Its mechanism of action involves the suppression of endogenous glucose production, primarily by the liver. Whether the drug actually has an insulin sensitising effect in peripheral tissues, such as muscle and fat, remains somewhat controversial. Nonetheless, because insulin levels decline with metformin use, it has been termed an 'insulin sensitiser'.

Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular outcomes in patients with diabetes. Cardiovascular disease, impaired glucose tolerance and the polycystic ovary syndrome are now recognised as complications of the insulin resistance syndrome, and there is growing interest in the management of this extraordinarily common metabolic disorder.

While diet and exercise remain the cornerstone of therapy for insulin resistance, pharmacological intervention is becoming an increasingly viable option.

We review the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits it provides over and above its effect on glucose levels alone.

We also discuss its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease.

29. Cardiovascular side effects of thiazolidinediones.

Sang Thrombose Vaisseaux. Number 16, volume 3, 151-9, mars 2004, Mini？\revue Résumé Article gratuit Author(s) : Franck Boccara, Ariel Cohen

Summary : A new class of antidiabetic agents, thiazolidinediones, has been introduced for the treatment of type 2 diabetes mellitus. The prescription of rosiglitazone and pioglitazone in Europe is restricted to a combination with metformin or sulfonylureas. These new drugs may have cardiovacular side effects such as increased plasma volume, edema (3？\6%) and dose？\related weight gain (1？\4 kg after 6 month therapy). The benefit on glucose metabolism (decreased insulinemia, Hb A 1c) for the prevention of cardiovascular risk has not yet been evaluated. There is no data available concerning possible cardioprotective effects of TZDs in large human cohorts. Some benefits have been demonstrated in animals such as improvement of endothelial dysfonction, inotropic effects on left ventricular contraction, decrease and angiotensin activation leading to a beneficial effect on ventricular remodeling, antiinflammatory (attenuation expression of cytokines and chemokines) and anti？\atherogenic effects in diabetes mellitus. Large observational studies of tolerance and clinical benefit focusing on cardiovacular protection in diabetes mellitus treated by TZDs are warranted.