Drug therapy of obesity (DTO) has not been extensively used in diabetic patients so far, although excessive adipose mass largely contributes to insulin resistance which characterizes this disease together with insulin secretion failure. Orlistat is the sole currently available treatment, but several other new treatments are under investigation, such as sibutramine already marketed in other countries. Both drugs were found to be efficient in long term studies (1 year). However it is puzzling to note that weight loss induced by the drug as well as during placebo treatment is less pronounced in diabetic patients as compared with non diabetic subjects. Short term studies had already documented a lower response to DTO in diabetic patients by 2-fold. The reasons for this weight loss resistance in diabetics under DTO remain unclear and could be linked with metabolism. A weight loss > or = 5% initial body weight is required to obtain a significant lowering of HbA1c. Weight variations (weight delta > or = 5-10% initial weight) and results on glucose control (HbA1c delta > or = 0.5% after 3 to 6 months, or fasting blood glucose delta > or = 1 mmol/l within a few weeks) allow to define good DTO responders which should preferentially be eligible for this treatment. A decisional diagram is suggested.