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The British Journal of Diabetes & Vascular Disease Metformin
European Association for the Study of Diabetes, Amsterdam, The Netherlands, September 2007
British Journal of Diabetes & Vascular Disease 2007 7: 247 The online version of this article can be found at: can be found at:
The British Journal of Diabetes & Vascular Disease
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Metformin – life begins at 50
A symposium held on the occasion of the 43rd Annual Meeting of the
European Association for the Study of Diabetes, Amsterdam, The Netherlands,
September 2007.
Edited by meeting chairman: Professor IW Campbell, Victoria Hospital, Kirkcaldy and University of St Andrews.
Introduction
Figure 1.
Demonstration of the antihyperglycaemic action of metformin Metformin has been in toms of diabetes (together
in 1961.5 The administration of metformin to normoglycaemic subjects, or subjects with well controlled diabetes, induced little change on blood glucose. Hyperglycaemic patients, by contrast, demonstrated a marked reduction in blood glucose after administration of metformin Fasting blood glucose (mmol/L)
Hours post-dose
Reproduced with permission. ‘Metformin, The Gold Standard. A Scientific Handbook’, eds Bailey CJ et al. Wiley, Chichester, UK 2007;288. Copyright Metformin through five
decades – historical
perspective
VOLUME 7 ISSUE 5 . SEPTEMBER/OCTOBER 2007 Abbreviations
Figure 2. Risk of adverse outcomes with or without metformin
treatment in diabetic patients within the PRESTO trial.9 Type 2 diabetic patients undergoing coronary revascularisation were stratified retrospectively for receipt (n=887) or non-receipt (n=1110) of metformin (patients receiving European Association for the Study of Diabetes lipodystrophy syndrome associated with human immunodeficiency virus infection metformin
MI, death and revasculation
for ischaemia (p=0.005)
Myocardial infarction (p=0.002)
Death (p=0.007)
Ischaemia-driven
revascularistion (p=NS)
Acronyms
Adjusted odds ratio (95% CI)
Prevention of Restenosis with Tranilast and its Outcomes trial Prospective Pioglitazone Clinical Trial In Macrovascular Events trial United Kingdom Prospective Diabetes Study Actions of metformin –
treating the
pathophysiology of type
2 diabetes
THE BRITISH JOURNAL OF DIABETES AND VASCULAR DISEASE Multiple actions of metformin on sources of increased Source of increased Action of metformin
cardiometabolic risk
Blood glucose (as effective as other oral antidiabetic classes) Hepatic glucose productionPeripheral glucose utilisation Anti-atherogenic in animals or cultured cells Vasculoprotective
benefits of metformin in
reducing cardiovascular
Metformin – benchmark
for oral antidiabetic
VOLUME 7 ISSUE 5 . SEPTEMBER/OCTOBER 2007 Figure 3. Glycaemic benefit from combining metformin with a DPP-IV
inhibitor18 or a GLP-1 analogue.19 Both trials were randomised,double-blind, placebo-controlled studies of additional therapy Disease area
Evidence base
Indication Potential future
in patients uncontrolled on metformin alone Sitagliptin
(24 weeks)
Placebo (n=224)
Sitagliptin (n=453)
Mean change fr
baseline in HbA
Exenatide
(30 weeks)
Placebo (n=113)
Key: NAFLD = non-alcoholic fatty liver disease; NASH = non-alcoholic Exenatide 5 mg (n=110)
steatohepatitis; HIV-LD = lipodystrophy syndrome associated with human Exenatide 10 mg (n=113)
immunodeficiency virus infection; PCOS = polycystic ovary syndrome.
Mean change fr
baseline in HbA
All changes on active treatment
were p<0.001 versus placebo
Metformin – therapeutic
potential beyond
diabetes
Metformin – core
therapy in management
guidelines for type 2
diabetes worldwide
THE BRITISH JOURNAL OF DIABETES AND VASCULAR DISEASE Figure 4. Summary of the joint ADA-EASD management algorithm for
Key messages
Lifestyle intervention + metformin
● Jean Sterne first gave metformin to type 2 diabetic patients 50 years ago, in Paris after the serendipitous Metformin
discovery of effects on blood glucose during attemptsto treat influenza and other conditions with ● Metformin counters insulin resistance (especially in liver and muscle) through a range of biological actions which are modest individually, but substantialcollectively ● Metformin improves vascular structure and function, and has been shown to improve cardiovascular outcomes in a prospective, randomised study (UKPDS)and in retrospective analyses of clinical outcome Key: * = TZD + insulin is contraindicated in some countries. Reproduced ● Metformin is as effective as other agents on reducing with permission Bailey et al. Br J Diabetes Vasc Dis 2006;6:148.
hyperglycaemia and can be combined with any otherantidiabetic agent, including insulin ● Guidelines already recommend metformin for diabetes prevention and the management of PCOS; potential uses in other insulin-resistant states (NAFLD, HIV lipodystrophy), and for the prevention of cancer are ● Current guidelines, including those from the EASD and the ADA, recommend early and intensive antihyperglycaemic intervention based on metformin together with lifestyle intervention and other agents 2004;21:115-17.
Conclusions
References
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Correspondence to:
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This symposium was sponsored by an educational grant from Merck Serono Limited. The chairman would like to thank Dr Mike Gwilt for assiting in preperation of this manuscript.
The views expressed in this report are not necessarily those of the British Journal of Diabetes and Vascular Disease or Merck Serono Limited.
2007 British Journal of Diabetes and Vascular Disease and MediNews (Diabetes) Limited. All rights reserved.
THE BRITISH JOURNAL OF DIABETES AND VASCULAR DISEASE

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