Antidiabetic Drugs

Posts Tagged ‘Obimet’

Metformin

Drug trade names: Glucophage XR, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex, Diaformin

Metformin is the only biguanide currently approved for the treatment of type 2 diabetes mellitus. It was originally developed in the 1950s in Europe and has been used there for many years. This agent was approved for use in the United States in 1995. While the mechanism of action is not completely clear at the present time, we do know that metformin is not an insulin secretagogue. It is effective in reducing hepatic and renal gluconeogenesis, thereby lowering fasting blood glucose values. Metformin also is effective in reducing postprandial blood glucose by a mechanism that is thought to involve retardation of gastrointestinal absorption. There also are some data that metformin improves peripheral insulin sensitivity by increasing the expression of glucose transporters and by increasing non-oxidative glucose metabolism.

Metformin usually is given initially as one 500-mg tablet once daily with a meal. One week later, the dose should be increased to 500 mg twice daily and can eventually reach a maximum of 2500 mg/day. Most studies show maximum effect with 2000 mg/day, with no additional efficacy at 2500 mg/day. There also are 850-mg tablets, allowing for convenient twice-daily dosing. Most studies analyzing the effects of metformin show that patients will on average lower HgbA₁C by 1.5%-1.9% when it is used as monotherapy.

This agent can be added to a sulfonylurea or insulin therapy (Current Oral Antidiabetic Therapy: A Summary of Oral Therapy), in which case a further decrease in HgbA₁C of 1.5% can be expected. Metformin alone is not associated with hypoglycemia, but this can occur when combined with insulin or sulfonylurea therapy. Metformin has the added benefit of reducing triglycerides and inducing mild weight loss in some overweight patients. The use of metformin to achieve glycemic control was studied in a subset of 342 obese diabetic patients in the United Kingdom Prospective Diabetes Study (UKPDS). Although reduction in myocardial infarction endpoints did not quite reach statistical significance (P<.052) in the insulin- and sulfonylurea-intensively treated groups, the obese diabetic patients treated with metformin had significant reductions in myocardial infarction, nonfatal stroke, and all cause mortality. The increased effect of metformin on prevention of macro vascular disease may be related to its known effects on decreasing low-density lipoprotein and triglyceride levels. More information should be available with the release of the UKPDS results concerning lipid profiles.

The main potential complication of metformin use is the risk of lactic acidosis. Unlike its predecessor phenformin, metformin does not strongly inhibit oxidative metabolism of glucose. Due to the absence of this effect, the risk of lactic acidosis is present, but much lower. The incidence of lactic acidosis is quite rare; however, it is recommended to avoid using metformin in patients who are predisposed to lactic acidosis or cannot metabolize lactate. Therefore, patients with a history of hepatic insufficiency, renal insufficiency, severe cardiac or respiratory disease, chronic metabolic acidosis, or alcohol abuse should not take metformin. It also is recommended that metformin should be stopped at the time of any interventional procedures, particularly surgical procedures or those requiring contrast dye. This will prevent a rise in metformin levels should acute renal failure occur. Metformin also should be used with caution in elderly patients secondary to their diminished renal function.

There are no known drug interactions and the most commonly seen side effect from metformin use is gastrointestinal irritation. Administering the tablet with food and beginning with the 500-mg dose usually prevents or ameliorates this side effect. Less than 5% of individuals will actually require cessation of metformin due to gastrointestinal side effects.