Diabetes mellitus and obesity have become increasingly prevalent problems worldwide. Unfortunately, with traditionally prescribed glucose-lowering medications most individuals with diagnosed diabetes do not achieve and maintain adequate glycemic control over time; it may be even more challenging to lower blood glucose to an appropriate level without inducing a significant associated weight gain. Exenatide and rimonabant are recently developed agents that have demonstrated benefit in both glucose lowering and reduction of body weight. These medications may well prove to be attractive alternatives or additions to our more established diabetes therapies; however, these drugs have a side-effect profile that may limit their applicability to certain populations.