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Introduction: There are different options to treat type 2 diabetes (DMT2) patients who began treatment with metformin and have not reached therapeutic golds. It is imperative to define rules to choose the best option, in these patients, as in those who have not achieved an optimal control under combined therapy. Aim: To define the best option between sulfonylureas, thiazolidinediones, DPP4 inhibitors, GLP-1 agonist or basal insulin, as second or third line treatment, in patients with DMT2 who have not reached therapeutic golds with metformin or combined therapy. Methods: A clinical practice guide has been developed following the broad outline of the methodological guide from the Colombian Ministry of Health and Social Welfare, with the aim of systematically gathering scientific evidence and formulating recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Conclusions: In patients with DMT2 who did not reach their therapeutic goal with metformin as a monotherapy (Hb1Ac <7%), addition of a second oral antidiabetic medication is recommended. it is recommended as a first step to add a DPP-4 inhibitor. It is suggested to add a SGLT2 inhibitor or a sulfonylurea having low risk of hypoglycemia as acceptable options. It is suggested to add basal insulin as a third antidiabetic medication if the combination of two pharmacological treatments does not enable the patient to reach and maintain the HbA1c goal. It is suggested to add a GLP-1 agonist if therapeutic failure appears in patients who remain obese (BMI ≥30 kg/m²), considering its potential to reduce weight
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