Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity

Inclusion Criteria: * Age 40 to 75 years * Male or postmenopausal female * BMI ≥ 30 kg/m2 * One or more major cardiovascular (CV) risk factors (hypertension, dyslipidemia, impaired glucose tolerance OR metabolic syndrome) Exclusion Criteria: * Congestive heart failure * Renal impairment * History of bariatric surgery (i.e. lap-band, Roux-en-Y or biliopancreatic diversion) * Type I diabetes mellitus * Weight loss \> 10% in the past 6 months * Recurrent nephrolithiasis * Current treatment for seizure disorder * Hepatic cirrhosis * Current use of study medications * Current use of oral estrogen * History of smoking cessation in the past three months * Current cholestasis or malabsorption syndrome * Planned use of any herbal or over-the-counter supplements for weight loss * History of allergic reactions to metformin, topiramate, orlistat or any of ingredients * Medical conditions requiring continuous use of phosphodiesterase inhibitors and/or the inability to withhold phosphodiesterase inhibitors for 48 hours * Participation in another clinical drug study within four weeks prior to this investigation. * Participation in any other weight loss or rigorous exercise program. * Any disease or condition that in the opinion of the investigator may interfere with completion of the study