The aim of the present study was to evaluate whether reduction of body weight is able to restore sensitivity to oral hypoglycaemic agents in obese non-insulin-dependent diabetic patients with secondary failure of to the anti-diabetic drugs. 80 obese patients (BMI approximately 30 kg/m2) with Type 2 diabetes lasting 1-30 years and showing hyperglycaemia for at least 3 months (51 on insulin, 29 on oral drugs) received an 800 kcal diet for 20-24 days, lost about 6.3% BMI, and returned to euglycaemia; 22 obese euglycaemic Type 2 diabetes patients (9 on insulin, 13 on oral therapy) underwent the same treatment, and lost approximately 8.3% BMI. As a result insulin could be withdrawn in 18 out of 60 patients and reduced (from 0.5 to 0.2 U.kg day) in the remaining patients. Oral therapy could be withdrawn in 17 out of 42 cases and reduced (from 12.1 to 8.6 mg glibenclamide/day) in the remaining cases. As a control group, 20 non obese (BMI < 24.0 kg/m2) hyperglycaemic Type 2 diabetic patients (10 on oral hypoglycaemic agents, 10 on insulin) with Type 2 diabetes lasting 1-26 years, underwent the same dietary regimen, lost about 3.2% of body weight, but could not withdraw insulin, which had to be started in 6 previously oral hypoglycaemic drugs treated patients. Systolic and diastolic blood pressure and serum cholesterol and triglyceride levels also decreased in obese, but not in non-obese Type 2 diabetes patients.(ABSTRACT TRUNCATED AT 250 WORDS)