Objective: To evaluate the safety and efficacy of treatment with insulin alone, insulin plus metformin, or insulin plus troglitazone in individuals with type 2 diabetes.
Research design and methods: A total of 88 type 2 diabetic subjects using insulin monotherapy (baseline HbA(lc) 8.7%) were randomly assigned to insulin alone (n = 31), insulin plus metformin (n = 27), or insulin plus troglitazone (n = 30) for 4 months. The insulin dose was increased only in the insulin group. Metformin was titrated to a maximum dose of 2,000 mg and troglitazone to 600 mg.
Results: HbA(lc) levels decreased in all groups, the lowest level occurring in the insulin plus troglitazone group (insulin alone to 7.0%, insulin plus metformin to 7.1%, and insulin plus troglitazone to 6.4%, P < 0.0001). The dose of insulin increased by 55 units/day in the insulin alone group (P < 0.0001) and decreased by 1.4 units/day in the insulin plus metformin group and 12.8 units/day in the insulin plus troglitazone group (insulin plus metformin versus insulin plus troglitazone, P = 0.004). Body weight increased by 0.5 kg in the insulin plus metformin group, whereas the other two groups gained 4.4 kg (P < 0.0001 vs. baseline). Triglyceride and VLDL triglyceride levels significantly improved only in the insulin plus troglitazone group. Subjects taking metformin experienced significantly more gastrointestinal side effects and less hypoglycemia.
Conclusions: Aggressive insulin therapy significantly improved glycemic control in type 2 diabetic subjects to levels comparable with those achieved by adding metformin to insulin therapy. Troglitazone was the most effective in lowering HbA(lc), total daily insulin dose, and triglyceride levels. However, treatment with insulin plus metformin was advantageous in avoiding weight gain and hypoglycemia.