OBJECTIVES: The SGLT2 inhibitor dapagliflozin (DAPA) increases glucosuria in an insulin-independent manner resulting in reductions in hyperglycemia, weight and BP with a low risk of hypoglycemia. Glipizide (GLIP) reduces hyperglycemia by increasing beta cell insulin secretion with risk of hypoglycaemia and weight gain. We conducted a cost analysis of treating patients over 4 years to two relevant composite endpoints: (1) HbA1c lowering of ≤0.5%, no major or minor hypoglycaemic events and weight loss ≥3% and (2) HbA1c lowering of ≤0.5%, no major or minor hypoglycaemic events and weight loss ≥5%.  METHODS: The Cardiff Diabetes model was used to estimate the cost of treating T2DM patients to two composite endpoints in a UK setting, using 208 week data from a previously published double-blind randomised clinical trial of dapagliflozin (DAPA) vs glipizide (GLIP) (NCT00660907). Calculation of costs included drug acquisition costs, cost for adverse events, micro- and macrovascular complications, and BMI related costs The cost of treating one patient to the composite endpoints using DAPA+MET versus GLIP+MET over 208 weeks was calculated as total cost per treatment arm divided by number of patients that reached the composite endpoint in each arm. RESULTS: The number needed to treat was 4 for DAPA+MET and 35 for GLIP+MET and overall cost of treating one patient over 208 weeks to composite endpoint (1) was £12,042 for DAPA+MET and £50,040 for GLIP+MET. The corresponding figures for composite endpoint (2) was 4 for DAPA+MET and 47 for GLIP+MET with corresponding costs of £12,666 and £59,366. CONCLUSIONS: The cost of treating one patient to the composite endpoints was approximately 4.1-4.7 times higher with GLIP+MET compared to DAPA+MET. These results demonstrate that when multiple treatment goals, including weight loss and reduction of hypoglycaemic events are targeted, the cost of treating patients with DAPA+MET is lower compared to GLIP+MET.