Montreal, Canada, 20 October 2009 – New results from ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), the largest clinical trial ever performed in patients with type 2 diabetes worldwide, provide important insights into the therapeutic strategy to adopt for efficient and safe blood glucose control aimed at the reduction of severe diabetes complications.¹

The new data from ADVANCE, presented today at the International Diabetes Federation (IDF) Congress, show that the efficacy and safety of intensive blood glucose control using gliclazide modified release (MR) (Diamicron MR)-based regimen is maintained across a broad range of patients in different clinical settings.¹

ADVANCE demonstrated that intensive glucose control with a gliclazide MR–based treatment regimen in people with type 2 diabetes reduces the combined risk of microvascular and macrovascular events, primarily through reductions in the risk of diabetic nephropathy.²

“Intensive glucose control with a gliclazide MR-based regimen was effective in lowering HbA_1C, irrespective of age, duration of diabetes, sex, body mass index, or HbA_1C at study entry, and also irrespective of initial glucose lowering treatment,” said ADVANCE Study Investigator Sophia Zoungas from The George Institute for International Health, Australia. “The gliclazide MR-based regimen was well-tolerated with very low rates of severe hypoglycemia and no weight gain.”

ADVANCE showed a positive trend toward a reduction of major cardiovascular events in diabetes patients who received intensive glucose control.² This finding was supported in a recent collaborative meta-analysis of 4 trials of intensive glucose lowering, including ADVANCE and ACCORD, which demonstrated a significant 9% reduction in major cardiovascular events, primarily reflecting a 15% reduction in myocardial infarction.³ On the basis of observational data, several national registers (including more than 70,000 patients with type 2 diabetes), have recently reported that glucose lowering regimens that included gliclazide were associated with lower risks of mortality compared to other therapeutic strategies.^4,5

“ADVANCE is a huge reservoir of valuable clinical information,” concluded ADVANCE Principal Investigator Professor John Chalmers from The George Institute for International Health, Australia. “For this reason, we plan to continue the follow-up of the ADVANCE patients and we believe that this new study—ADVANCE-ON⁶— will play a pivotal role in defining future clinical management of the tens of millions of people with type 2 diabetes worldwide.”

Additional new data

At the IDF Congress, the ADVANCE investigators also provided important insights into factors predicting cardiovascular risk in this population.⁷

Age at diagnosis, known duration of diabetes, sex, pulse pressure, treated hypertension, atrial fibrillation, retinopathy, HBA_1C, albumin/creatinine ratio, and non-HDL cholesterol level at baseline were all found to be significant predictors of cardiovascular events. A new risk prediction tool was developed by the ADVANCE investigators using these variables, paving the way for a new ‘risk engine’ that may be more relevant for contemporary populations of treated patients with diabetes compared to older risk prediction tools such as the Framingham and UKPDS (United Kingdom Prospective Diabetes Study) models.⁷


References

1. Chalmers J, Zoungas S, Ninomiya T, et al. New results from ADVANCE. IDF Congress Invited Talk, 22 October 2009. Montreal, Canada.
2. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2572.
3. Turnbull F, Abraira C Anderson R Byington R Chalmers J et al. Intensive glucose control,and macrovascular outcomes in type 2 diabetes. Diabetologia, ePub ahead of print, 05 August 2009
4. Schramm TK. Eur Heart J. 2009;30(suppl):304. Abstract ESC Congress 2009.
5. Khalangot M et al, Diabetes Res Clin Pract. 2009 Sep 29. [Epub ahead of print]
6. Zoungas S, Patel A, Neal B, et al. ADVANCE-ON: a post-trial observational study. Oral presentation, IDF Congress, 21 October 2009. Montreal, Canada.
7. Kengne AP, Patel A, Colagiuri S, et al. Derivation of the ADVANCE models for predicting the risk of major cardiovascular disease in people with diabetes. Oral presentation, IDF Congress, 20 October 2009. Montreal, Canada.

12 March 2009 – A new analysis from the largest study of type 2 diabetes treatments has shown that while atrial fibrillation (irregular heart beat) is relatively common in patients with type 2 diabetes and substantially increases risk of death, these patients can be better protected against death by intensive blood pressure lowering treatment. The findings are published today in the European Heart Journal.

Atrial fibrillation (AF) is a common type of arrhythmia, or irregular heart beat. AF is commonly observed in diabetic patients, who are at least twice as likely to experience the condition. Researchers found that patients with type 2 diabetes with AF had up to 77% increased risk of dying, but this was significantly reduced when clinicians treated patients with a combination blood pressure lowering drugs, (perindopril and indapamide).

“Our new analysis confirms that among patients with type 2 diabetes, those with atrial fibrillation are at substantially higher risk of death. This study informs clinicians that AF, or an irregular heart beat is a marker of greater risk of cardiovascular events and death among diabetics. Such patients should have their cardiovascular risk factors, such as blood pressure and cholesterol, controlled more aggressively,” said study leader, Professor Anushka Patel, from The George Institute for International Health.

An estimated 250 million people are living with diabetes around the world, and this number is projected to increase to 380 million at 2025. Researchers anticipate that around 40 million of these will also have AF.

The ADVANCE (Action in Diabetes and Vascular Disease) study included 11,140 patients from 20 countries and was initiated and designed by Australia’s George Institute for International Health. This new analysis aimed to investigate serious clinical outcomes associated with AF and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF, among individuals with type 2 diabetes.

“We estimate that five years of active treatment would prevent one death among every 42 patients with AF and one death among every 120 patients without AF,” added Professor Patel.

Prof Patel pointed out that AF was frequently undetected in diabetic patients. “The current analysis highlights the importance of actively evaluating diabetic patients for the presence of AF, to identify those at particularly high risk of cardiovascular events. Routine administration of blood pressure-lowering treatment, as well as greater use of antiplatelet or anticoagulant agents and statins, may be expected to reduce the incidence of a broad range of adverse outcomes in these patients.”

22 February 2009 – A combination of two blood pressure lowering treatments has significantly reduced the risk of kidney disease among patients with type 2 diabetes. The findings, reported by The George Institute for International Health reveal that blood pressure lowering is beneficial to all patients with diabetes, even for patients with normal blood pressure levels.

An estimated 250 million people are living with diabetes around the world. Kidney disease is a common (more than half of type 2 diabetes patients develop renal impairment) and devastating complication of diabetes - up to 20% of people with diabetes die of renal failure.

"Our research demonstrated that lowering blood pressure with an ACE inhibitor/diuretic combination reduces the risk of kidney complications by 20%, and even resolves some early manifestations of kidney disease in people with diabetes, regardless of whether their blood pressure is normal or elevated," said co-author, Dr Vlado Perkovic, The George Institute for International Health.

The key findings of the paper, published in the Journal of the American Society of Nephrology, shows that this treatment has wide benefits for all patients with type 2 diabetes. "For all people with diabetes, reducing their risk of kidney disease is imperative. Individuals who develop kidney disease are at significantly increased risk of developing cardiovascular complications, which is the major cause of death in these patients," added Dr Perkovic.

The ADVANCE (Action in Diabetes and Vascular Disease) study was initiated and designed by Australia’s George Institute for International Health and involved a group of independent medical researchers from 20 countries worldwide. This new analysis aimed to examine the effects of blood pressure lowering on kidney disease in people with diabetes and a broad range of blood pressure levels.

ADVANCE involved 11,140 patients with type 2 diabetes who were treated and followed up for five years. One group received a combination of two antihypertensive (blood pressure-lowering) drugs: the angiotensin-converting enzyme (ACE) inhibitor perindopril and the diuretic drug indapamide. The other group received inactive placebos.

ADVANCE treatment strategy has potential to save lives and protect millions of diabetics worldwide from serious complications

ROME, Italy, 8 September 2008 – According to new data presented today at the European Association for the Study of Diabetes (EASD) congress, combining intensive blood sugar control based on gliclazide modified release (Diamicron MR®) with intensive blood pressure lowering based on a fixed combination of perindopril and indapamide (Preterax®) can reduce the risk of death from heart disease by nearly one quarter (24%) and the risk of kidney complications by one third (33%) in patients with type 2 diabetes.

These latest results from ADVANCE (Action in Diabetes and Vascular Disease), the largest ever trial performed in patients with type 2 diabetes, provide further evidence for a new therapeutic strategy with the potential to save lives and protect millions of diabetics worldwide from serious complications.

The new ADVANCE results show that the benefits of tight blood glucose control and blood pressure lowering are both independent and fully additive. This new evidence represents an important step forward for the management of millions of people with diabetes worldwide, as the treatment strategy used in ADVANCE reduced both the likelihood of developing and dying from the complications of diabetes.

Intensive and progressive blood glucose control for long term benefits
These latest combined findings follow the recent publication of the results from the glucose lowering arm of the study in the New England Journal of Medicine.1 These results showed that an intensive strategy including first systematically prescribing the sulfonylurea gliclazide modified release, up to the maximal dose of 4 tablets per day, and then progressively other conventional drugs, lowers blood glucose levels safely to hemoglobin A1c levels of 6.5% and protects patients against the serious complications of diabetes.
In particular, this intensive strategy reduced the risk of kidney disease by one-fifth, and reduced the risk of proteinuria, a potent predictor of increased cardiovascular risk, by nearly one third (30%).
These results go beyond existing evidence, and could potentially benefit millions of patients worldwide, since renal disease is one of the most serious and disabling consequences of diabetes, leading to death in one in five people with diabetes.
The intensive strategy based on modified release gliclazide provided all these benefits with a low risk of hypoglycemia (4 times less compared to previous studies) and no weight gain in contrast with other therapeutic strategies based on early and higher use of insulin as well as glitazones, as shown in ACCORD. 2

Today, it is clear that the prevention of the serious complications of diabetes requires multi-factorial intervention, since the new ADVANCE results show that the benefits of intensive blood glucose and blood pressure lowering are independent and fully additive in reducing cardiovascular death (-24%) and renal complications (-33%). In this context, an intensive and progressive glucose control strategy as chosen in ADVANCE can play an important role, in particular in protecting the kidneys.

ADVANCE
ADVANCE was initiated and designed by the researchers at Australia’s George Institute for International Health and co-sponsored by the Australian government’s National Health and Medical Research Council, and Servier. The multicenter, randomized, placebo controlled study involved a total of 11,140 patients with type 2 diabetes from 20 countries worldwide with a five year follow-up.

The choice of Diamicron MR was based on its well known efficacy and safety profile, as proven by millions of diabetic patients treated every day.


References:
1. The ADVANCE collaborative Group. Intensive blood glucose control and vascular outcomes in patients with Type 2 Diabetes. N Engl J Med 2008;358:2560-72.
2. The ACCORD study Group. Effects of Intensive Glucose Lowering in type 2 Diabetes. N Engl J Med 2008;358:2545-59.

“ADVANCE results go beyond existing evidence”

San Francisco, USA, 6 June 2008 – New results from the world’s largest ever study of diabetes treatments show that intensive blood glucose (sugar) control using modified release gliclazide and other drugs as required, protects patients against serious complications of the disease. In particular, intensive treatment reduces the risk of kidney disease by one-fifth. Presented today at the American Diabetes Association and published in the New England Journal of Medicine, the results of ADVANCE (Action in Diabetes and Vascular Disease) show that this intensive treatment strategy has the potential to benefit millions of diabetic patients worldwide.

Diabetes mellitus is one of the greatest threats to the health of populations worldwide. Globally, there are approximately 250 million people with diabetes and that number is estimated to rise to 380 million in 2025.

Chief investigator of the study, Professor Stephen MacMahon, Principal Director of The George Institute, Australia said "We are facing a global epidemic of diabetes. The ADVANCE results go beyond existing evidence as we have now shown that reducing the haemogloboin A1c level (a marker of blood glucose control) to 6.5% is a safe and effective way to reduce serious complications, particularly the risk of kidney disease, one of the most serious and disabling consequences of diabetes, leading to death in one in five people with diabetes.”

“Hypoglycemia (low blood sugar) was uncommon in the ADVANCE study, although as expected it was more frequent among those receiving intensive treatment,” pointed out Study Director, Associate Professor Anushka Patel from The George Institute. “These findings reinforce that blood glucose lowering in diabetes is safe and has an important role to play in the prevention of serious complications.”

“Moreover, in contrast to the recently halted ACCORD study, there was no evidence whatsoever of any increased risk of death among those receiving intensive treatment in ADVANCE.”

ADVANCE was initiated and designed by physicians at Australia’s George Institute for International Health and involved a group of independent medical researchers from 20 countries worldwide. The study involved 11,140 patients with type 2 diabetes who were treated and followed up for five years. The study aimed to reduce levels of haemogloboin A1c to 6.5% or below. Intensive treatment included the sulfonylurea, modified-release gliclazide, for all patients and other drugs as required to achieve the haemoglobin target.

The major findings of ADVANCE show that intensive blood glucose lowering treatment:
• Safely controlled blood glucose to a mean HbA1c level of 6.5%
• Significantly reduced the overall risk of serious diabetes complications (by 10%), with a one-fifth reduction in kidney disease (21%) and 30% reduction in the development of proteinuria, a well established marker of increased cardiovascular risk.
• Achieved a positive trend towards reduction in the risk of cardiovascular death (12%), although not statistically significant.

“Today, it is clear that the prevention of major vascular complications of diabetes requires a multi-factorial approach addressing all modifiable risk factors” concluded Professor John Chalmers, chairman of the study management group, “among which an intensive glucose control plays an important role, in particular in protecting the kidneys”.

“ADVANCE will have huge implications for care of patients worldwide”

19 May 2008 – ADVANCE (Action in Diabetes and Vascular Disease), the largest clinical trial ever performed in patients with type 2 diabetes worldwide, is now complete. The second and final part of this five-year trial investigates the effect of intensive blood glucose lowering treatment on major macrovascular (cardiovascular death, MI, stroke) and microvascular (kidney and eye disease) events.

Over 11,000 patients were randomised and more than 20 countries participated in ADVANCE. The final patient visits were made at the end of January 2008, the database is now closed and main analysis complete. The data from the blood glucose lowering arm of ADVANCE will be presented for the first time at the American Diabetes Association Scientific Sessions on 6 June 2008 in San Francisco, USA.

Globally, there are approximately 250 million people with diabetes, most of who will eventually be killed or disabled by the complications of their condition. It is estimated that by 2025 the number of individuals with diabetes will rise to 380 million. The most common cause of death in people with diabetes is heart disease. Kidney disease also affects a large proportion. In 2006, the United Nations issued a statement calling for increased international action to combat the global epidemic of diabetes.

“People with diabetes have a two to four-fold greater risk of experiencing a cardiovascular event compared to non-diabetics. However, despite this high risk, there is surprisingly little evidence about the role of intensive blood glucose control in the prevention of diabetic vascular disease”, points out the ADVANCE Principal Investigator Professor John Chalmers from The George Institute for International Health, Sydney.

“ADVANCE will provide new and robust evidence on whether intensive glucose lowering treatment improves outcomes and could have huge implications for the practical management of type 2 diabetes worldwide”, says ADVANCE Study Director Associate Professor Anushka Patel also from The George Institute.

ADVANCE was designed to answer two questions: first, does intensive treatment to lower blood pressure improve outcome; and second, does intensive treatment to reduce blood glucose improve outcome. The first question was answered by the results of the blood pressure lowering arm of the study in which a treatment regimen including the fixed combination of the ACE inhibitor perindopril and the diuretic indapamide was shown to reduce mortality in patients with diabetes. The results of glucose-lowering arm, (based on gliclazide modified release, MR and a range of other drugs) of the ADVANCE study will provide the answer to the second question when announced later this year.

ADVANCE was conducted in 215 clinical centres selected from Australasia, Asia, Europe and North America. The trial randomised 11,140 high risk type 2 diabetes patients and the primary end-point was a composite of major macro vascular (cardiovascular death, MI, stroke), and micro vascular complications (kidney and eye disease).

In the intensive glucose lowering arm of the study, patients received 1 – 4 tablets of gliclazide MR (30 – 120 mg) daily together with other glucose control medications. The aim of this regimen was to achieve a haemoglobin A1c (HbA1c), a measure of glucose control, of = 6.5%. Treatment was continued until the completion of follow-up (five years).

Due to the early release of results by another similar large trial of diabetes patients, in February the ADVANCE Data Safety Management Board announced that interim results from ADVANCE provided no evidence of safety issues among patients receiving the intensive glucose control regimen. The study was accordingly closed out according to the planned schedule. The full results of ADVANCE will define the overall balance of benefits and risks of intensive glucose lowering treatment.

The ADVANCE study was designed and conducted by an independent collaborative group of medical researchers co-sponsored by The George Institute for International Health at the University of Sydney, the National Health & Medical Research Council of Australia and Servier International.

Preliminary findings from the largest-ever study of treatments for diabetes provide no evidence that intensive treatment to lower blood glucose (sugar) increases risk of death

Interim results from the ADVANCE Study, involving 11,140 high-risk patients with type 2 diabetes, provide no evidence of an increased risk of death among those patients receiving intensive treatment to lower blood glucose (sugar).

These findings contrast with those reported last week by the US National Heart Lung and Blood Institute suggesting that intensive glucose lowering treatment levels had increased the death rate among patients with diabetes recruited to the ACCORD trial.

ADVANCE was designed to answer two questions in patients with type 2 diabetes: first, does intensive treatment to lower blood pressure improve outcome; and second, does intensive treatment to reduce blood glucose improve outcome.

In September 2007, the ADVANCE Collaborative Group published evidence in The Lancet showing that the blood pressure lowering treatment had reduced the death rate among participants. In January 2008, the part of the study designed to assess the effects of the intensive treatment to reduce blood glucose was completed. As in ACCORD, this intensive treatment program was designed to lower blood glucose to levels below those usually recommended by clinical guidelines.

Chairman of the ADVANCE Data Monitoring and Safety Committee, Professor Rory Collins from the University of Oxford, said “The interim results from ADVANCE provide no confirmation of the adverse mortality trend reported from the ACCORD study.” He also noted that the ADVANCE interim results were based on more than twice as much data and similar levels of glucose control as in ACCORD. The members of the Data Monitoring and Safety Committee are the only members of ADVANCE study team with access to the study results.

ADVANCE principal investigator, Professor Stephen MacMahon from The George Institute for International Health in Sydney, stated that “Due to the unexpected report from the ACCORD trial, we felt it was in the public interest for us to ask our Data Monitoring and Safety Committee to make a statement as to whether the available data from ADVANCE provide any support for the suggestion that intensive blood glucose lowering may increase mortality.”

In ADVANCE, the intensive blood glucose lowering program aimed to reduce levels of haemoglobin A1c (a marker of long term blood glucose control) to below 6.5%. This treatment regimen included a sulfonylurea drug, gliclazide modified release, for all patients and a range of other drugs for those not reaching target blood glucose levels.

ADVANCE commenced in July 2001 and patients were treated and followed-up for an average of five years. The Data Monitoring and Safety Committee, comprising a panel of independent experts in the field, met every six months to review the study data for any safety issues or other concerns.

ADVANCE Management Committee Chairman, Professor John Chalmers, commented “Doctors and patients should feel reassured that the mortality trend reported by the ACCORD study has not been found in the interim results from ADVANCE. However, we need to await more definitive analyses and reports from both studies before drawing final conclusions”.

“Final patient visits have been completed, and the ADVANCE study data base is close to finalisation. We expect to have definitive results soon,” said Study Director, Dr Anushka Patel, from The George Institute. “At this stage, the Data Monitoring and Safety Committee have reviewed results that are more than 99% complete, so we are confident that the interim findings communicated here are a reliable guide to the final results”.

ADVANCE was conducted by an independent collaborative group of medical researchers, with support from the National Health & Medical Research Council of Australia and the Paris-based, Institute de Recherche Internationales Servier.

VIENNA, Austria, 2 September 2007 – The routine administration of a fixed combination of perindopril and indapamide (Preterax) improves survival and reduces coronary and renal events in diabetics, according to the results of the blood-pressure-lowering arm of the landmark, five year ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) study presented today at the European Society of Cardiology (ESC) meeting1, and published online in The Lancet.

ADVANCE is the first and largest trial ever performed with a fixed combination antihypertensive in type 2 diabetic patients. The multicentre, randomised, placebo controlled study involved a total of 11,140 patients with type 2 diabetes from 20 countries worldwide. Patients included were both normotensive and hypertensive and were already receiving most of the usual treatments provided to patients with diabetes, including other blood- pressure lowering drugs.

ADVANCE showed that Preterax significantly reduces total mortality by 14% and the risk of cardiovascular death by 18%. In absolute terms, one death would be avoided for every 79 patients treated with Preterax for five years. In addition, patients receiving Preterax achieved a significant 14% reduction in total coronary events and a 21% reduction in renal events. That means that one coronary event would be avoided for every 75 patients treated with Preterax for five years and one renal event would be avoided for every 20 patients treated with Preterax for five years.

“The results of ADVANCE should have major implications for guidelines, clinical care and public policies”, says co-principal study organiser Professor Stephen MacMahon from The George Institute for International Health, Sydney Australia. He adds, “These results represent an important step forward in health care for the millions of people with diabetes worldwide. This treatment reduced the likelihood of dying from the complications of diabetes by almost one-fifth, with virtually no side-effects.”

Preterax was chosen for the ADVANCE trial for its efficacy in treating the alterations in both large arteries and the microcirculation which commonly occur in hypertensives and diabetics. Moreover, Preterax achieves a strong blood pressure lowering efficacy, specific benefits on cardiac perfusion and protection of the heart and kidney.
Globally, there are approximately 250 million people with diabetes, most of who will eventually be killed or disabled by the complications of their condition. The most common cause of death in people with diabetes is heart disease. Kidney disease also affects a large proportion. In 2006, the United Nations issued a statement calling for increased international action to combat the global epidemic of diabetes.

“Diabetes is emerging as one of the greatest 21st century threats to the health of populations worldwide. The health gains seen in the ADVANCE study have been obtained in addition to the benefits provided by patients’ existing treatment. If the benefits seen in ADVANCE were applied to just half the population with diabetes worldwide, more than a million deaths would be avoided over five years. There is now a case for considering routine treatment with Preterax for patients with type 2 diabetes”, comments Professor John Chalmers, ADVANCE co-principal investigator also from the George Institute for International Health.

The ADVANCE study was initiated and designed by the investigators and co-sponsored by The George Institute for International Health and the University of Sydney, and Servier. A second arm of the study, that sets out to assess the risks and benefits of intensive glucose lowering using a gliclazide MR-based regimen (Diamicron MR) will report later.

Preterax and Diamicron MR are registered products of Servier.

24 May 2007 -- ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), a landmark, six-year trial has now closed the part of the study that aims to investigate the effect of Preterax, a blood pressure lowering agent containing a fixed -dose combination of the ACE inhibitor perindopril and the diuretic indapamide, on the risk of macro- and micro- vascular complications in patients with type 2 diabetes mellitus. The data from this blood pressure component of ADVANCE will now be analysed and submitted at this year's European Society of Cardiology meeting (1 - 5 September 2007).

Diabetes mellitus is emerging as one of the greatest threats to the health of populations worldwide. Globally, it has been estimated that the number of individuals with diabetes will rise from 171 million in 2000 to 366 million in 2030. It is associated with increased risks of micro vascular complications, including retinopathy, nephrophy and neuropathy. It also increases the risks of macro vascular diseases, including coronary heart disease, stroke and peripheral vascular disease.

ADVANCE is the largest clinical trial ever performed in patients with type 2 diabetes, involving over 11,000 randomised patients worldwide, and will provide important information about the separate and joint effects of blood pressure lowering using Preterax, and intensive blood glucose lowering using a gliclazide-based (Diamicron MR) regimen, compared with standard care in a broad cross-section of high-risk individuals with type 2 diabetes.

The ADVANCE study was initiated and designed by investigators at The George Institute for International Health, and received funding from the National Health and Medical Research Council of Australia and from Servier, the makers of Preterax and Diamicron MR.

"People with diabetes have a two to four-fold greater risk of experiencing a cardiovascular event compared to non-diabetics. However, despite this high risk, there is surprisingly little recent evidence from randomised clinical trials on the role of blood pressure lowering in the prevention of diabetic vascular disease", points out the ADVANCE study chairman John Chalmers from The George Institute. "ADVANCE will provide new evidence about the effects of blood pressure lowering and glucose lowering which could have huge implications for the practical management of type 2 diabetes."

On a daily basis for three months, study patients received either one tablet of Preterax (2.0 mg perindopril / 0.625 mg indapamide) or a placebo, on top of any existing therapy such other blood pressure lowering drugs, or statins to lower cholesterol. After three months, the dose was doubled (4.0 mg / 1.25 mg). Treatment was continued until the completion of follow-up (5.5 years).

The multicentre, placebo-controlled study was conducted in 215 clinical centres selected from Australasia, Asia, Europe and North America. The trial randomised 11,140 type 2 diabetics aged 55 or over who had a high risk of vascular disease. There are two primary study outcomes - a composite of major macro vascular complications (stroke, MI, cardiovascular death), and a composite of major micro vascular complications (eye and renal disease).