OBJECTIVES: Diabetes-related cost-effectiveness analyses (CEA) have become more common, though little is known about the actual use of cost-saving services in real-world settings. This study systematically reviewed cost-effectiveness analyses of diabetes interventions, identified cost-saving diabetes services, and estimated potential gains from increasing use of cost-saving diabetes interventions in the United States.  METHODS: We conducted a systematic review of cost-utility analyses (CUAs) related to diabetes published through 2012, using the Tufts Medical Center CEA Registry. We also examined factors independently associated with favorable ratios. We used the 2008-2012 Humedica electronic medical record data to estimate the potential cost savings and health benefits gained by switching patients to cost-saving diabetes interventions identified in our review.  RESULTS: We identified 196 diabetes CUAs. Most examined pharmaceuticals (55%) and focused on treatment rather than prevention (70%). Most used a health care payer perspective (71%) and were industry-sponsored (52%).  Of 497 published cost-utility ratios, 82% examined a guideline-recommended intervention. Approximately 73% of interventions examined in diabetes CUAs were found to be either cost-saving or below $50,000 per QALY. Logistic regression analysis showed that higher-quality CUAs or CUAs conducted from the US perspective were more likely to report favorable ratios. Ratios for surgical interventions and interventions recommended by diabetes guidelines were more favorable than other intervention types. Of 7,907 eligible patients in Humedica, 6,500 could be shifted to cost-saving treatments, saving more than $11 million and gaining more than 1,800 QALYs. CONCLUSIONS: Our findings suggest that most diabetes interventions evaluated by CUAs are recommended by practice guidelines and may provide good value for money. Our results also indicate that patients and the health care system could benefit considerably from shifting to greater use of cost-saving interventions.