OBJECTIVES: To determine the cost-effectiveness of exenatide versus insulin glargine as adjuncts to metformin for the treatment of patients with type 2 diabetes mellitus (T2DM) who have failed monotherapy. METHODS:  A cost-effectiveness analysis was made by a discrete events model at the patient’s level that simulates the incidence of the complications of the disease, and it considers a time horizon of 20 years. The model perspective is from the Colombian health system. The main outcomes are the quality-adjusted life years (QALY) and the economic results of the disease and its complications. Direct costs were updated to the year 2016 and a discount rate of 5 % was applied, both for costs and for health outcomes. The risk to develop complications were taken from the risk formulas of UKPDS68 and UKPDS66. RESULTS: Exenatide generates fewer events of congestive heart failure and deaths due to macrovascular events as well as a 4.5 kg weight loss and a decreased of 4 mmHg in systolic blood pressure versus insulin glargine. Exenatide contributes 1.24 more discounted QALY per patient compared to insulin glargine and has an ICER of US $ 3,953 per patient, which is lesser than one per capita GDP in Colombia (US $ 6,049). In the willingness to pay curves, exenatide has a 61 % probability of being the choice strategy with a willingness to pay of one GDP per capita in Colombia. CONCLUSIONS: From the perspective of the Colombian health system, exenatide is a highly cost-effective strategy versus insulin glargine in patients with T2DM who cannot be adequately controlled with metformin monotherapy, with a great impact over their weight loss and QALY.