Pharmacology of metformin and liraglutide:

Mechanism of action:

METFORMIN: Metformin is an AMPK (adenosine mono phosphate kinase) enzyme agonist. It activates the AMPK which phosphorylates the GLUT-4 enhancer factor which opens the channel gates of plasma membrane resulting in insulin independent glucose uptake. The three main actions of metformin are. 1. It increases the glucose uptake by muscle cells. 2. It inhibits the glucose absorption from gut wall. 3. And suppresses hepatic gluconeogenesis. This unique mechanism of three way action without the risk of hypoglycaemia it regulates the homeostasis.

LIRAGLUTIDE: Liraglutide belongs to a class of drug increatin mimetics as it mimics the effect of increatin GLP-1(glucagon like peptide). And it is also called glucagon like peptide analogue. Liraglutide triggers the release of GLP-1 hormone which is released from the Lcells of the intestine. The actions of liraglutide are mainly. 1. It increases the activity of GLP-1 hormone which stimulates the secretion of insulin from the BETA cells. 2. Supresses the action of glucagon (hormone that increases the production of glucose by the liver). 3. It delays the gastric emptying time hence supresses the appetite.

COTRAINDICATIONS:
METFORMIN: Metformin is contraindicated in patients 1. With renal and hepatic disease. 2. Hypoxic pulmonary disease. 3. Heart failure or shock. 4. Patients during pregnancy. 5. Patients with diabetes 1. 6. Use of metformin should be temporarily discontinued before or on radiographic study (CT. Scan, angiogram etc.) Can be continued after confirming the kidney function test. 7. And contraindicated in conditions that predispose to lactic acidosis.

LIRAGLUTIDE:

Liraglutide is contraindicated in patients 1. Already at the risk of medullary thyroid cancer. 2. Patients with diabetes 1. 3. One shouldnt breast feed while using liraglutide. 4. Contraindicated in patients with kidney or liver disease. 5. Contraindicated in patients with history alcoholism. 6. And patients with high blood pressure and high triglyceride level. 7. Its also contraindicated in pregnant women.

ADVERSE DRUG REACTIONS :

METFORMIN:
1.

Long term use of metformin may interfere with vitamin B12 absorption.

2. It may cause impaired renal function in few cases. 3. Use of metformin may cause lactic acidosis (very rare 1in 10,000 patients). 4. It may cause anorexia. 5. GIT upsets like nausea, vomiting, diarrhoea, increases flatulence (building up gas in stomach or intestine).

LIRAGLUTIDE: The adverse drug reactions of liraglutide are 1. Since it is a protein, body may develop antibodies to liraglutide.

2. Pancreatitis (inflammation of pancreas) is more often seen. 3. Side effects like nausea, vomiting, diarrhoea, abdominal pain, heart burn are seen during the initial stages of treatment. 4. Combining liraglutide with drugs that increase the release or doses of insulin may cause hypoglycaemia. 5. Liraglutide slows down the transit of food and drugs through the intestine therefore decrease the absorption of drugs taken orally.

CLINICAL USES:

METFORMIN: 1. Metformin is mostly used in type 2 diabetes. 2. It is also used in the treatment of polycystic ovary syndrome. 3. Used in treatment of non alcoholic fatty liver disease. 4. In treatment of premature puberty. 5. And also in type 2 diabetes patients with obesity.

LIRAGLUTIDE: Liraglutide is mainly used in the treatment of diabetes 2 and in few cases for weight management and it is also used as appetite suppressant.

REFFERENCES:
http://www.japi.org/june_special_issue_2010/Article_07.pdf http://www.nejm.org/doi/full/10.1056/NEJMp1001578 http://www.diabetesuffolk.com/Drugs/Liraglutide.htm

http://www.actabiomedica.it/data/2009/2_2009/rossi.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC209533/ http://www.druglib.com/druginfo/metformin/description_pharmacology/

http://www.medicinenet.com/script/main/art.asp?articlekey=112714 H.P.Rang, MM.Dale,JM.Ritter,PK.Moor (2003). Pharmacology. 5th ed. London: Churchill Livingstone. P385-391. Brody, Larner, Minneman (1998). Human pharmacology molecular to clinical. 3rd ed. USA: Mosby. p541-557.