¹ Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
² Section of Cardiovascular Disease, Department of Experimental and Applied Medicine, University of Brescia, Italy
³ Nottingham Clinical Research Group (NCRG), Nottingham, UK
⁴ GlaxoSmithKline, USA
⁵ National Heart and Lung Institute, Imperial College London, UK
⁶ Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
⁷ Department of Cardiology, University of Hull, Kingston upon Hull, UK
⁸ Department of Cardiology, Ospedale di Cattinara, Trieste, Italy
⁹ Sticares Cardiovascular Research Foundation, Rhoon, Netherlands
¹⁰ F Hoffmann - La Roche, Basel, Switzerland and I. Medical Clinic, University Hospital Mannheim, University of Heidelberg, Germany

Correspondence to:
Correspondence to:
Professor C Torp-Pedersen
Department of Cardiology, Bispebjerg University Hospital, 2400 Copenhagen NV, Denmark; ctp{at}heart.dk

ABSTRACT
Background: ß 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.

Keywords: ß adrenergic receptor antagonists; carvedilol; diabetes mellitus; heart failure; metoprolol

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