Bromocriptine, a potent dopamine D(2) receptor agonist, has been shown to reduce insulin resistance, glucose intolerance and hyperlipidaemia in both numerous animal studies and in Phase II studies. Bromocriptine has been used worldwide for over 20 years to treat Parkinson's disease, macroprolactinoma and other disorders; it has been found to be generally safe. We therefore investigated the possible beneficial effects of Ergoset(R) (Ergo Science Corp.), a new quick release formulation of bromocriptine, on glycaemic control and serum lipid profile in obese Type 2 diabetic subjects in two large Phase III studies. A large, randomised, double-blind placebo-controlled study was conducted in which Ergoset was given once daily at 8 am. (4.8 mg maximum dose) for 24 weeks as adjunctive therapy to sulphonylurea (485 subjects) to obese Type 2 diabetics held on a weight- maintaining diet. Treatment efficacy parameters included change from baseline in glycated haemoglobin A(1c) (HbA(1c)), fasting and post-prandial serum glucose, insulin, triglyceride and free fatty acid levels. Baseline glycated haemoglobin, fasting glucose, insulin, triglyceride and free fatty acid levels did not differ between treatment groups. and on average were 9.4 +/- 0.05%, 222 +/- 2 mg/dl, 24 +/- 1 µU/ml, 248 +/- 11 mg/dl, and 850 +/- 32 µEq/l, respectively. A similarly designed study of Ergoset as monotherapy in Type 2 diabetics (154 subjects) with similar baseline clinical characteristics was conducted. Addition of Ergoset treatment to sulphonylurea reduced percent glycated HbA(1c) by 0.55 (P < 0.0001) (approximately 1.0 for responders, 65% of population), fasting and post-prandial glucose by 23 and 26 mg/dl (P < 0.0002), fasting and post-prandial triglycerides by 72 and 63 mg/dl (P < 0.005) and fasting and post-prandial free fatty acids by 150 and 165 µEq/l (P < 0.05), relative to placebo. Twelve percent of all Ergoset subjects, compared to 3% of placebo subjects, withdrew from the study due to adverse events. The most common events causing withdrawal were nausea, dizziness, asthenia, and rhinitis (representing 4.5, 3.3, 2.0, and 0.8% of the total Ergoset populations, respectively). The incidence of serious adverse events did not differ between Ergoset- (3.4%) and placebo- (4.3%) treated subjects. Ergoset as monotherapy also improved glycaemic control (0.56 HbA(1c) decrease relative to placebo after 24 weeks of treatment; P < 0.02). Once daily Ergoset treatment improves glycaemic control and serum lipid profile and is well-tolerated in obese Type 2 diabetics.