Metformin Uses | Mechanism of Action | ADRs | Dose | Diabetes Mellitus

  Metformin

Common Brands: (Glucophage, Glucophage XR, Fortamet, Glumetza)

Biguanides

It is also known as an insulin sensitizer because it increases glucose uptake and utilization by target tissues.  That is why it's called an insulin sensitizer as it decreases insulin resistance but it does not secrete insulin. Only one biguanide is available as metformin to control glycemic management of type 1 diabetes mellitus or type 2 Diabetes Mellitus. The main target of metformin is fasting glucose levels. Metformin is recommended to be initialed at diagnosis of type 2 diabetes mellitus.

Mechanism of action of metformin

1.   Metformin work by inhibiting hepatic gluconeogenesis leading to the reduction of hepatic glucose output.

2.   It Also slows down intestinal absorption of glucose as a minor role in diabetes mellitus.

3.   It Also enhances glucose uptake by fat and muscles leading to increase insulin sensitivity.

4.   Metformin also has the ability to reduce hyperlipidemia.

 

Important Note:

In Type 2 diabetes mellitus, the liver produces excess glucose that becomes the major reason for high glucose levels in patients. Patients lose weight because of loss of appetite.

Blood Glucose Levels:

Diabetes in nonpregnant adults and children

•       Fasting blood glucose  ≥ 126mg/dL
•      Random blood glucose and symptoms of hyperglycemia  ≥ 200 mg/dL
•       A1c  ≥ 6.5%
•       Oral glucose tolerance test (OGTT) using an oral glucose load equivalent to 75g anhydrous glycerin dissolved in water: > 200 mg/Dl

 

Metformin Doses:

• 500 mg once or twice daily with meals.

Metformin has a 6-hour duration of action. It should be discontinued when the Scr for females is > 1.4 and for males >1.5mg.

 

Adverse effect 

Up to 30% of patients using metformin are affected by gastrointestinal effects. These effects can be reduced or minimized by taking the drug with food, by starting the drug in low doses.

      1.   Transient Nausea
2.   Abdominal cramping ( typically lasts up to 2 weeks)
3.   Lactic acidosis ( rare but fatal)
4.   Weight loss ( it’s a minimal effect that occurs initially but not a continued effect)
5.   Metallic taste
6.   Sweating
7.   Metformin also reduces vitamin B12 levels. So monitoring of Vit. B12 levels required.
8.   Hypoglycemia when used in combination with other drugs.

 

Contraindications:

1. Contraindicated in renal/hepatic disease due to the potential for lactic acidosis. (does not cause renal impairment itself)

•       Acute myocardial infarction
•      Alcoholism

Enlist the factors responsible for variation in drug responses?

Factors responsible for variation in drug responses:

1. Alteration in the concentration of drug that reaches the receptors

2. Variation in concentration of endogenous ligands 

3. Alteration in number or function of receptors 

4. Changes in components of response distal to the receptor