Effect of subchronic metformin treatment on macronutrient selection in genetically obese Zucker rats

Metformin has been particularly recommended to be used in obese type 2 diabetic patients because of its weight decreasing and serum lipid profile normalizing effects. In the present study the effects of subchronic metformin treatment on macronutrient selection, weight gain and plasma insulin and glucose were investigated in 20 genetically obese male Zucker rats which were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Half of the rats were given metformin hydrochloride 320 mg/kg/day up to 18 days in drinking water. The other half of the animals received normal drinking water as a control. Metformin treatment significantly reduced 24 hr carbohydrate (P < 0.01), fat (P < 0.001) and protein (P < 0.01) intake. The proportion of fat of the total consumed energy was significantly increased by metformin (P < 0.01) while the proportion of protein was decreased (P < 0.05). In hunger stimulated feeding experiment metformin decreased selectively protein intake (P < 0.01). Changes in macronutrient selection were associated with reduced body weight gain in metformin treated rats (P < 0.001). Metformin markedly reduced the hyperinsulinaemia (P < 0.01) and plasma glucose levels (P < 0.05), which suggests improved glucose tolerance after metformin treatment. It is concluded that subchronic metformin treatment can modify the composition of energy intake in a macronutrient selective manner.