OBJECTIVES: Non-traditional outcomes (NTOs), those related with patient reported outcomes (PROs), economic and non-traditional clinical outcomes, are frequently being used to assess health interventions. We propose a standardized approach to assess the utility of NTO measures for use in health care decision making. METHODS: A systematic review of NTOs in Type 2 Diabetes Mellitus (T2DM) was conducted. Inclusion and exclusion criteria, data sources, search strategy, and data extraction and quality assessment of the studies and NTOs were defined. The degree of recommendation of each NTOs was based on the quality of the outcome and the scientific evidence to support it. Two independent reviewers carried out each activity. RESULTS: NTOs’ were assessed within a three-grade quality scale in terms of feasibility, validity, sensitivity, reliability, comparability and understanding. NTOs were categorized as key, important, and with not enough evidence to support its use in health decision-making. Case study in T2DM: 3805 citations and 235 potentially eligible full articles were retrieved and 153 studies met the inclusion criteria. Eighty-eight (5 clinical, 54 humanistic and 29 economic) NTOs in T2DM were retrieved. A total of 21.6% of the NTOs were considered key, 36.4% important and for 42% not enough evidence was found to support its use in T2DM. CONCLUSIONS: An evidence based understanding of NTOs’ validity to measure treatment outcomes in different conditions is needed since clinicians and payers may use them for decision-making purposes.