Tools for Practice


#34 Rosiglitazone – Reasonable Option or Regrettable Choice?


CLINICAL QUESTION
Is rosiglitazone a reasonable second or third line agent in the management of Type 2 Diabetes (DM2)?

BOTTOM LINE
Strong evidence supports increased cardiovascular risk, specifically MI, in Type 2 Diabetes patients receiving rosiglitazone. In the absence of any demonstrated patient-oriented benefits, there is no indication for its use.


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EVIDENCE
A 2007 meta-analysis (42 randomized controlled trials, 27,847 patients) first assessed the impact of rosiglitazone on cardiovascular (CV) outcomes in DM2 patients.
  • Rosiglitazone caused a statistically significant increase in myocardial infarction (MI) over placebo or other drugs, Relative Risk Increase 43% (Confidence Interval (CI) 3%-97%). 1
    • No difference in cardiovascular deaths.
  • Some questioned the meta-analysis validity due to inclusion of low-quality studies and concern that analysis may have overestimated CV events.2
Two larger 2010 meta-analyses3,4 support the increased risk of MI with rosiglitazone
  • 56 trials, 35,531 patients Odds Ratio 1.28 (CI 1.02-1.63), Number Needed to Harm (NNH) 52 over five years. 3
  • 52 trials, 16,995 patients Odds Ratio 1.80 (CI 1.03-3.25). 4
    • FDA analysis4 found the researchers’ management of some data potentially masked rosiglitazone harms.
An FDA mandated re-analysis of the open-label, manufacturer-sponsored RECORD data did not find increased risk of MI (Hazard Ratio 1.13 (CI 0.80-1.59) or related outcomes with rosiglitazone. 5 Rosiglitazone is known to increase heart failure, Odds Ratio 1.93 (CI 1.30-2.93). 4 Context:
  • Rosiglitazone was approved based on its ability to improve glycemic control, without any evidence of improvement in patient-oriented outcomes.
  • A systematic review reported a strong link between author’s views on rosiglitzone and financial conflicts of interest with manufacturer. 6
  • The American Diabetes Association and the European Association for the Study of Diabetes released a consensus statement in 2009 recommending against the use of rosiglitazone in DM2. 7
  • In 2013, the FDA relaxed restrictions on rosiglitazone based on re-analysis of the RECORD trial, despite remaining concerns on its safety. 8,9
October 4, 2010

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Author(s):

  • Christina Korownyk MD CCFP
  • G. Michael Allan MD CCFP

1. Nissen SE, Wolski K. N Engl J Med. 2007; 356:2457-71.

2. Hlatky MA, Bravata DM. ACP Journal Club. 2007 Nov-Dec; 147:66.

3. Nissen SE, Wolski K. Arch Intern Med. 2010; 170(14):1191-1201.

4. Food and Drug Administration. Rosiglitazone cardiovascular safety meta-analysis: presented at the July 13-14, 2010 meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. Available from: https://wayback.archiveit.org/7993/20170405214642/https://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommi ttee/UCM224738.pdf. Last Accessed: January 13, 2018.

5. Mahaffey KW, Hafley G, Dickerson S, et al. Am Heart J. 2013; 166:240-9.

6. Wang AT, McCoy CP, Murad MH, et al. BMJ. 2010; 340:c1344.

7. Nathan DM, Buse JB, Davidson MB, et al. Diabetes Care. 2009; 32(1):193-203.

8. Tucker ME. BMJ. 2013; 346:f3769.

9. McCarthy M. BMJ. 2013; 347:f7144.

Authors do not have any conflicts of interest to declare.