In the medical management of obesity, treating physicians observe significant heterogeneity in responses to pharmacotherapy. Indeed one of the most important clinical questions in obesity medicine is whether we can predict how an individual will respond to a particular pharmacotherapeutic agent. The present study examines patterns and predictors of weight loss among overweight and obese women who demonstrated early robust response to twice daily exenatide treatment. 182 women were assigned using single-blind randomization to either treatment with twice daily exenatide injections or to matched placebo injections with dietary counseling. Women who demonstrated > 5% weight loss after 12 weeks of treatment were deemed high responders and remained on study treatment for up to 52 weeks; women who lost < 5% body weight at 12 weeks were deemed low responders and stopped study treatment. We additionally characterized individuals who lost > 10% of body weight as super responders. Our primary outcome was change in body weight; secondary outcomes included changes in metabolic parameters including lipids, waist circumference, resting energy expenditure, and response to a meal tolerance test. We also performed an exploratory metabolomic analysis.