The authors hypothesized that a metformin (MET)-diet would improve symptoms of idiopathic intracranial hypertension (IIH) in women who also had polycystic ovary syndrome (PCOS) or hyperinsulinemia without PCOS. Changes in weight, papilledema, headache, visual fields, and overall life status were prospectively assessed in response to 6 to 14 months on 2.25 g/day MET-diet or diet alone in 36 women with IIH, 23 with PCOS, selected by baseline body mass index (BMI) > or = 25, and no previous surgery for IIH. Overall life status was graded using a self-reported 1-5 scale (1 = well, normal activities; 2 = unwell, usual activities; 3 = poor, usual activities; 4 = poor, no usual activities; 5 = totally disabled). Conventional treatment for IIH was maintained unchanged during MET-diet intervention. The diet was hypocaloric (1500 calories/day), high protein (26% of calories), and low carbohydrate (44%). Of the 23 women with PCOS, 20 received MET-diet and 3 diet only (could not tolerate MET). Of the 13 women without PCOS, 7 were hyperinsulinemic and received MET-diet and 6 received diet alone. The 3 treatment groups (diet only [n = 9], PCOS-MET-diet [n = 20], and hyperinsulinemia-MET-diet [n = 7]) did not differ by median entry BMI (33.3, 37.6, and 35.7 kg/m(2)) or by duration of treatment (10.2, 11.4, and 10.9 months). Median percent weight loss was greatest in the PCOS-MET group (7.7%, P = 0.0015), was 3.3% in the diet only group, and 2.4% (P = 0.04) in the hyperinsulinemia-MET group. Papilledema significantly improved in the diet-alone group from 100% at baseline to 13% (P = 0.03), and in the PCOS-MET group from 95% to 30% (P = 0.002). If headache persisted on therapy, it was less intense-less frequent (P = 0.03) in the diet-only group and in the PCOS-MET group (P = 0.04). As many women with IIH have PCOS, and because weight loss is central to IIH treatment, diet-MET is a novel approach to treat IIH in women with concurrent PCOS or hyperinsulinemia without PCOS.