Objective: To systematically review the literature and published recommendations from four Health Technology Assessment Agencies (HTAAs) in order to report what may have contributed to the dearth of reimbursement of non-injectable insulins. Methods: Two independent researchers systematically reviewed the published literature from 2003-2007 using the MEDLINE, EMBASE, and Cochrane databases. Publications of human trials involving non-injectable insulins reported in any language were included. Keywords such as Insulin, Oral OR Inhalation OR Aerosols OR Mist OR Spray OR Sublingual OR Nebulizers OR Vaporizers OR Intranasal OR Dermal OR Buccal with the indication of Diabetes Mellitus Type 1 OR Diabetes Mellitus Type 2 were used. Clinical trials, with at least one intervention being a non-injectable insulin, were included. Exclusion criteria included inappropriate research design, outcomes not reported and/or not extractable. Listing decisions posted on the websites of the National Institute for Health and Clinical Excellence in the UK, the Scottish Medicines Consortium, the Institute for Quality and Efficiency in Health Care in Germany, and the Common Drug Review in Canada were reviewed. Results: Of 233 identified citations, 20 articles were included for full text review. Reported outcomes included standard clinical efficacy measures (e.g., postprandial glucose levels, HbA1c reduction) and tolerability. Few articles (N=3) reported outcomes such as patient preference for treatment, general health-related quality of life, final health outcomes, and/or satisfaction. No studies were specifically designed for reimbursement purposes. There was a paucity of utility measures, the lack of which was the main criticism by the HTAAs leading to either “not to list” or very restricted listing recommendations. Other HTAA comments were the use of secondary versus primary clinical outcomes and the absence of adherence information. Conclusion: Clinical studies for non-injectable insulins do not include adequate information and/or outcomes that are required by decision makers for reimbursement recommendations.