The present invention relates generally to weight loss compositions and more particularly to orally administrable weight loss compositions for supporting weight loss in a subject in need thereof. Specifically, the present invention relates to compositions and methods comprising various combinations of orlistat and substances selected from methylxanthines, extracts of Morus sp., chromium polynicotinate, hydroxycitric acid or derivatives of hydroxycitric acid, flavanols, and yohimbine or derivatives of yohimbine.