OBJECTIVES: During its long course, Type 2 diabetes treatment involves complex interactions between patient-related non-biological and biological factors. A better understanding of these interactions is likely to strengthen efforts to reduce the health and economic burden of diabetes. We reviewed the literature regarding the relationships between patient-related factors, treatment outcomes, and standard economic parameters that are part of informed medical decision-making. METHODS: A systematic literature review was performed on articles dated 1993-2007 employing comprehensive medical subject heading (MeSH) and keyword searches in electronic reference libraries. Content matter and formatting criteria were pre-defined. Inclusion criteria were: 1) sole/predominant focus on T2D; 2) correlative analysis of at least 2 relevant parameters (self-management, treatment changes, patient-reported outcomes, clinical outcomes, and cost-related outcomes); and 3) use of questionnaires to capture patient-reported outcomes. Standardized data collection and abstracting techniques were followed according to Cochrane methodologies. RESULTS: A total of 110 manuscripts were retrieved, with 67 fulfilling all inclusion criteria. Most studies were retrospective (37/67; 55%) and from managed care settings (84%). Oral anti-diabetic drugs were a central focus, appearing in >90% of studies. Patient-related non-biological factors of care, particularly medication adherence and persistence, are well-researched (n=52) and shown to influence diabetes outcomes (eg, HbA1c and major hypoglycemia), cardiovascular risk, and mortality rates, as well as treatment-specific resource use (eg, hospitalization rates) and costs (by up to $3400 annually per patient). Patient satisfaction and wellbeing were also strongly associated with diabetes treatment outcomes. CONCLUSIONS: Robust correlations exist between self-management, treatment satisfaction/preferences, psychological wellbeing, and clinical outcomes in Type 2 diabetes. These interactions may significantly affect health and cost-related outcomes as well. Further research on the health economic impact of non-biological factors of care is warranted and would improve value-based resource allocation and appropriate access to care.