Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus - A randomized, controlled trial

Background: Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement i n glycemic control but induces less weight gain. Objective: To determine whether bedtime insulin regimens differ with respec t to their effects on weight gain in patients with type 2 diabetes. Design: Randomized, controlled trial. Setting: Four outpatient clinics at central hospitals. Patients: 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 /- 1 kg/m(2)) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting p lasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]). Intervention: Random assignment to 1 year of treatment with bedtime interme diate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate -acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements. Measurements: Body weight, biochemical and symptomatic hypoglycemias, and i ndices of glycemic control. Results: At 1 year, body weight remained unchanged in patients receiving be dtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compar ed with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, th ose receiving bedtime insulin plus both oral drugs, and those receiving bed time and morning insulin, respectively. The greatest decrease in the glycos ylated hemoglobin value was observed in the bedtime insulin and metformin g roup (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percent age points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compar ed with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups. Conclusions: Combination therapy with bedtime insulin plus metformin preven ts weight gain. This regimen also seems superior to other bedtime insulin r egimens with respect to improvement in glycemic control and frequency of hy poglycemia.