AIMS To evaluate the efficacy of a lifestyle intervention programme including meal replacements and increased physical activity upon body weight, diabetes control and other cardiovascular risk factors in obese, poorly controlled, insulin-treated, type-2-diabetic individuals and to assess the impact of concomitant rosiglitazone (RSG) therapy. METHODS This 6-month intervention study included 21 patients with type 2 diabetes mellitus (DM) requiring insulin therapy with haemoglobin A1c (HbA1c) > 7% and with a body mass index (b.m.i.) > 27. All subjects were enrolled in a 6-month lifestyle intervention programme and randomized to placebo or RSG 4 mg/day. Participation in the lifestyle programme included meal replacements, increased intake of fruits and vegetables and increased daily physical activity. Measured end-points included body weight, waist circumference, blood pressure, HbA1c and serum lipids, before entry into the study. RESULTS The baseline mean b.m.i. was 36.4 and the mean HbA1c was 9.0%. The greatest weight losses occurred during the first 12 weeks (19 lbs for RSG, 13.4 lbs for placebo) with a greater weight loss at each point for the group receiving RSG. Waist circumference declined by 2.8 and 4.0 inches for the placebo and RSG groups. Systolic BP declined 16.2 mmHg in the placebo group and 14.3 mmHg in the RSG group. Diastolic blood pressure decreased by 12.8 mmHg in the placebo group. HbA1c was reduced significantly by 1.3% for the placebo group and 1.1% in the RSG group. DISCUSSION This study demonstrates the benefits of lifestyle intervention using meal replacements and increased physical activity with resultant modest weight loss in long-standing, poorly controlled type 2 diabetes. RSG did not impede weight loss and, in fact, amplified some of the positive benefits of lifestyle intervention.