insulin, but only the absorption of sugar into the bloodstream is prevented. This means that life-threatening hypoglycemia (coma due to hypoglycemia) can only occur very rarely.

The bioavailability of dapagliflozin - i.e. the percentage of the active substance available in the blood - is 78%. The half-life, i.e. the time the body needs to excrete half of the active substance, is approx. 13 hours. The maximum plasma concentration (Cmax), i.e. the maximum concentration of the active ingredient in the blood plasma (liquid cell-free part of the blood), occurs after 1 hour of fasting. If you have eaten beforehand, the maximum plasma concentration is only reached after 2 hours.

Always take dapagliflozin exactly as described in the package leaflet or as advised by your doctor.

The usual recommended starting dose for type 2 diabetes mellitus is 5 mg per day and can be increased to 10 mg per day if necessary.

For all other clinical pictures(cardiac insufficiency, kidney disease) the usual dose is 10 mg per day.

The maximum dose is 10 mg per day.

The following side effects may occur:

• Angioedema may occur, symptoms may include:
  • Swelling of the face, tongue or throat
  • difficulty swallowing
  • hives
  • breathing difficulties
• Diabetic ketoacidosis may occur, symptoms of which may include
  • Nausea and vomiting
  • abdominal pain
  • excessive thirst
  • Rapid and deep breathing
  • confusion
  • drowsiness or tiredness
  • sweetish odor of the breath
• necrotizing fasciitis of the perineum may occur, which is a serious soft tissue infection of the genitals

If you experience any of the symptoms or illnesses described above, consult a doctor IMMEDIATELY or go to the nearest hospital!

Other side effects may include

• Urinary tract infections
• low blood sugar levels
• genital infection
• back pain
• increased urination
• Change in blood cholesterol levels
• Increase in the amount of red blood cells
• Decrease in creatinine clearance
• dizziness
• Skin rash
• Loss of too much body fluid
• thirst
• constipation
• Dry mouth
• Weight loss
• Increase in creatinine
• Increase in urea
• Inflammation of the kidneys

Interactions may occur if the following medicines are taken at the same time:

• Medications that ensure that more water is excreted (diuretics)
• Medication that also lowers the blood sugar level
• lithium

Dapagliflozin must not be taken in the following cases

• in case of allergy to dapagliflozin

For the treatment of type 2 diabetes mellitus, dapagliflozin can be used from the age of 10.

For the treatment of cardiac insufficiency or chronic renal ins ufficiency, dapagliflozin is approved from the age of 18.

Dapagliflozin should NOT be taken during pregnancy, as it can lead to malformations in the unborn baby in the 2nd and 3rd trimester. No increased risk to the unborn baby was found in animal studies in the 1st trimester of pregnancy, but as no studies in humans are available, dapagliflozin should also not be taken in the 1st trimester.

Dapagliflozin should NOT be taken during breastfeeding , as it passes into breast milk and there is a possibility of kidney developmental disorders in children under 2 years of age.

Dapagliflozin has been available in the European Union since 2012 and in the United States of America and Switzerland since 2014. It has been available as a combination preparation since 2017. In 2020, dapagliflozin was approved for the treatment of chronic heart failure (cardiac insufficiency ) and since 2021 for the treatment of chronic renal insufficiency (renal insufficiency). Since October 25, 2021, dapagliflozin is no longer approved for the treatment of type 1 diabetes mellitus.