Volume 16, Issue 11 p. 1165-1173
ORIGINAL ARTICLE

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls

C. A. Bannister

C. A. Bannister

The Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK

Cardiff School of Computer Science and Informatics, Cardiff University, Cardiff, UK

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S. E. Holden

S. E. Holden

The Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK

Global Epidemiology, Pharmatelligence, Cardiff Medicentre, Cardiff, UK

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S. Jenkins-Jones

S. Jenkins-Jones

Global Epidemiology, Pharmatelligence, Cardiff Medicentre, Cardiff, UK

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C. Ll. Morgan

C. Ll. Morgan

Global Epidemiology, Pharmatelligence, Cardiff Medicentre, Cardiff, UK

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J. P. Halcox

J. P. Halcox

Department of Cardiology, School of Medicine, Swansea University, Swansea, UK

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G. Schernthaner

G. Schernthaner

Department of Medicine, Rudolfstiftung Hospital Vienna, Vienna, Austria

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J. Mukherjee

J. Mukherjee

Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Wallingford, CT, USA

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C. J. Currie

Corresponding Author

C. J. Currie

The Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK

Global Epidemiology, Pharmatelligence, Cardiff Medicentre, Cardiff, UK

Correspondence to: Craig J. Currie, Professor of Applied Pharmacoepidemiology, The Cochrane Institute of Primary Care and Public Health, Cardiff University, The Pharma Research Centre, Cardiff Medicentre, Cardiff CF14 4UJ, UK.

E-mail: currie@cardiff.ac.uk

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First published: 07 July 2014
Citations: 280

Abstract

Aims

Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all-cause mortality in diabetic patients treated first-line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes.

Methods

We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first-line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables.

Results

We identified 78 241 subjects treated with metformin, 12 222 treated with sulphonylurea, and 90 463 matched subjects without diabetes. This resulted in a total, censored follow-up period of 503 384 years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person-years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy [survival time ratio (STR) = 1.0], adjusted median survival time was 15% lower (STR = 0.85, 95% CI 0.81–0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58–0.66) in diabetic patients treated with sulphonylurea monotherapy.

Conclusions

Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first-line therapy and implies that metformin may confer benefit in non-diabetes. Sulphonylurea remains a concern.