The effect of
metformin treatment was studied in 13 patients with
noninsulin-dependent diabetes mellitus (
NIDDM), whose fasting plasma
glucose concentration was greater than 10 mmol/L with maximal sulfonylurea doses. Patients were studied before and 3 months after receiving 2.5 g/day
metformin. The fasting plasma
glucose concentration (12.4 +/- 0.8 vs. 8.8 +/- 0.7 mmol/L), mean hourly postprandial plasma
glucose concentration from 0800-1600 h (14.0 +/- 1 vs. 9.4 +/- 0.9 mmol/L), and
glycosylated hemoglobin level (12.3 +/- 0.6% vs. 9.0 +/- 0.6%) were all significantly (P less than 0.005-0.001) lower after the administration of
metformin. The improvement in
glycemic control was associated with a 24% increase (P less than 0.05) in
insulin-stimulated
glucose uptake during
glucose clamp studies and a 16% decrease in basal hepatic
glucose production (P less than 0.05). Mean hourly concentrations of plasma
insulin (411 +/- 73 vs. 364 +/- 73 pmol/L) and FFA concentrations (440 +/- 31 vs. 390 +/- 40 mumol/L) were also lower after 3 months of
metformin treatment. However, neither
insulin binding nor
insulin internalization by isolated monocytes changed in response to
metformin. Finally, plasma
triglyceride,
very low density lipoprotein triglyceride, and
very low density lipoprotein cholesterol were significantly decreased (P less than 0.01-0.001), and
high density lipoprotein cholesterol was significantly increased (P less than 0.001) after
metformin treatment. Thus, the addition of
metformin to sulfonylurea-treated patients with
NIDDM not in good
glycemic control significantly lowered fasting and postprandial plasma
glucose concentrations, presumably due to the combination of enhanced
glucose uptake and decreased hepatic
glucose production. Since the
dyslipidemia present in these patients also improved, the results suggest that
metformin may be of significant clinical utility in patients with
NIDDM not well controlled with
sulfonylurea compounds.