Lorraine L. Lipscombe, MD, MSc
In patients with type 2 diabetes, is rosiglitazone (RGZ) as add-on therapy to metformin (MFN) or sulfonylurea (SFU) noninferior to MFN plus SFU for cardiovascular (CV) outcomes?
Randomized controlled trial (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes [RECORD]). ClinicalTrials.gov NCT00379769.
Blinded (outcome adjudication committee).*
Mean 5.5 years.
364 centers in 25 countries in Europe and Australasia.
4458 patients 40 to 75 years of age (mean age 58 y, 52% men) who had type 2 diabetes, body mass index > 25 (mean 31) kg/m2, and hemoglobin (Hb) A1c level > 7.0% to 9.0% (mean 7.9%) on maximum doses of MFN or SFU. Exclusion criteria included hospitalization for a major CV event in ≤ 3 months, planned CV intervention, and heart failure (HF).
RGZ, 4 mg/d, plus MFN or SFU, with starting doses determined by local practice (n = 2220); or MFN plus SFU (control) (n = 2227). Drug doses were increased after 8 weeks if the HbA1c target of ≤ 7.0% was not reached. Rescue therapy was used if HbA1c levels were ≥ 8.5% with maximum doses.
Primary outcome was a composite of hospitalization or death from CV causes. Secondary outcomes were all-cause death; CV death; myocardial infarction (MI); stroke; HF; other adverse events; and a composite of CV death, MI, or stroke. The upper noninferiority margin of the hazard ratio for the primary outcome was 1.20.
88% (intention-to-treat analysis).
RGZ plus MFN or SFU was noninferior to MFN plus SFU for the primary composite endpoint (Table). Risks for HF and bone fractures were greater in the RGZ group than in the control group (Table), but groups did not differ for the secondary composite endpoint (Table), its components, or all-cause death.
In patients with type 2 diabetes, rosiglitazone added to metformin (MFN) or sulfonylurea (SFU) was noninferior to MFN plus SFU for overall cardiovascular safety but increased risk for heart failure and fractures.
Rosiglitazone as add-on therapy to metformin or sulfonylurea (RGZ) vs metformin plus sulfonylurea (control) in type 2 diabetes†
†CV = cardiovascular; other abbreviations defined in Glossary. RRI, RRR, NNH, NNT, and CI calculated from hazard ratios in article.
‡Criterion for noninferiority was met because the upper limit of the CI for the hazard ratio was < 1.20.
Lipscombe LL. Rosiglitazone was noninferior to metformin plus sulfonylurea for CV events but increased risk for HF and fractures in type 2 diabetes. Ann Intern Med. ;151:JC4–8. doi: 10.7326/0003-4819-151-8-200910200-02008
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Published: Ann Intern Med. 2009;151(8):JC4-8.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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