Metformin
Mechanism :
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Indication :
- Diabetes mellitus-Type 2
- Insulin resistance - as adjunct to insulin
Contraindications :
Known hypersensitivity to metformin hydrochloride, renal disease or renal dysfunction, cardiovascular collapse (shock), acute myocardial infarction, septicemia, congestive heart failure requiring pharmacologic treatment, acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma are contraindications for its use.
Dosing :
10-16 years: Initial: 500 mg orally, every 12 hours. Increase every week by 500 mg.
Max dose: 2000 mg/day.
>17 years: Initial: 500 mg orally, every 12 hours or 850 mg per day with meals.
Maintenance: 1500-2550 mg/day in 2-3 divided doses with meals. Max dose: 2550 mg/day.
Adverse Effect :
Common adverse effects include anorexia, nausea, vomiting, flatulence, asthenia, indigestion. Others: lactic acidosis (rare), hypoglycaemia, low serum vitamin B12 levels, chills, dizziness.
Interaction :
Cimetidine: Reduces the renal clearance of metformin.
Anticoagulant therapy: May require adjustment.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 40-50 | 25–50% of dose |
| 10-40 | 25% of dose. |
| <10 | Avoid. |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Avoid |
| HD | Dialysed. Avoid |
| HDF/High flux | Dialysed. Avoid |
| CAV/VVHD | Probably dialysed. Avoid |
Hepatic Dose :
Children = 10 years and adolescents: Avoid metformin; liver disease is a risk factor for the development of lactic acidosis during metformin therapy.