Sitagliptin, a modern antidiabetic agent which is weight neutral and associated with low rate of hypoglycaemias, is being increasingly used in type 2 diabetes mellitus (DM). However, there is a paucity of data about its efficacy and safety in beta-thalassaemia major (β-TM). This retrospective case series of five patients (mean age of 45 years) is the first study evaluating the use of sitagliptin in patients with β-TM and DM. Four patients responded well to sitagliptin, as evidenced by a decrease in fructosamine by 77 and 96μmol/L (equivalent reduction in HbA1c of 1.5% and 1.9%) observed in two patients and reduction in the frequency of hypoglycaemia without worsening glycaemic control in two others. One patient did not respond to sitagliptin. No patients reported significant side effects. This study provides evidence that sitagliptin may be considered, with caution, for use in patients with β-TM and DM, under the close monitoring of a Diabetologist.