OBJECTIVES: Hypertension and dyslipidemia elevate risk of cardiovascular diseases in diabetic patients. The risk, however, can be reduced considerably by drug therapy. Therefore, adherence with prescribed drug therapy is especially important. The study described adherence patterns of major drug classes of oral antidiabetic (AD), antihypertensive (AH), and lipid-lowering (LL) therapy in veterans with type 2 diabetes. METHODS: The study used VA pharmacy prescription data from 1998 to 2004. Patients were included if they initiated at least one of AD/AH/LL in 2000. Concomitant therapy was defined as initiating at least two of AD/AH/LL within 90 days. Compliance was measured in six-month intervals following initiation of therapy. Patients were considered compliant if filled prescriptions were sufficient for covering >= 80% of days. Persistence was measured as the number of days of continuous therapy, with 60 days between 2 prescriptions as the grace period. RESULTS: A total of 65,806, 31,910, and 48,445 patients were examined for adherence to AD, AH, and LL, respectively. Angiotensin receptor blockers (ARBs) had the longest mean persistence (AH, 787.7 days), followed by â-blockers (AH, 764.7 days), sulfonylureas (AD, 734.7 days), ACE inhibitors (AH, 726.3 days), calcium channel blockers (AH, 708.1 days), metformin (AD, 700.0 days), á-blockers (AH, 698.5 days), thiazolidinediones (AD, 674.0 days), statins (LL, 663.6 days), diuretics (AH, 660.3 days), and fibrates (LL, 557.8 days). Percentage of patients adherent with therapy dropped sharply within first 6 months, ranged from 49.4% (fibrates) to 66.8% (ARBs), and declined slowly afterwards. ANOVA analyses indicated that concomitant therapy and use of Consolidated Mail Outpatient Pharmacy (CMOP) were associated with better compliance and longer persistence in most drug classes (P<0.05), except ARBs (nonsignificant). CONCLUSIONS: Adherence with AD, AH, and LL therapy in veterans declines substantially over time. Adherence may be improved by initiating AD, AH, and LL concomitantly and use of CMOP.