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 pr ofile normalizing effects. In the present study the effects of subchro nic metformin treatment on macronutrient selection, weight gain and pl asma insulin and glucose were investigated in 20 genetically obese mal e Zucker rats which were maintained on a free-feeding self-selection p aradigm with three pure macronutrient diets of carbohydrate, fat and p rotein. 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 rec eived normal drinking water as a control. Metformin treatment signific antly reduced 24 hr carbohydrate (P < 0.01), fat (P < 0.001) and prote in (P < 0.01) intake. The proportion of fat of the total consumed ener gy was significantly increased by metformin (P < 0.01) while the propo rtion of protein was decreased (P < 0.05). In hunger stimulated feedin g 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 tr eatment. It is concluded that subchronic metformin treatment can modif y the composition of energy intake in a macronutrient selective manner .