Objective: Oral antidiabetics have comparable safety and efficacy when used as fixed-dose combination therapies (FDCT) or loose-pill combination therapies (LPCT) for patients with T2DM. To evaluate alternative outcomes to safety and efficacy with FDCT, a systematic review of literature was conducted. Methods: Searches of Medline/Embase databases from 1998 to 2009 used predefined terms: 'fixed-dose combination', 'loose-dose combination' and 'diabetes'. Abstracts were reviewed from ISPOR, ADA, and EASD meetings (1998-2009). T2DM studies reporting adherence, patient-reported outcomes, costs, resource use or cost effectiveness were included. Results: Seventeen studies met the search criteria. Seven studies reported adherence. Adherence was 10-13% higher for FDCT than LPCT in patients starting combination therapy. Adherence decreased 1.5% and 10.0% when switching from monotherapy to combination therapy for FDCT and LPCT respectively (p<0.001). Switching to FDCT increased adherence 3.5%-12.4%, while remaining on LPCT changed adherence -1.5% to 5.0% (p<0.005). For patients newly initiating OAD medication, one study found no adherence advantage for FDCT compared with monotherapy or LPCT. Five RCTs reported treatment satisfaction. Four publications reported patients preferred FDCT using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). One publication reported improved satisfaction for one DTSQ subscale. Five abstracts reported economic outcomes. Two abstracts determined patients on FDCT used fewer healthcare resources and had decreased direct monthly healthcare costs versus LPCT. Two cost-effectiveness analyses determined clinical benefits from clinical trials translate into cost savings and increased life expectancy. One budget impact model reported minimal budget impact. Limitations: (1) There was limited published literature identified in this review. (2) FDCT are oral medications; these findings may only be relevant to those individuals taking an oral antidiabetic therapy. (3) Publication and reporting biases may exist. Conclusions: The published literature suggested that T2DM patients treated with FDCT may have better adherence, improved satisfaction, and lower direct medical costs, compared to those treated with LPCT.
