3. INTRODUCTION
• Metformin (1,1-dimethylbiguanide), a biguanide derivate,
• First line oral therapy in the recent guidelines of the American
Diabetes Association
• Most widely prescribed drug to treat hyperglycemia, at least
120 million user worldwide[3]
• Insulin sensitizer[4]
• Monotherapy & in combination with all antidiabetic[1]
4. MECHANISM OF ACTION
• Decrease hepatic glucose production
through a mild inhibition of the
mitochondrial respiratory-chain
complex 1.[2]
• Decrease intestinal absorption of
glucose
• anti-oxidative properties of
metformin on endothelial cells[2]
6. • activation of AMPK is
the direct consequence of
a transient reduction in
cellular energy status
induced by the mild and
specific inhibition of the
respiratory-chain
complex 1
7. ACTIONS OF METFORMIN
Anti-obesity effects:
• Decreased appetite
• Increased GLP-1 secretion
Anti-hyperglycemic effects:
• Decreased intestinal carbohydrate absorption
• Inhibition of hepatic gluconeogenesis
• Enhancement of insulin-stimulated glucose transport in
skeletal muscle: increased activity of GLUT-4
8. Anti-lipidemic effects:
• Inhibition of lipolysis in adipose tissue
Anti-diabetic protective effects:
• Protection of β-cells from glucose toxicity and lipotoxicity
Hepatoprotective effects:
• Decreased hepatic insulin resistance and improved lipemia levels
Cardioprotective effects:
• Cumulative effects of decreased weight gain and better lipid profile
GLP-1 – glucagon-like peptide-1, AMPK – AMP-activated protein kinase, GLUT-4 – glucose transporter type 4,
9. PCOS is a common endocrinopathy, 5 to 15% women .
• Menstrual disturbance , Hyperandrogenism , polycystic ovary
on ultrasound.
•Insulin resistance, obesity
•Insulin sensitizer e.g. Metformin by alleviation of
insulin excess acting upon ovary and through direct
ovarian effects.
POLYCYSTIC OVARY SYNDROME[5]
10.
11. INDICATIONS
Obese patients with type II diabetes
Alone or in combination with sulfonylureas
CONTRAINDICATIONS
ݩHepatic impairment
ݩRenal impairment
ݩAlcoholism
ݩHeart failure
12. SIDE EFFECT
• 1.Metallic taste in the mouth
• 2. Gastrointestinal (anorexia, nausea, vomiting, diarrhea, abdominal discomfort)
• 3. Vitamin B 12 deficiency (prolonged use)
• 4. Lactic acidosis ( rare – 01/ 30,000-exclusive in renal & hepatic failure)
14. METFORMIN AS ANTI-CANCER
• T2DM increase risk of cancer
• Insulin resistance, Hyperglycemia and increase level of IGF-I due to
hyperinsulinemia promote carcinogenesis
• metformin reduce serum insulin and IGF-1 levels
• LKB1/AMPK pathway controlling cellular proliferation
• Apoptotic pathways by both caspase-dependent and caspase-independent
mechanisms
17. REFERENCES:
• 1. Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin: connections of metabolism
and cell proliferation. Annals of the New York Academy of Sciences 2011;1243:54-68 doi:
10.1111/j.1749-6632.2011.06285.x[published Online First: Epub Date]|.
• 2. Viollet B, Guigas B, Sanz Garcia N, et al. Cellular and molecular mechanisms of
metformin: an overview. Clinical science 2012;122(6):253-70 doi:
10.1042/CS20110386[published Online First: Epub Date]|.
• 3. Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diabetes & vascular
disease research : official journal of the International Society of Diabetes and Vascular
Disease 2008;5(3):157-67 doi: 10.3132/dvdr.2008.027[published Online First: Epub Date]|.
• 4. Hundal RS, Inzucchi SE. Metformin: new understandings, new uses. Drugs
2003;63(18):1879-94
• 5. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. nsulin-sensitising drugs (metformin,
rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome,
oligo amenorrhoea and subfertility. Cochrane Database Syst Rev.2010:
