INTRODUCTION: Lifestyle modification through incorporation of exercise-training could improve metabolic syndrome (MetS) clinical components (hypertension, dyslipidemia, hyperglycemia and visceral abdominal obesity). We aimed to assess if long-term exercise-training could restrain the increased pharmacological cost of the clinical management of the MetS. METHODS: Medicine cost analysis during a 5-yr long randomized controlled exercise-intervention trial. Following a per-protocol analysis a group of 64 individuals 53 +/- 2 years old, with overweight (BMI 33.4 +/- 0.9 kg/m2) and MetS (3.6 +/- 0.2 factors) were randomized to a training (4 months.year-1 for 5-yr; Exercise, n = 25) or to a control group (Control, n = 26). Subjects were studied on three occasions during the five-year follow-up. Participants continued their routine medication managed by their general practitioner. The main outcome is the 5-yr evolution of medication cost to treat MetS (hyperglycemia, hypertension, and hyperlipidemia). A secondary outcome is the benefit-cost ratio of the exercise intervention. RESULTS: In Control, medicine cost increased 160% from baseline (p < 0.001) while in Exercise it remained unchanged (33%; p = 0.25). After 5-yr follow-up, medicine use was 60% and medicine cost 74% higher in Control than Exercise (p < 0.05 in both cases). However, MetS Z-score was similarly reduced over time in both groups (p = 0.244 for group x time interaction). The number of prescribed medications increased after 5-yr in Control (89%; p < 0.001) while it remained stable with yearly training (17%; p = 0.72 in Exercise). Ten-year atherosclerotic cardiovascular disease (ASCVD) risk estimation increased only in Control (15%; p = 0.05 for group x time interaction). The benefit in medicine savings (153 per year and patient) triplicated the estimated cost (50.8 per year and patient) of the exercise intervention. CONCLUSIONS: A 5-yr long supervised exercise-training program in middle-aged individuals with metabolic syndrome prevents the need for increasing medicine use. The savings in pharmacological therapy outweighs the estimated costs of implementing the exercise program.

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