Changes in labelling for metformin use in patients with type 2 diabetes and heart failure: documented safety outweighs theoretical risks

been theorized that metformin could cause the accumulation of lactate under certain metabolic conditions such as the substantial tissue hypoperfusion and hypoxia observed in patients with acute heart failure. Although lactic acidosis can be fatal, current evidence indicates that any risk associated with metformin itself is minimal. Indeed, a recent systematic review of metformin use in type 2 diabetes with over 70 000 patient-years of followup demonstrated no cases of fatal or nonfatal lactic acidosis, although specific effects in those with heart failure were not assessed. Despite the fact that this contraindication has prevailed for years, the 2008 Canadian Diabetes Association Clinical Practice Guidelines recommended metformin as a first-line therapy in patients with type 2 diabetes and heart failure. In addition, despite Health Canada’s highly cautionary labelling, more than half (58%) of patients with diabetes and heart failure in Canada are currently prescribed metformin. Although the reasons for the widespread off-label use of metformin in diabetic patients with heart failure is unknown, it is likely attributable to the general level of comfort clinicians have with the long history of metformin use in Canada, coupled with the lack of certainty about the actual potential risk of lactic acidosis despite the cautionary labelling. In September 2009, Health Canada approved changes to product monographs for metformin that explicitly remove the contraindication in patients with heart failure. Since then, many of the major manufacturers of metformin in Canada (10 out of 18) have updated their product monographs to reflect this change. However, these product monographs still include a warning against metformin’s use in patients with acute, worsening heart failure, despite the fact that there is no evidence to support this concern. What new evidence has arisen to bring Health Canada’s labelling in line with current guidelines and clinical practice? In the absence of direct head-to-head trials evaluating metformin against other oral hypoglycemic agents in patients with heart failure, evidence for the downgrade in warning comes from observational studies. Specifically, 2 reports published in 2007 4,5 were cited in the revised product monographs, and 6 additional observational studies 6–11 confirmed the same findings: metformin is as safe or safer with respect to all adverse events than other oral glucose-lowering therapies in patients with both diabetes and heart failure. Given that these are observational rather than randomized controlled studies, it is difficult to say with certainty that metformin is actually advantageous in heart failure. However, observational studies are the most appropriate Changes in labelling for metformin use in patients with type 2 diabetes and heart failure: documented safety outweighs theoretical risks