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Second generation - Metformin
Correct elevated hepatic glucose output
Inhibits gluconeogenesis from substrates like lactate, pyruvate, glycerol and aminoacids
Opposes gluconeogenic actions of glucagon
Enhances the glucose transport activity of insulin in muscles and glycogen and lipid synthesis
Decrease intestinal absorption of glucose
Does not increase insulin secretion
Not hypoglycaemic, even at high doses
Decreases FBG by 25 to 30%
Decreases A1c by 1 to 2 %
Improves the response of muscle to insulin
Weight neutral or weight reduction
Lipid profile improves
Metformin common side effects
Symptoms abate with time
Or reduction of dose
Discontinuation in 3% to 5% patients
IR side effects
Immediate release (IR) formulation transits rapidly through the digestive system.
IR tablet rapidly dissolves and the drug moves too quickly through the gastrointestinal system before complete absorption takes place.
This often causes a disturbance in the colon resulting in side effects such as diarrhoea, flatulence.
Side effects of Metformin
Incidence much less with XR
The most widely publicised adverse effect of biguanide therapy
In clinical settings of increased lactate production or reduced lactate clearance, such as liver disease, renal dysfunction or other illness causing tissue hypoxia, especially cardiac or respiratory dysfunction, use of biguanides may provoke lactic acidosis
Incidence of lactic acidosis was clearly much greater with Phenformin than with Metformin, being about 10-15 times higher
Metformin causes little or no rise in plasma lactate levels.
Significant Renal disease (Sr. Creat >1.4 F, 1.5 mg/dL for M)
Known hypersensitivity to Metformin
Congestive heart failure
Acute or chronic metabolic acidosis
In patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.
Cimetidine reduces renal clearance
Alpha glucosidase inhibitor: reduction in bioavailability
Drugs causing hyperglycaemia
As an adjunct to diet and exercise to improve glycaemic control in patients with T2DM
Individualised on basis of effectiveness and tolerance not exceeding max. recommended dose
Given once daily with evening meal
Start at low dose with gradual dose escalation
Start with: 500 mg OD and increase with 500 mg on weekly basis up to maximum of 2000 mg
Must be swallowed whole and never crushed or chewed
Metformin and alcohol
Alcohol intake: Alcohol is known to potentiate the effect of Metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving Cetapin???? XR.
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