OBJECTIVES: Higher healthcare costs are incurred by patients with MetS. WL may decrease the risk of MetS and its component comorbidities, thereby reducing medication use. PHEN/TPM ER treatment, combined with lifestyle interventions, can induce WL and reduce incidence of MetS. This post-hoc analysis of a PHEN/TPM ER study evaluated annual cost-offsets associated with changes in concomitant medication use among patients with MetS. METHODS: CONQUER randomized obese/overweight patients (BMI ≥27 -≤45kg/m) with ≥2 weight-related comorbidities to placebo (n=994), PHEN 7.5mg/TPM ER 46mg (7.5/46; n=498), or PHEN 15mg/TPM ER 92mg (15/92; n=995). MetS was defined as presence of ≥3 of the following risk factors: waist circumference ≥102cm (men), ≥88cm (women); triglycerides ≥150mg/dL; HDL-cholesterol <40mg/dL (men), <50mgl/dL (women); systolic blood pressure (BP) ≥130mmHg or diastolic BP ≥85mmHg; and fasting glucose ≥100mg/dL. This analysis included patients with MetS using ≥1 concomitant medication at baseline or end of treatment (EOT) for hypertension, dyslipidemia, or type 2 diabetes. Cost-offsets (±SD) in antihypertensive, lipid-lowering, and antidiabetic medication use were calculated by multiplying unit cost (Medi-Span's PriceRx) by number of doses per day from baseline to Week 56/EOT. PHEN/TPM ER cost was not included. RESULTS: In total, 349 patients receiving placebo, 184 receiving 7.5/46, and 359 receiving 15/92, had MetS at baseline and received ≥1 concomitant medication. At baseline, mean weight (±SD) was 105±18kg among all patients.  Baseline annual concomitant medication costs were $1222±1450, $1306±1401, and $1303±1348 for placebo, 7.5/46, and 15/92, respectively. At EOT, mean percent WL was -1.9%, -8.6%, and -10.5%, respectively (P<.0001 vs placebo). At EOT, annual concomitant medication costs increased with placebo and decreased with PHEN/TPM ER: $36±33 (+3%), -$83±46 (-6%), and -$103±33 (-8%), respectively (P<.05 vs placebo). CONCLUSIONS: These findings suggest that PHEN/TPM ER-enhanced WL is associated with a reduction in annual medication costs vs placebo in patients with MetS.