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Effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET)
  1. Christian Torp-Pedersen1,
  2. Marco Metra2,
  3. Andrew Charlesworth3,
  4. Phillip Spark3,
  5. Mary Ann Lukas4,
  6. Philip A Poole-Wilson5,
  7. Karl Swedberg6,
  8. John G F Cleland7,
  9. Andrea Di Lenarda8,
  10. Willem J Remme9,
  11. Armin Scherhag10,
  12. for the COMET investigators
  1. 1Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
  2. 2Section of Cardiovascular Disease, Department of Experimental and Applied Medicine, University of Brescia, Italy
  3. 3Nottingham Clinical Research Group (NCRG), Nottingham, UK
  4. 4GlaxoSmithKline, USA
  5. 5National Heart and Lung Institute, Imperial College London, UK
  6. 6Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
  7. 7Department of Cardiology, University of Hull, Kingston upon Hull, UK
  8. 8Department of Cardiology, Ospedale di Cattinara, Trieste, Italy
  9. 9Sticares Cardiovascular Research Foundation, Rhoon, Netherlands
  10. 10F Hoffmann - La Roche, Basel, Switzerland and I. Medical Clinic, University Hospital Mannheim, University of Heidelberg, Germany
  1. Correspondence to:
    Professor C Torp-Pedersen
    Department of Cardiology, Bispebjerg University Hospital, 2400 Copenhagen NV, Denmark; ctp{at}heart.dk

Abstract

Background: β Blocker treatment may worsen glucose metabolism.

Objective: To study the development of new onset diabetes in a large cohort of patients with heart failure treated with either metoprolol or carvedilol.

Design: Prospective and retrospective analysis of a controlled clinical trial.

Setting: Multinational multicentre study.

Patients: 3029 patients with chronic heart failure.

Interventions: Randomly assigned treatment with carvedilol (n = 1511, target dose 50 mg daily) or metoprolol tartrate (n = 1518, target dose 100 mg daily).

Results: Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, decreased glucose tolerance or hyperglycaemia) and new onset diabetes (clinical diagnosis, repeated high random glucose level or glucose lowering drugs) were assessed in 2298 patients without diabetes at baseline. Diabetic events occurred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.61 to 0.99; p = 0.039). New onset diabetes was diagnosed in 119/1151 (10.3%) v 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR = 0.78, CI 0.61 to 0.997; p = 0.048), respectively. Patients with diabetes at baseline had an increased mortality compared with non-diabetic subjects (45.3% v 33.9%; HR = 1.45, CI 1.28 to 1.65). Both diabetic and non-diabetic subjects at baseline had a similar reduction in mortality with carvedilol compared with metoprolol (RR = 0.85; CI 0.69 to 1.06 and RR = 0.82; CI 0.71 to 0.94, respectively).

Conclusion: A high prevalence and incidence of diabetes is found in patients with heart failure over a course of 5 years. New onset diabetes is more likely to occur during treatment with metoprolol than during treatment with carvedilol.

  • β adrenergic receptor antagonists
  • carvedilol
  • diabetes mellitus
  • heart failure
  • metoprolol

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Footnotes

  • Published Online First 18 January 2007

  • Competing interests: Andrew Charlesworth and Phillip Spark are employees of Nottingham Clinical Research Group that performed the statistical analyses of the trial. Mary Ann Lukas and Armin Scherhaug are employees of the sponsors of the study. All other authors have competing interest in the form of paid lectures and participation in advisory boards for numerous pharmaceutical companies.

    The COMET investigators are listed in a previous publication: Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet2003;:–13.

  • Ethical approval: This study was approved by all relevant ethical committees before initiation.

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