Kristine L.

Gregorio

Pharmacology

METFORMIN – is used with a proper diet and exercise program and possibly with other medications to
control high blood sugar.

- to treat high blood sugar levels caused by type 2 diabetes mellitus

Pharmacokinetics

- Metformin undergoes renal excretion and has a mean plasma elimination half-life after oral
administration of between 4.0 and 8.7 hours. This elimination is prolonged in patients with renal
impairment and correlates with creatinine clearance.
- Metformin is well absorbed orally, is not bound to serum proteins
- It is not metabolized
- Excretion is via the urine
- Onset of action: Within days; maximum effects up to 2 weeks
- Distribution: Vd: 654 ± 358 L; partitions into erythrocytes; concentrates in liver, kidney, and GI
tract
- Protein binding: Negligible
- Metabolism: Not metabolized by the liver
- Bioavailability: Absolute: Fasting: 50% to 60%
- Half-life elimination: Plasma: 4 to 9 hours; Blood ~17.6 hours
- Time to peak, serum: Immediate release: 2 to 3 hours; Extended release: 7 hours (range: 4 to 8
hours)
- Excretion: Urine (90% as unchanged drug; active secretion)

Pharmacodynamics

- Insulin is an important hormone that regulates blood glucose levels. Type II diabetes is
characterized by a decrease in sensitivity to insulin, resulting in eventual elevations in blood
glucose when the pancreas can no longer compensate. In patients diagnosed with type 2
diabetes, insulin no longer exerts adequate effects on tissues and cells (called insulin resistance)
and insulin deficiency may also be present.
- Metformin reduces liver (hepatic) production of glucose, decreases the intestinal absorption of
glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and
utilization. In contrast with drugs of the sulfonylurea class, which lead to hyperinsulinemia, the
secretion of insulin is unchanged with metformin use.
- Metformin lowers both basal and PPG. It works mainly by suppressing excessive hepatic glucose
production, through a reduction in gluconeogenesis [30]. Other potential effects of metformin
include an increase in glucose uptake, an increase in insulin signaling, a decrease in fatty acid
and triglyceride synthesis, and an increase in fatty acid β-oxidation. Metformin may also
increase glucose utilization in peripheral tissues, and possibly reduce food intake and intestinal
glucose absorption. As metformin does not stimulate endogenous insulin secretion, it does not
cause hypoglycemia or hyperinsulinemia, which are common side effects associated with other
antidiabetic drugs.