New research shows that concomitant use of dipeptidyl peptidase 4 (DPP-4) inhibitors and sulphonylureas increases the risk of hypoglycaemia in patients with type 2 diabetes mellitus (T2DM). The systematic review and meta-analysis included 10 studies, comprising 6,546 patients (4,020 received DPP-4 inhibitors plus sulphonylureas; 2,526 received placebo plus sulphonylureas) and included all currently available DPP-4 inhibitors. Risk of hypoglycaemia was increased by 50% when a DPP-4 inhibitor was added to sulphonylureas to treat patients with T2DM (RR 1.52, 95% CI 1.29–1.8), leading to one excess case of hypoglycaemia in every 17 patients treated during the first 6 months. The investigators note their findings “highlight the need to respect existing recommendations for dose reduction of sulphonylureas when initiating treatment with DPP-4 inhibitors.” Assessing whether these recommendations reduce the risk of hypoglycaemia is now urgently required.