In response to a 2008 FDA recommendation, drug manufacturers have been investigating cardiovascular outcomes associated with new diabetes drugs. While early evidence is promising, James Flory, MD, MSCE, notes that most of trials focus on classes of medications approved since 2005—including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Flory, from the Department of Healthcare Policy and Research at Weill Cornell Medical College in New York City, believes the work will shed needed light on the heart-related effects of these treatments; but he notes that it offers no additional insight on the cardiovascular safety of older drugs. Because the body of evidence supporting cardiovascular protections is limited for metformin, sulfonylureas, and other long-established medicines but is growing for newer agents, the more recent therapies are gaining favor in clinical practice. Flory suggests that FDA can address this weighted, but not necessarily warranted, preference for newer diabetes drugs by revising its guidelines for assessing the cardiovascular profile of these treatments. Active-controlled study designs, he suggests, should take precedence over placebo-based research. "Further," he argues, FDA "should consider indicating that it would be unlikely to approve indications for cardiovascular benefit for new diabetes drugs unless the agents have been compared with metformin as well as placebo in studies with cardiovascular outcomes."