We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA 1c in newly diagnosed patients with type 2 diabetes. Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels, lipids, and adverse events. Patients were randomised to receive acarbose, titrated step-wise to a maximum of 100 mg three times daily ( n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in three doses ( n=48). The two treatments were considered equivalent if the two-sided 90% confidence interval (CI) for the difference in mean HbA 1c levels was within the range −0.4 to 0.4%. Results were analysed on an intention-to-treat, per-protocol and on worst-case basis. Both agents reduced the HbA 1c percentage and fasting blood glucose levels. The difference in mean decrease of HbA 1c was 0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case analysis, assuming no change in HbA 1c for dropouts, yielded a difference in mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide (95% CI 0.3, 1.7). There were no significant differences in post-load blood glucose, fasting and post-load insulin levels, or lipids. In the acarbose group significantly more patients (15 versus 3) discontinued therapy because of adverse effects, mostly of gastrointestinal origin. We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes.