Exenatide

• UniProt: P26349

• CAS Number: 141758-74-9

Exenatide (trade name: BYETTA ®, manufactured by Lilly) is biotechnology exendin -4, a polypeptide in the saliva of the North American Gila Monster ( Heloderma suspectum ) was found. It was approved in 2005 as the first substance of the drug class of Inkretinmimetika as a drug.

Therapeutic aspects

Pharmacology

The structure of the peptide is similar to the human hormone glucagon-like peptide 1 (GLP -1). This small intestinal hormone that is released after a meal, stimulates the β - cells of the pancreas to increase the secretion of the glucose-lowering hormone insulin (see also incretin effect). Exenatide is exendin-4, such as from 39 amino acids, with an additional C-terminal amide group. It acts directly hypoglycemic by a glucose-dependent stimulation of insulin secretion and a reduction in the secretion of insulin antagonist glucagon., It is in the body less rapidly degraded than human GLP - 1 and is therefore more effective.

Approval Status

Since 2005, exenatide has been approved in the U.S. as a drug under the trade name Byetta. In 2006, an authorization by the European Commission and in 2007 came Byetta in Germany on the market. 2011 was a once only allowed to be injected weekly form of exenatide under the name Bydureon European.

Application and effect

Exenatide is not resorbed due to its chemical structure, for oral administration, but has to be injected subcutaneously. It is used in the treatment of type 2 diabetes as an alternative or as a complementary therapy, if by the sole use of oral antidiabetic agents with insufficient glycemic control can be achieved not tolerated, or oral medications. Exenatide is administered about 30 to 60 minutes before a meal subcutaneously. In addition to the blood glucose lowering it delays gastric emptying, reduces appetite and increases satiety. Since the effect on the blood sugar level is dependent, there is only a low risk for the occurrence of a hypo. The weight loss is independent of the gastrointestinal side effects such as nausea or vomiting.

Assessment

2008, the Federal Joint Committee (G -BA) has published a Notice therapy to treatment with exenatide. It informs the G -BA on the scope of approval as well as impact, effectiveness and risks, provides recommendations for the economic regulation way to the costs and any necessary precautions when prescribing.

Adverse effects (side effects)

The most common side effects occur in approximately half of the patients at least once during the treatment gastrointestinal disturbances such as nausea, vomiting and diarrhea. Their expression is in most patients, mild to moderate and depends on the dosage. The frequency and severity of these side effects decrease in the course of therapy. More common side effects are headache, dizziness, temporary weakness and restlessness.

Partly reports on the occurrence of acute pancreatitis with exenatide could not be safely attributed to the drug in trials, so found a 2010 published retrospective study, no increased risk of acute pancreatitis with exenatide, but a generally increased in diabetics risk for the occurrence of acute pancreatitis

2011 informed the Drug Commission of the German Medical Association ( AKdÄ ) on two cases in which patients treated with exenatide patients of pancreatic cancer was diagnosed. The AkdÄ recommended the use of exenatide only in special situations. Studies on the relationship between GLP1 agonist, similar to DPP4 inhibitors and cancer risk are inconsistent.

The development of antibodies to exenatide is documented, but it is not known whether these lead to long-term development of tolerance. Acute immunological reactions such as anaphylactic immune response were observed very rarely.

Trade names

Bydureon, Byetta