Diabetes treatment guidelines need revamping say researchers
Doctors should routinely consider giving cholesterol-lowering statins to anyone with diabetes who has a
substantial risk of a heart attack or a stroke, according to the authors of research to be published
tomorrow (Saturday 14 June ) in The Lancet medical journal1.
A UK multi-centre randomised trial of nearly 6,000 people with diabetes has provided the first definitive
evidence that statins cut the risk of heart attacks, strokes or revascularisation operations by about a third
in diabetic patients, irrespective of their cholesterol levels and whether or not they have existing arterial
These results mean that guidelines for treating diabetes should be revamped, with more emphasis placed
on reducing blood cholesterol levels in all people with diabetes. If the findings are acted on, around one
million people with diabetes in the UK and 100 million worldwide2 will be candidates for cholesterol-
lowering treatment. This could prevent at least 10,000 heart attacks, strokes and revascularisation
operations each year in the UK, and about one million worldwide.
The research, involving 69 UK hospitals, was coordinated by the Clinical Trial Service Unit of Oxford
University. The 6,000 diabetic patients were among 20,000 volunteers at high risk of heart attacks and
strokes who took part in the Medical Research Council/British Heart Foundation Heart Protection Study
(HPS), the overall results of which were published last year (6 July) in The Lancet. The new report
extends and amplifies the analyses of the large group who had diabetes.
Of the nearly 6,000 patients with known diabetes in the study, 90% had Type 2 diabetes and 10% had
Type 1 diabetes3. About 2,000 had pre-existing coronary disease, 1,000 had other occlusive arterial
disease and 3,000 had no evidence of either condition. Lowering cholesterol with 40mg daily of
simvastatin (the study statin) was effective in all types of diabetic patient, and was similarly effective
whatever the patients age, sex or cholesterol level.
Lead researcher Professor Rory Collins said: There are estimated to be more than one million people in
the UK with diabetes mellitus and about 150 million worldwide, and those figures are expected to double
by 2025. People with diabetes have a higher risk of heart attacks and strokes than the general population,
and most of their deaths are due to cardiovascular disease. So, these new results are extremely important,
not only for the very many people who have diabetes but also for the health systems that have to cope
with this increasing global problem.
Overall in the study, about 25% of patients who were allocated placebo (dummy) tablets experienced at
least one major vascular event (heart attack, stroke or revascularisation procedure) during 5 years of
treatment. Allocation to 40mg daily simvastatin produced an average reduction in bad LDL-cholesterol
of 1mmol/L during the study, and reduced this rate of major vascular events by about one quarter.
Diabetic patients who did not have any diagnosed occlusive arterial disease had a major vascular event
rate of about 15% in the placebo group, but simvastatin still reduced this somewhat lower event rate by
about one quarter .
Even among those diabetic patients whose bad LDL cholesterol would have been considered relatively
low (below 3.0 mmol/L), there was a reduction in risk of about one quarter. The proportional risk
reduction was also about a quarter among various other categories of diabetic patient including those
with different duration, type or control of diabetes, the over 65s, those with raised blood pressure and
those with total cholesterol below 5.0mmol/L. In addition, among those who had a first major event after
entering the study, being allocated simvastatin reduced the rate of subsequent events during the 5-year
The clinical co-ordinator of the study, Dr Jane Armitage, said: When we make allowances for those
volunteers who did not comply fully with their study treatments, daily use of 40mg simvastatin would
probably reduce the rate of first vascular events by about one-third. So, five years of treatment in diabetic
patients without any occlusive arterial disease would prevent around 45 out of every 1,000 people with
diabetes from suffering at least one major vascular event, and would prevent about 70 first or subsequent
events among these 45 individuals.
Professor Collins said that it is now imperative for diabetes treatment guidelines to be re-examined. Our
finding that lowering blood cholesterol levels with statin therapy produces substantial reductions in the
risk of heart attacks and strokes in diabetic patients together with the findings in two other studies5 that
blood pressure lowering treatment can do likewise has important implications for avoiding the vascular
complications of diabetes. In particular, these results support a renewed emphasis on controlling blood
cholesterol and other vascular risk factors, in addition to controlling hyperglycaemia, among people with
He added: As drug patents expire on different brands of statins, these drugs are becoming much cheaper
and will be affordable in many more countries around the world.6
Professor Sir Charles George, Medical Director at the British Heart Foundation, said: Its very exciting
that this huge study which the BHF helped to launch was able to focus on around 3,000 people with
diabetes but no previous evidence of coronary heart disease or other diagnosed arterial disease. The
finding that simvastatin was effective in all types of diabetic person has important implications for statin
treatment, which must now be considered in all diabetic people with an additional risk factor for coronary
Sir George Radda, Chief Executive of the MRC, said: This is excellent news, another important finding
from the Heart Protection Study, this time for those with diabetes. Its very timely as the recent
Department of Health/MRC Review into diabetes research outlined the need to define the most
appropriate and cost effective therapies in relation to cardiovascular disease in diabetics.
Simon O'Neill, Head of Care Developments, Diabetes UK, said: "This research proves that statins can
offer real benefits to many people with diabetes, helping them to avoid some of the life threatening
complications of diabetes - heart attack and stroke. We hope that all health care professionals will take
this research into account when treating people with diabetes. Many people could benefit greatly if
offered statins as an integral part of their diabetes care programme."
Dr Sue Roberts, the UKs National Clinical Director for Diabetes, said: "This important research, which
was carried out in the UK, proves that taking statins can make a significant improvement to the health of
people with diabetes. It is yet another piece of evidence that prevention really can work and should be
available to everyone who can benefit.
Reducing the risk of heart and blood vessel disease by planning individual care is one of the first targets
in the Diabetes NSF, and I want to ensure that the lessons of this research are acted upon everywhere as
quickly as possible. Cholesterol will also be measured routinely to monitor how well the message is
getting across, and to check that improvement is happening everywhere for as many people as possible.
The Heart Protection Study was funded by the UK Medical Research Council, the British Heart
Foundation,7 Merck & Co (makers of simvastatin) and Roche Vitamins. The study was designed,
conducted and analysed entirely independently of all funding sources by the
Clinical Trial Service Unit.
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 5,963 people with diabetes:
a randomised placebo-controlled trial. The Lancet. 14 June 2003. Vol 361. No. 9374 Pp 2005-16
King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025. Diabetes Care 1998; 21: 1414-31
Diabetes Mellitus: a condition characterised by a raised concentration of glucose in the blood because of a
deficiency in the production and/or action of insulin. Type1 (juvenile onset diabetes) involves a severe deficiency or
absence of insulin production. Type 2 (maturity onset diabetes) involves reduced insulin production and usually
starts after the age of 40.
Results in more detail available from Wednesday 11 June on web site:
UK Prospective Diabetes Study Group (UKPDS). Tight blood pressure control and risk of macrovascular
and microvascular complications in type 2 diabetes. BMJ 1998; 317: 70313. The Heart Outcomes Prevention
Evaluation Study Investigators (HOPE). Effects of an angiotensin-converting enzyme inhibitor, ramipril, on
cardiovascular events in high risk patients. N Engl J Med 2000:342: 14553
Simvastatin is now out of patent in the UK and some other European countries, although it remains under
patent protection in the USA until 2005. Currently, 40mg daily simvastatin (Zocor) has a list price in the UK of
1.06 per day, but generic simvastatin is anticipated to cost only about 10-25 pence per day (i.e. one-tenth to one-
quarter of current prices).
More information can be obtained about MRC at www.mrc.ac.uk and
about BHF at www.bhf.org.uk
Mark Corbett: Tel: +44 (0)1865 404805