(Metformin) Type 2 diabetes medication.

Metformin

A trusted companion in diabetes management.

Metformin is an oral medication commonly

prescribed to manage type 2 diabetes. It

belongs to the class of drugs known as

 biguanides.

 

What to learn?

·    Clinical uses

·    Mechanism of action

·    Drug interaction

·    Contraindication

·    Toxicity

·    Key points

Clinical uses

1.      Endothelial dysfunction

2.      Diabetic thrombophilia

3.      Microalbuminuria

4.      Oxidative stress

5.      Inflammation

6.      Blood pressure

7.      Dyslipidaemia

8.      Obesity

9.      Hyperglycaemia 

Mechanism of action

·    Inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon- induced elevation of cyclic adenosine monophosphate (CAMP) with reduced activation of protein kinase A (PKA), inhibition of phosphate dehydrogenase, and an effect on gut microbiota.

·    Ultimately, it decreases gluconeogenesis (liver glucose production).

·    It also has an insulin-sensitizing effect with multiple actions on tissues including the liver, skeletal muscle, endothelium, adipose tissue, and the ovary.

·    The average patient with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one-third.

·    In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake (by inducing the phosphorylation of GLUT4 enhancer factor), decreases insulin-induced suppression of fatty acid oxidation, and decreases absorption of glucose from the gastrointestinal tract.

·    Increased peripheral use of glucose may be due to improved insulin binding to insulin receptors. The increase in insulin binding after metformin treatment has also been demonstrated in patients with NIDDM.

·    AMPK probably also plays a role in increased peripheral insulin sensitivity, as metformin administration increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. Some metabolic actions of metformin do appear to occur by AMPK- independent mechanisms.

Drug interaction

·    Metformin is usually a first-line drug to treat Type 2 diabetes mellitus.

Metformin is also found to be useful to treat various conditions include...

1.     Prediabetes

2.     Gestational diabetes mellitus (GDM)

3.     Polycystic Ovarian Syndrome (PCOS)

4.     Obesity

5.     Cancer, etc.

·    Interaction between one or more coadministered medications leading to reduced therapeutic efficacy or enhanced toxicity, is termed as "Adverse drug interaction".

·    Metformin may interact with the following drugs...

1.         iodinated Contrast Materials (ICMs)

2.         H₂ receptor blockers (Cimetidine, Ranitidine)

3.         Proton pump inhibitors

4.         Antimicrobials (Trimethoprim, Cephalexin, Rifampin, Dolutegravir)

5.         Ranolazine

6.         Anticancer Drugs (Vandetanib, Imatinib, Nilotinib, Gefitinib, and     Erlotinib)

7.         Beta adrenergic blockers (Atenolol, Metoprolol)

·    Maiden NM, Jumale A, Balasubramaniam R. Drug Interactions of Metformin Involving Drug Transporter Proteins. Advanced pharmaceutical bulletin. 2017 Dec;7(4):501.

Contraindications

1. Patients with Type I diabetes

2. Patients with hepatic or renal impairment

3. Alcoholic liver disease

4. Chronic obstructive airway disease

5. Congestive heart failure, MI

6. Pregnancy and lactation

7. Peripheral vascular disease

8. Any condition associated with hypoxia

9. In patients > 70 yrs of age.

10. Care while using diuretics concomitantly

Clinical uses

·    Clinical evidence from randomised trials and observational studies supports improved long- term macrovascular outcomes in people with type 2 diabetes treated with metformin.

·    Multiple biological mechanisms contribute to these benefits, which are still being studied intensively today.

Toxicity

·    Lactic acidosis esp in patients with renal impairment,

·    Gl effects: anorexia, vomiting and diarrhoea, abdominal pain.

·    Rarely hypoglycaemia.

·    Fulminant Gi distress leading to ARF, which↑ lactic acidosis.

Key points

·    Metformin use is currently contraindicated in people with type 2 diabetes mellitus who have renal impairment, congestive heart failure or severe liver disease or who are 80 years of age or older.

• From our knowledge of the mechanism of action of metformin, increased production of lactic acid will occur at high toxic drug levels.

• Alternative antihyperglycemic agents (oral agents or insulin) can be used effectively in patients with contraindications to metformin use.

• It is not yet known how much people with contraindications to metformin use will benefit from the unique vascular protection offered by the drug.

• Given the uncertainty of the primary data, the currently accepted contraindications should be maintained.