The effect of metformin treatment was studied in nine patients with mild (fasting plasma glucose concentration less than 7.5 mmol.l-1) non-insulin-dependent diabetes mellitus (NIDDM) and fasting plasma triglyceride (TG) concentration greater than 2.0 mmol.l-1. Individuals were studied before and three months after receiving 2.5 g/day of metformin. Mean hourly plasma glucose concentration from 8 AM to 4 PM (7.5 +/- 0.5 vs 6.5 +/- 0.4 mmol.l-1, p less than 0.001), as well as glycosylated hemoglobin levels (7.0 +/- 0.5 vs 6.2 +/- 0.2%, p less than 0.02) were significantly lower following metformin treatment. The improvement in glycaemic control was not associated with an improvement in insulin stimulated glucose disposal as measured by the glucose clamp technique. Mean hourly day-long concentrations of plasma insulin (519 +/- 81 vs 364 +/- 64 pmol.l-1, p less than 0.001), FFA (502 +/- 45 vs 460 +/- 35 mu mol.l-1, p less than 0.01), and triglyceride (3.60 +/- 0.33 vs 3.02 +/- 0.31 mmol.l-1, p less than 0.001) concentrations were significantly lower following three months of metformin treatment. Finally, fasting plasma TG concentration, very low density lipoprotein (VLDL)-TG, and VLDL-cholesterol concentrations were significantly decreased, while high density lipoprotein (HDL)-cholesterol concentration was significantly increased following metformin therapy. Thus, metformin administration to individuals with NIDDM, who did not have significant fasting hyperglycaemia, led to a decrease in plasma glucose, insulin, FFA, and TG concentration, and an increase in plasma HDL-cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)