OBJECTIVES: Medication adherence and compliance are problems in young and elderly patients. With the increasing number of prescribed drugs, compliance drops and the number of adverse events increases. Furthermore, elderly patients are likely to have several co-morbidities, which could also affect their drug-consumption behavior considerably. In this study, our objective was to evaluate the compliance of anti-diabetic medication therapy in subjects with type 2 diabetes mellitus who initiated treatment with one of various oral anti-diabetic drugs or insulin. METHODS: Data for this study spanned the period January 1, 1995 to March 31, 2002 and were obtained from the Pharmetrics Patient-Centric Database, which is comprised of fully adjudicated medical and pharmaceutical claims for over 29 million unique patients from 52 health plans across the US. Patients with Type 2 diabetes mellitus (n=199,000) were classified into mutually exclusive treatment groups based on the therapy first received during the period of observation. Compliance rate was determined by the total number of days between first filled and last filled prescription plus days filled in the last prescription, divided by last fill date and the first fill date plus a 90-day gap. RESULTS: The pioglitazone group (n=2,730) ranked the highest in compliance with a mean of 85% (89% in the 55-64 age group) and a median of 91% compared to a mean compliance of 62% in the insulin group (n=27,274) (P <0.001) and 81% in the metformin group (n=52,469) (P=0.001). Similar results were found in newly diagnosed subjects. One-third of all pioglitazone patients added a second line therapy for diabetes compared to 43.9% on rosiglitazone (n=4,068). CONCLUSION: Compliance to treatment regimen for patients taking pioglitazone was higher than for patients on other anti-diabetic medications.