Targeting elevated hepatic glucose production in type 2 diabetes (T2D) represents an attractive therapeutic approach. To investigate this, Axelsson et al. first analyzed liver gene expression in a diabetic mouse model, in combination with other genetic data, to identify a 50-gene liver disease signature. Interrogation of a library of 3800 drug signatures indicated that sulforaphane (SFN) — an isothiocyanate found in broccoli — may reverse this disease signature. In rats fed a high-fat or high-fructose diet, SFN prevented or reversed glucose intolerance. In obese patients with dysregulated T2D, concentrated broccoli extract improved fasting glucose and glycated haemoglobin without adverse effects.