The goal of this clinical trial is to understand if genetic variations are associated with the amount of weight loss with diet and while taking an FDA-approved medication for weight loss. The main question\[s\] it aims to answer are:
* In Aim One, the investigators propose to rigorously test the hypothesis that presence of the Taq1A A1+ polymorphism is associated with greater weight loss with NB compared with the A1- genotype.
* In Aim Two, the investigators will explore other genetic polymorphisms that might influence the efficacy of NB such as the fat mass and obesity-associated (FTO) gene which modulates DRD2 signaling, as carriers of risk alleles in both the FTO and ANKK1 gene demonstrate altered responses to reward-learning tasks associated with negative outcomes.
Participants will be in the study for 40 weeks, which consists of two phases:
1. From baseline to week 12, participants will receive individual nutritional counseling on a calorie restricted diet. This phase includes in-person visits, blood tests, an EKG, vital signs, questionnaires, body weight, and nutritional visits.
2. From week 12 to week 40, participants will continue to receive dietary counseling and will receive treatment with naltrexone/bupropion for 28 weeks. This phase includes in-person and phone visits, blood tests, vital signs, questionnaires, body weight, and nutritional visits.