OBJECTIVES: Over two-thirds of the US population are overweight or obese.  While current pharmacotherapy options for weight loss are limited, new weight loss products have not been approved partly over safety concerns, including some linked to weight-related illnesses such as hypertension.  However, very little is known about the association of available weight-loss pharmacotherapy with changes in drug therapy for weight-related illnesses. METHODS: A retrospective cohort analysis of a deidentified pharmacy claims database evaluated adult patients initiating weight-loss pharmacotherapy (no weight-loss drug prescriptions 6 months prior) between November 1, 2007 – October 31, 2010. Patients with continuous eligibility for 6 months pre- (baseline) and 6 months post- weight-loss drug initiation were evaluated for changes in concomitant drug therapy associated with weight-related illnesses (hypertension, dyslipidemia, type 2 diabetes, anxiety, gastrointestinal disorders, depression, and hypothyroidism).   Six-month outcomes included concomitant therapy incidence, and net change (% patients adding ≥1 drug minus % discontinuing ≥1 drug in each illness category) analyzed using t-test (significance at p<0.05). RESULTS: A total of 91,160 patients initiated weight-loss pharmacotherapy: phentermine (N=67,434), sibutramine (N=13,438), orlistat (N=8,047), phendimetrazine (N=4,631), and diethylpropion (N= 4,350); mean±SD age 44±12 years (96%, 18-64 y/o), 82% female.  Patients received 1.5±0.8 concomitant weight-related illness drugs at baseline for hypertension (21.6%) depression (14.9%), dyslipidemia (11.5%), hypothyroidism (9.2%), gastrointestinal disorders (9.6%), anxiety (6.7%), and diabetes (5.5%).  Incident/net therapy change over 6 months for each illness category: hypertension (3.2%/-6.5%), depression (0/-16.0%), dyslipidemia (1.1%/-12.2%), hypothyroidism (1.2%/+0.7%), gastrointestinal disorders (0.2%/-17.1%), anxiety (1.1%/-19.4%), and diabetes (0.6%/-8.9%).  All net changes from baseline are significant (p<0.05), with the exception of hypothyroidism therapy. CONCLUSIONS: Concomitant therapy for obesity-related illnesses generally has a low incidence and declines significantly over 6 months after initiating weight-loss pharmacotherapy. Antihypertensive and hypothyroidism therapy appear to follow different patterns, and whether this reflects disease progression, effect of weight-loss therapy, genetics, or other factors warrants further investigation.