Metformin in Heart Failure Observations PDF

O N L I N E L E T T E R S alerted metformin manufacturers that a after patents expire—in stark contrast to OBSERVATIONS label change was appropriate. Over the the recent thiazolidinedione labe...

O N L I N E L E T T E R S alerted metformin manufacturers that a after patents expire—in stark contrast to OBSERVATIONS label change was appropriate. Over the the recent thiazolidinedione label changes, ensuing months, the prescribing informa- which were widely disseminated. tion for all generic products was updated, Metformin in Heart eliminating the HF contraindication. In SILVIO E. INZUCCHI, MD1 November 2006, the final package insert FREDERICK A. MASOUDI, MD, MSPH2 Failure (Glucophage) was likewise modified. DARREN K. MCGUIRE, MD, MHSC3 For years, the wisdom of metformin’s From 1Yale University, New Haven, Connecticut; HF contraindication had been chal- the 2Denver Health Medical Center, Denver, Colo- W e recently learned of an impor- tant change in the prescribing lenged, since it was essentially based on rado; and the 3University of Texas, Southwestern case reports in the absence of clinical trial Medical Center, Dallas, Texas. information for metformin, pre- Address correspondence to Silvio E. Inzucchi, viously contraindicated in patients with validation and since glucose-lowering MD, Endocrinology, LLCI-101, Yale University type 2 diabetes accompanied by heart fail- options for such patients were otherwise School of Medicine, New Haven, CT 06520-8020. ure (HF) requiring pharmacological ther- limited. Moreover, there was biological E-mail: [email protected]. apy. The contraindication was introduced plausibility of benefit, particularly in pa- This letter is being simultaneously published in Downloaded from http://diabetesjournals.org/care/article-pdf/30/12/e129/595352/zdc0120700e129.pdf by guest on 29 November 2024 tients with insulin resistance (4). The re- 2007 in Diabetes Care and the American Heart Jour- to the label soon after the drug’s U.S. nal. Copyright 2007 by the American Diabetes As- release, when case reports emerged of cent FDA endorsement increases the oral sociation, Inc., and Elsevier. HF patients taking metformin who de- pharmacotherapy choices in HF patients DOI: 10.2337/dc07-1686 veloped lactic acidosis. It was never with diabetes. Renal dysfunction and © 2007 by the American Diabetes Association. clear, however, whether either the HF metabolic acidosis remain contraindica- tions; HF is still in the label’s “Warnings” or the medication were contributing section; it should obviously not be used in References factors. Subsequent analyses revealed a 1. Misbin RI: The phantom of lactic acidosis miniscule risk of lactic acidosis associ- those with acute or unstable symptoms. due to metformin in patients with diabe- ated with metformin therapy, as com- We bring this information to your tes. Diabetes Care 27:1791–1793, 2004 pared with that of an earlier biguanide, readership’s attention because we our- 2. Masoudi FA, Inzucchi SE, Wang Y, phenformin (1). selves were surprised to hear of this major Havranek EP, Foody JM, Krumholz HM: In 2005, two studies (2,3) sug- label change, with significant implica- Thiazolidinediones, metformin, and out- gested that metformin was safe and may tions for patient care. After discussions comes in older patients with diabetes and also provide advantages in the very pa- with our colleagues, it was clear that we heart failure. Circulation 111:583–590, tients in whom the drug was not to be were not alone in our ignorance. We con- 2005 used. These observational studies found ducted an informal poll of 118 endocri- 3. Eurich DT, Majumdar SR, McAlister FA, nologists and diabetes educators 10 Tsuyuki RT, Johnson JA: Improved clini- significantly lower mortality risks in cal outcomes associated with metformin type 2 diabetic patients treated with months after the label change was final- in patients with diabetes and heart failure. metformin compared with other agents, ized; of 101 respondents, 95 (94%) were Diabetes Care 28:2345–2351, 2005 after adjustment for differences in pa- similarly unaware. This episode raises 4. Masoudi FA, Inzucchi SE: Diabetes melli- tient mix. With this information, the concerns regarding clinician notification tus and heart failure. Am J Cardiol 99: Food and Drug Administration (FDA) when prescribing information is updated 113B–132B, 2007 DIABETES CARE, VOLUME 30, NUMBER 12, DECEMBER 2007 e129