Products
In 2012, dapagliflozin (Forxiga) was approved in the EU as the first agent in the new group of SGLT2 inhibitors. Several drugs are now on the market worldwide (see below).
Structure and properties
The SGLT2 inhibitors are derived from phlorizin, a -glucoside and natural substance first isolated from apple tree bark in 1835. Phlorizin itself is not suitable for diabetes treatment because it is not selective for the cotransporter SGLT2 and it has insufficient oral bioavailability. It is already enzymatically hydrolyzed by glucosidases in the digestive tract.
Effects
SGLT2 inhibitors (ATC A10BX) have antidiabetic and antihyperglycemic properties. Their effects are based on increased excretion of glucose in the urine. They are selective inhibitors of sodium–glucose cotransporter 2 (SGLT2). This transporter is responsible for the reabsorption of glucose at the proximal tubule of the nephron. SGLT2 inhibitors are selective and do not inhibit the transporter SGLT1, which is responsible for the absorption of glucose in the intestine and is present in other organs. What is special about this group of drugs is that, unlike other antidiabetic drugs, their mechanism of action is independent of insulin. SGLT2 inhibitors can also reduce body weight because they flush calories out of the body, so to speak.
Indications
For the treatment of type 2 diabetes. Some are also used for the treatment of type 1 diabetes. This in combination with insulins.
Dosage
According to the drug label. The drugs are usually taken once daily in the morning.
Active ingredients
The following active ingredients have marketing authorization:
- Canagliflozin (Invokana).
- Dapagliflozin (Forxiga)
- Empagliflozin (Jardiance)
- Ertugliflozin (Steglatro)
- Ipragliflozin (Suglat, first approved in 2014 in Japan).
- Tofogliflozin (Apleway, Deberza, initial approval 2014 in Japan).
Clinical candidates or precursors without approval:
- Remogliflozin (GSK)
- Sergliflozin
- T-1095 (precursor)
- Phlorizin (precursor)
Contraindications
SGLT2 inhibitors are contraindicated in the presence of hypersensitivity. Full details of precautions and drug-drug interactions are substance-dependent and can be found in the drug label.
Adverse effects
The majority of possible adverse effects are a result of increased glucose concentration in the urine. The most common adverse effects include vaginal thrush in women, acalculitis in men, urinary tract infections, frequent urination, and increased urine output. Hypoglycemia is rare but may occur in combination with other antidiabetic agents. Due to water loss, dehydration is possible with subsequent symptoms such as dizziness and low blood pressure.