Two drugs can be better than one when one counteracts the other’s side effects. A recent study shows a way to predict molecular interactions that make this possible. Ravi Iyengar of Icahn School of Medicine at Mount Sinai and coworkers also determined that side effects of tens of thousands of other drugs might be mitigated in a similar way (Sci. Transl. Med. 2013, DOI: 10.1126/sci translmed.3006548). Their work suggests that this is a strategy drug companies might want to pursue. The researchers probed FDA’s publicly accessible database of adverse drug interactions to find drugs that might reduce the relatively high incidence of heart attacks in patients taking GlaxoSmithKline’s diabetes drug rosiglitazone. The search revealed that patients who take both rosiglitazone and another diabetes drug, Amylin Pharmaceuticals’ exenatide, experienced significantly fewer heart attacks than other rosiglitazone users. Computational modeling enabled the team to predict the biomolecular target interaction that enables exenatide to exert its mitigating effect, and they confirmed that mechanism in mouse studies. Further analysis by the group showed that more than 19,000 other drug combinations might be similarly beneficial.