Glucagon-like peptide-1 (GLP-1) mimetics (or receptor agonists) stimulate glucose dependent insulin secretion from beta-cells only when the glucose level is above the normal range; they cease to act between meals when glucose levels are lowered, thereby eliminating the risk of hypoglycemia. However, GLP-1 agonists cannot be orally administered and require a subcutaneous injection.

Drugs in this class include exenatide synthetic and liraglutide.

• EXENATIDE SYNTHETIC

  Tradename(s)	Byetta®
  Company(ies)	Eli Lilly / Amylin Pharmaceuticals
  Available doses	5 mcg per subcutaneous dose in a 1.2 ml prefilled pen (60 doses) and 10 mcg per subcutaneous dose in a 2.4 ml prefilled pen (60 doses)
  Dose per day	twice daily
  Side-effects	nausea
  Elimination half-life	2.4 hours
  Metabolism	predominantly eliminated by glomerular filtration with subsequent proteolytic degradation
  US patent status	Expires in 2017
  US FDA status	approved April 2005
  EMEA status	approved November 2007
  Indication
  Byetta® is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione, but have not achieved adequate glycemic control.
  Comments
  Byetta® is derived from the saliva of the giant lizard the Gila. Lilly and Amylin co-promote Byetta in the US and Puerto Rico. Lilly has exclusive rights in other territories. Eli Lilly reported sales of $219M in 2006, $650M in 2007 and $751M in 2008. In October 2007, the FDA issued an alert for healthcare professionals after reviewing postmarketing reports of acute pancreatitis in patients treated with Byetta. In August 2008, the FDA announced that since issuing its firsts alert in October 2007, they has received reports of 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta. Amylin Pharmaceuticals and Eli Lilly submitted Byetta as a monotherapy treatment for type 2 diabetes to the FDA in Q1 2008. The FDA is expecting to review the application in 2009.

• LIRAGLUTIDE

  Tradename(s)	Victoza®
  Company(ies)	Novo Nordisk AS
  Available doses	One pre-filled pen contains 18 mg liraglutide in 3 ml pen and is used to administer a .6 mg, 1.2 mg or 1.8 mg dose.
  Dose per day	once daily (by subcutaneous injection)
  Side-effects	gastrointestinal disorders
  Elimination half-life	13 hours
  Metabolism	metabolised in a similar manner to large proteins without a specific organ having been identified as major route of elimination
  US patent status
  US FDA status	not yet approved
  EMEA status	approved July 2009
  Indication
  The marketing authorisation covers: combination treatment with metformin or a sulphonylurea in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin or sulphonylurea, and combination treatment with metformin and a sulphonylurea or metformin and a thiazolidinedione in patients with insufficient glycaemic control despite dual therapy.
  Comments
  On 23 May 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the US for the approval of Victoza® for the treatment of people with type 2 diabetes. Victoza is a solution for injection that contains the active substance liraglutide. It is available in pre-filled pens (6 mg/ml).