Dapagliflozine

SGLT2 inhibitor for the treatment of type 2 diabetes mellitus, heart failure and chronic kidney disease(CKD) according to guidelines.

see SGLT2 inhibitors

Mechanism of action: SGLT2i are based on a new mode of action that differs fundamentally from insulin and other oral antidiabetics. SGLT2i are based on the selective reversible inhibition of the sodium-dependent glucose transporter SGLT-2 (sodium-glucose co-transporter 2) in the proximal tubule of the kidney. This leads to increased excretion of glucose (glucosuria) and, as the co-transport of sodium is also inhibited, to increased excretion of sodium in the urine (natriuresis). The inhibition is selective for the SGLT-2 transporter. The SGLT-1 transporter is not inhibited. However, the inhibition of SGLT2 is not complete and is also partially compensated by the SGLT-1 transporter further distally in the renal tubule. Therefore, hypoglycemia or electrolyte shifts do not occur.

For further details see SGLT2 inhibitors.

Oral availability, rapid absorption, high plasma protein binding, maximum plasma levels within 1-2 hours, elimination within 24-48 hours after discontinuation.

Metabolized predominantly via glucuronide conjugation via various UDP-glucuronosyltransferase enzymes. Hardly via CYP. Therefore hardly any significant pharmacokinetic interaction with other drugs.

In case of renal dysfunction eGFR ≤45 ml/min glucose-lowering effect reduced, additional glucose-lowering medication may be necessary. The cardio- and nephroprotective effect is maintained even with impaired renal function.

Do not use in case of severe liver dysfunction or, if necessary, initially use the lowest dose and increase gradually (see specialist information).

Heart failure (HF) according to guidelines

applicable from the age of 18.

Type 2 DM according to guidelines

applicable from 10 years of age.

Renal insufficiency (CKD) according to guidelines

applicable from 18 years of age.

for further information see SGLT2 inhibitors

contraindicated during pregnancy and breastfeeding

for further information see technical information.

Recommended dosage 1x daily, independent of food and possible at any time of day.

For further information see specialist information.

The most common side effect is an increased risk of genital and urinary tract infections due to glucosuria. The risk can be reduced by good hygiene and care measures. Infections are rare and can generally be treated well with the usual treatment measures.

A serious adverse effect or complication is Fournier's gangrene, a necrotizing fasciitis of the perineum, which occurs very rarely. The risk is increased in patients with immunodeficiency of any cause, poor general health and nutritional status, alcoholism, drug addiction, smoking, advanced age, obesity and others. The disease is life-threatening and requires immediate surgical treatment and debridement.

Complication: Atypical ketoacidosis, very rare but potentially life-threatening! When treated with SGLT2i, ketoacidosis can occur even with only slightly elevated or normal blood glucose levels! Very important and requires special attention in terms of clinic and diagnosis!

Ketoacidosis is very likely if the following symptoms occur: nausea, vomiting, anorexia, abdominal pain, severe thirst, difficulty breathing, confusion, unusual tiredness, drowsiness, loss of consciousness.

Risk is increased in situations with increased endogenous insulin requirement or relative insulin deficiency, such as major surgical interventions (fasting, stress), especially major surgical interventions and bariatric surgery, but also diagnostic procedures that require fasting, low-calorie diets or fasting and dietary changes, especially with reduced carbohydrate intake, low-carb diets, malabsorption, severe fluid loss and excessive physical exertion, excessive alcohol consumption, or acute serious illnesses such as infections, gastroenteritis, myocardial infarction, stroke, etc.etc.
Even with combination treatment of SGLT2i with insulin, reducing the insulin dose can lead to an increased risk of ketoacidosis. Therefore, strict monitoring of blood glucose levels and possibly ketone bodies and increased awareness of symptoms is necessary!

Diagnosis: monitoring of ketone body concentration in blood (ketone body determination in urine not sufficient), pH≤7.3; serum bicarbonate ≤15mmol/l; anion gap ≥12mmol/l.

Immediate discontinuation of SGLT2i and treatment in case of ketoacidosis!

Pause treatment in case of infections and acute illnesses as well as in case of dietary changes, etc. Discontinuation possible 3 days before surgery. (AVP, Arneiverordnung in der Praxis Volume 50(1), March 2023) (patients should be informed about possible ketoacidosis, risk situations and symptoms!)

At the start of treatment, there may be a temporary, reversible increase in serum creatinine and a reduction in eGFR = part of the mode of action and the nephroprotective effect through osmotic diuresis and TGF. In patients with severely impaired renal function, close monitoring and treatment by an experienced nephrologist is recommended (clinical data and studies, as well as guidelines and benefit assessment for the treatment of CKD with low eGFR refer to dapagliflozin and empagliflozin; see product information for the respective product).

For further information see SmPC.

SGLT2i should not be used in type 1 diabetes mellitus, as the risk of life-threatening ketoacidosis is too high.

SGLT2i are not to be used in patients under 18 years of age (no data available). Exception: dapagliflozin for type 2 DM approved from 10 years of age (Forxiga® Information for healthcare professionals).

SGLT2i should not be used in case of hypersensitivity to one of the active substances or other components of the medicine. Contains lactose compound, therefore not to be used in patients with rare hereditary galactose intolerance, complete lactase deficiency or glucose-galactose malabsorption (see relevant information for healthcare professionals).

For further information, see specialist information.

Dapagliflozin ^Forxiga® 5mg 10mg