Metformin Side Effects

Metformin hydrochloride has been studied in patients with pre diabetic conditions both as a preventive measure, such as in patients with impaired glucose tolerance and the insulin resistance syndrome but without overt DM, and as a treatment for polycystic ovary syndrome (PCOS).

Findings from the biguanides and prevention of risks in obesity study suggested that metformin may prevent the progression of impaired glucose tolerance to over type 2 DM. In this study, obese, non diabetic subjects with android body fat distribution received metformin hydrochloride (850 mg twice daily) or placebo for 3 years. metformin hydrochloride treated patients had a lower body weight and lower concentrations of fasting serum insulin, low density lipoprotein cholesterol and the tissue plasminogen activator than did placebo treatment patients. Among patients who had impaired glucose tolerance at entry, metformin significantly lowered FPG concentrations.

The diabetes prevention program a large multi center US trial studied the effects of metformin hydrochloride treatment or intensive life style modification on the progression of DM in high risk adults with impaired glucose tolerance. Eligible participants were randomly assigned to standard lifestyle recommendations plus metformin hydrochloride to placebo, or to an intensive lifestyle modification alone. The study was stopped early, but study participants were monitored on average for nearly 3 years. The primary end point was clinical diabetes, defined as FPG of at least 126 mg/dl. The cumulative incidence of the primary end point was significantly lower in the metformin group and in the intensive lifestyle modification group than in the placebo group. No differences were apparent by sex or ethnic group.

The clinical features of insulin resistance syndrome also known as syndrome X or the metabolic syndrome are hyper insulinemia with or without impaired glucose tolerance or increased fasting glucose, central adiposity, dyslipidemia, obesity, endothelial dysfunction and hypertension. People with insulin resistance syndrome have an increased risk of cardiovascular disease and the condition often progress to over type 2 DM. Because metformin improves insulin sensitivity, it has been used in clinical trials to prevent or delay the development of DM and to reduce the risk for cardiovascular disease. In studies of patients with impaired glucose tolerance, metformin administration improved insulin sensitivity as measured by both the euglycemic hyperinsulinemic clamp technique and peptide concentrations. metformin hydrochloride administration also improved dyslipidemia , fibrinolytic activity and insulin sensitivity in patients with abdominal obesity.

Polycystic ovary syndrome is the most common cause of chronic anovulation and infertility. Women with PCOS have significant underlying insulin resistance with compensatory hyperinsulinemia as a primary cause of this disorder, independent of obesity. These women typically exhibit features of the insulin resistance syndrome, including central obesity, hypertriglyceridemia, hypertension, decrease in high density lipoprotein cholesterol and an increase in plasminogen activator inhibitor concentration.

When administrated to lean or obese insulin resistant women with PCOS, metformin reduces p-450c17 alpha activity and serum free testosterone and LH concentrations. Metformin also normalizes 17 alpha hydroxyprogesterone concentrations, restores menstrual cycling and normalizes the altered serum ratio of LH to follicle stimulating hormone. Additionally metformin improves glucose tolerance and insulin sensitivity, reduces insulin concentration and promotes weight loss.

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