Those who because of cost or side effects were transferred back to twice daily mixed insulin alone had no significant change in glycemic control. Another surprising outcome of this study was the weight loss seen in patients successfully converted from insulin to combination oral therapy. Initial weight loss was undoubtedly due to discontinuation of insulin and, with it, the need to eat more. However, the weight loss continued, and I believe it was due to the utilization of metformin. With better glycemic control, weight gain is to be expected because of restoration of fluid volume and muscle mass and reversal of glycosuria and urinary calorie loss.
Weight gain occurs with sulfonylureas, insulin, and thiazolidinediones.
However, in spite of better glycemic control, monotherapy with metformin results in weight loss or no weight gain. A prospective, randomized, double-blinded study has shown that metformin decreases appetite and calorie intake. The question of whether insulin therapy in type 2 diabetes patients could be discontinued and replaced with oral monotherapy is often asked. The natural history of type 2 diabetes, in which glycemic control is obtained initially with monotherapy before combination therapy, makes this unlikely. Therefore, discontinuation of insulin therapy in type 2 diabetes requires the effects of at least two hypoglycemics with different mechanisms of action.