Systematic Reviews to Ascertain the Safety of Diabetes Medications
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Clinicians and patients with type 2 diabetes enjoy an expanding list of medications to improve glycemic control. With this expansion has come a flurry of concerns about the safety of these antihyperglycemic agents, concerns that affect judgments about the risk/benefit balance of therapy. Some of these safety signals have been identified through the synthesis of existing research evidence. Thus, it has become important for clinicians and clinical policymakers to understand the strengths and limitations of systematic reviews and meta-analyses in determining the safety of diabetes medications. In this paper, we highlight key safety concerns with diabetes medications and discuss the role evidence synthesis plays in each, with special attention to its strengths and limitations.
KeywordsSystematic review Meta-analysis Diabetes Safety Diabetes medications
This publication was supported by CCaTS Grant Number TL1 TR000137 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
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Conflict of Interest
Michael R. Gionfriddo declares that he has no conflict of interest. Oscar L. Morey-Vargas declares that he has no conflict of interest. Juan P. Brito declares that he has no conflict of interest. Aaron L. Leppin declares that he has no conflict of interest. M. Hassan Murad declares that he has no conflict of interest. Victor M. Montori declares that he has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Centers for Disease Control and Prevention. Increasing prevalence of diagnosed diabetes—United States and Puerto Rico, 1995–2010. Morb Mortal Wkly Rep. 2012;61:918–21.Google Scholar
- 4.Green S, Higgins JPT, Alderson P, Clarke M, Mulrow CD, Oxman AD. Chapter 1: Introduction. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from http://www.cochrane-handbook.org.
- 12.•Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170:1191–201. doi: 10.1001/archinternmed.2010.207. This meta-analysis included the largest trial of cardiovascular safety for rosiglitazone and confirmed an increased of myocardial infarction and heart failure associated with rosiglitazone use.PubMedCrossRefGoogle Scholar
- 13.•Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicenter, randomized, open-label trial. Lancet. 2009;373:2125–35. doi: 10.1016/s0140-6736(09)60953-3. This is the largest randomized trial looking at the cardiovascular safety of rosiglitazone and is at the center of the controversy surrounding the cardiovascular safety of rosiglitazone.PubMedCrossRefGoogle Scholar
- 14.Egger M, Smith GD, Altman D. Systematic reviews in health care: meta-analysis in context. London: BMJ books; 2008.Google Scholar
- 16.••Department of Health and Human Services. Advisory committee meeting for NDA 21071 Avandia (rosiglitazone maleate) tablet July 13 and 14, 2010. http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/ucm218491.htm. This document details the 2010 FDA review of rosiglitazone, within which the limitations of the RECORD trial are highlighted.
- 17.Food and Drug Administration. FDA requires removal of certain restrictions on the diabetes drug Avandia. November 25, 2013. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376516.htm.
- 20.•Murad M, Montori VM. Synthesizing evidence: shifting the focus from individual studies to the body of evidence. JAMA. 2013;309:2217–8. doi: 10.1001/jama.2013.5616. This paper expounds the reasons why clinicians should examine the body of evidence rather than individuals studies.PubMedCrossRefGoogle Scholar
- 27.Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomized controlled trial. Lancet. 2005;366:1279–89. doi: 10.1016/s0140-6736(05)67528-9.PubMedCrossRefGoogle Scholar
- 32.Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med. 2013;173:534–9. doi: 10.1001/jamainternmed.2013.2720.PubMedCrossRefGoogle Scholar
- 35.••Cohen D. Has pancreatic damage from glucagon suppressing diabetes drugs been underplayed? BMJ. 2013;346:f3680. doi: 10.1136/bmj.f3680. This is an investigative report written by an editor from the BMJ that highlights the concerns around the safety of glucagon supressing drugs.
- 37.Meinert CL. Clinical trials: design, conduct and analysis. New York, New York: Oxford University Press; 2012.Google Scholar
- 39.Meinert CL. Clinical Trials Dictionary: Terminology and usage recommendations. Hoboken, NJ: John Wiley & Sons, Inc.; 2012.Google Scholar
- 40.U.S. Food and Drug Administration. FDA’s Sentinel Initiative. 2013. http://www.fda.gov/Safety/FDAsSentinelInitiative/default.htm. Accessed 19 Sept 2013.