Products
Gliptins are commercially available in the form of film-coated tablets. Sitagliptin (Januvia) was the first representative to be approved in the United States in 2006. Today, various active ingredients and combination products are commercially available (see below). They are also called dipeptidyl peptidase-4 inhibitors.
Structure and properties
Some gliptins have a proline-like structure because the inhibited enzyme DPP-4 preferentially cleaves dipeptides that contain a proline (or alanine as in GLP-1) at the second position of the -terminus.
Effects
Gliptins (ATC A10BH) have antidiabetic and antihyperglycemic properties. Their effects are based on inhibition of the serine protease dipeptidyl peptidase-4 (DPP-4), which is found in many tissues, including the kidney, liver, lung, intestine, and immune cells. DPP-4 degrades the incretins GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) by cleaving the two -terminal amino acids (see Figure 1). These peptide hormones are released into the blood circulation after a meal in the intestine. They are produced by L- or K-cells. They have a short half-life in the range of a few minutes. Inhibition of the enzyme increases the concentration of incretins and their antidiabetic effects are enhanced. Incidentally, GLP-1 receptor agonists (GLP-1-RA) such as exenatide and liraglutide are peptide analogs of incretins with comparable properties. Gliptins:
- Glucose-dependently increase insulin release from pancreatic beta cells.
- Improve the sensitivity of beta cells to glucose and increase its uptake into tissues.
- Reduce glucagon secretion from alpha cells, leading to decreased glucose production in the liver.
- Slow gastric emptying and reduce the rate at which glucose enters the bloodstream.
- Enhance the feeling of satiety and do not cause weight gain.
Because gliptins are effective only when blood glucose is normal or elevated, they tend to cause fewer hypoglycemias.
Indications
For the treatment of type 2 diabetes. Gliptins are also combined with other antidiabetic agents such as metformin, sulfonylureas, SGLT2 inhibitors, glitazones, and with insulins.
Dosage
According to the SmPC. Tablets are usually taken once daily. Vildagliptin may also be administered twice daily.
Active Ingredients
- Alogliptin (Vipidia)
- Linagliptin (Trajenta)
- Saxagliptin (Onglyza)
- Sitagliptin (Januvia)
- Vildagliptin (Galvus)
Other representatives exist, which are not yet registered in many countries. In addition to the monopreparations, various fixed combinations are on the market, for example, Janumet or Galvumet, both additionally with metformin.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Some gliptins, such as saxagliptin, interact with CYP450 isozymes. Others, however, are neither CYP substrates nor inhibitors or inducers (e.g., vildagliptin).
Adverse effects
Potential adverse effects include gastrointestinal symptoms such as nausea, vomiting, and diarrhea, as well as headache and increased susceptibility to infectious diseases. This is because DPP-4 also plays a role in the immune system. Hypoglycemia occurs very rarely with monotherapy, but the risk is increased when combined with other antidiabetic drugs. Dangerous acute pancreatitis can occur rarely. It manifests as persistent, severe abdominal pain. Patients should be aware of these complaints.