NC

obese obese

Abbreviations: * indicates significant change; DM2, type 2 diabetes; FDR, first degree relatives of patients with type 2 diabetes; FG, fasting glucose; Fl, fasting insulin; MCR, metabolic clearance rate of glucose; NC, no change; PCO, women with polycystic ovary syndrome; ~ indicates values taken from a figure.

recently, in vivo treatment with metformin increased gene expression of the energy-dependent sodium-glucose cotransporter (SGLT1) in rat intestine (61). However, such a mechanism has not been confirmed in humans (27).

Weight Loss

Unlike other pharmacological therapies for type 2 diabetes (sulfonylureas, insulin) metformin treatment is not associated with weight gain. Consistently, clinical studies have shown either a small but significant decrease in body weight (28,62) or a significantly smaller increase in body weight compared to other forms of treatment (48). One study has shown that weight loss during metformin treatment was largely accounted for by loss of adipose tissue (24). This was explained by differential effects of metformin on adipose tissue and muscle. While metformin improves insulin sensitivity in muscle, it does not affect the antilipolytic action of insulin on adipose tissue (63). The overall effect of metformin on body weight is attributed to a reduction in caloric intake (48,64) rather than an increase in energy expenditure (24,32,65). Since

TABLE 3 Metabolic Studies in Humans without Type 2 Diabetes—Effects of Metformin
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