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The studies listed below are all major, multicentre trials in prediabetes or diabetes which included at least 1000 patients. Studies are sorted below according to their primary objective.

DPP
The Diabetes Prevention Program (DPP) was conducted in the United States and examined the effects of intensive lifestyle modification or treatment with metformin vs placebo on the development of diabetes in 3234 subjects with prediabetes. Published in 2002, results showed that lifestyle modification reduced progression to diabetes by 58%, while metformin treatment reduced diabetes progression by 31%. Both treatments were significantly better than placebo.

NAVIGATOR
The Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study is an international, randomised, multicentre trial including 9400 patients with prediabetes and CVD or CV risk factors, from over 40 countries. Patients will be randomly assigned to receive either placebo or nateglinide, and then either placebo or valsartan in a secondary randomisation. The study is divided into two phases, the first of which will assess progression to Type 2 diabetes, while the second will evaluate the effects of nateglinide and valsartan on CV outcomes. The diabetes prevention phase of the trial should be completed in 2006; the CV outcomes phase is due to finish in 2007.  

Glucose Control

ADOPT
A Diabetes Outcome Progression Trial (ADOPT) is an ongoing trial involving over 4300 patients at over 400 sites throughout North America and Europe. The trial is designed to show whether monotherapy with rosiglitazone, metformin, or glyburide will affect the progression of Type 2 diabetes, b-cell function, or cardiovascular risk markers in the early stages of Type 2 diabetes. The primary outcome of the trial is time to monotherapy failure, defined as a confirmed fasting plasma glucose above 10 mmol/L, and secondary outcomes include glucose control, b-cell function, CV risk markers, and quality of life. The trial is due to be completed in 2006.

DCCT
The Diabetes Control and Complications Trial (DCCT) was the largest, most comprehensive Type 1 diabetes study ever conducted. In this study, 1441 patients with Type 1 diabetes were randomly assigned to intensive therapy with multiple injections of insulin per day or conventional therapy, consisting of 1 or 2 injections per day. At endpoint, A1C in the intensive group was 7.3%, compared with 9.1% in the conventional group (P<0.001); and intensively treated patients saw risk reductions for microvascular endpoints of 54% to 63%. This site gives a comprehensive analysis of the DCCT and includes a slide show of the trial results.

DCCT/EDIC
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) is an observational study being conducted with the original study population of the DCCT. In EDIC, patients from both the intensive and conventional insulin treatment groups of the original study have been encouraged to undertake intensive insulin therapy. To date, key findings have shown that A1C values in the two groups have converged, but patients who were originally in the intensive therapy group continue to experience lower rates of complications.

UKPDS
The United Kingdom Prospective Diabetes Study (UKPDS) site is the official information resource for the landmark study in Type 2 diabetes, which involved 5102 patients and showed that intensive therapy significantly reduced the risk of any diabetes endpoint by 12% (P<0.03), of any microvascular complication by 25% (P<0.01), and of myocardial infarction by 16% (P=0.052). An epidemiologic analysis of the original study population is ongoing, and new data are still being published. On this site, the results are presented in a variety of formats, including an executive summary and a set of 100 slides; FAQs arising from the data are answered by the lead investigators.
 

ACCORD
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study is an ongoing study in which 10,000 adults with Type 2 diabetes will be enrolled from 70 clinics in the United States and Canada. Patients will be randomly assigned to a treatment regimen involving either aggressive or standard control of blood sugar. Then, depending on their blood pressure and cholesterol levels, they will be assigned to study arms that examine the effects of treatment on hypertension or lipids. The study is scheduled to run through 2009.

BARI 2D
The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) is an ongoing, randomised, multicentre trial designed to assess 5-year mortality rates in patients with Type 2 diabetes and documented, stable coronary artery disease (CAD). All 2300 patients in the trial will receive intensive blood pressure and lipid control. In addition, half these patients will be randomly assigned to undergo a revascularisation procedure for CAD, while the other half will receive medical treatment for CAD. Within each of these groups, the patients will be further subdivided into those randomly assigned to insulin-sensitising therapy with metformin or a thiazolidinedione, or to an insulin-augmenting strategy involving the oral secretagogues or insulin. Follow-up is expected to continue through 2007.

Look AHEAD
The Action for Heath in Diabetes trial, also known as the Look AHEAD trial, is an ongoing multicentre trial in the United States. Its aim is to examine the long-term effects on cardiovascular outcomes of an intensive lifestyle intervention programme to achieve and maintain weight loss in overweight volunteers with Type 2 diabetes. A control group will be given standard diabetes support and education. The study is designed to last 11.5 years and involve approximately 5000 patients. Results should be available in 2012.

ORIGIN
The Outcome Reduction with Initial Glargine INtervention (ORIGIN) trial is a multinational, ongoing study involving 10,000 patients that is designed to show whether treatment with insulin glargine can reduce cardiovascular morbidity and mortality in individuals with a high risk for vascular disease and either prediabetes (impaired fasting glucose of impaired glucose tolerance) or early Type 2 diabetes. Participants will be randomly assigned to treatment with either glargine or standard oral agent therapy; in the glargine group, a target fasting glucose of <5.3 mmol/L will be used as the basis for a structured low-dose algorithm. Patients in the oral agent group will undergo stepwise therapy according to ADA guidelines. In a secondary double-blind randomisation, the effects of omega-3 fatty acids (fish oil) will also be compared with placebo.

PROactive
The Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) study is a recently completed international, multicentre, double-blind, placebo-controlled trial to assess whether the addition of pioglitazone to an existing diabetes regimen will prevent macrovascular events in Type 2 diabetes. A total of 5238 patients with Type 2 diabetes and existing macrovascular disease participated in the trial. The primary endpoint of the study was the composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation. Addition of pioglitazone reduced the composite risk of these events by a nonsignificant 10%. The secondary endpoint, consisting of risk of all-cause mortality, nonfatal MI, and stroke was significantly reduced among patients in the pioglitazone group by 16%. The risk of nonfatal heart failure and edema was significantly increased, however. Patients receiving pioglitazone also experienced significant improvements in blood pressure levels by 3 mmHg and A1C levels by 0.5%, as well as positive effects on HDL and triglyceride levels.

RECORD
The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) is an ongoing, international, multicentre, double-blind trial with the goal of determining whether the addition of rosiglitazone to either metformin or sulfonylurea therapy is superior to the combination of metformin with a sulfonylurea, both in terms of glucose control and in preventing cardiovascular complications. The trial involves 3966 patients and is due to be completed in 2009. No online resources are available for this study at this time.


Hypertension and Diabetes

IDNT
The Irbesartan Diabetic Nephropathy Trial (IDNT) examined the rates of cardiovascular events among 1715 patients with Type 2 diabetes and overt nephropathy from over 200 centres in the Americas, Europe, Israel, and Australia. Patients were randomly assigned to treatment with an angiotensin receptor blocker (irbesartan), a calcium channel blocker (amlodipine), or placebo, in addition to ongoing antihypertensive treatment. Results were published in 2003 and showed that treatment with amlodipine significantly lowered patients’ risk of myocardial infarction compared with placebo (P=0.02), while irbesartan significantly lowered the risk of congestive heart failure when compared with either placebo (P=0.048) or amlodipine treatment (P=0.004).

MICRO-HOPE
The Heart Outcomes and Prevention Evaluation (HOPE) study included a substudy of diabetes patients known as the Microalbuminuria, Cardiovascular, and Renal Outcomes (MICRO)-HOPE study. This analysis comprised 3577 persons aged 55 years or older with diabetes, who were randomly assigned to receive either the angiotensin converting enzyme (ACE) inhibitor ramipril or placebo and vitamin E or placebo in a two by two factorial design. The results, published in 2000, showed that treatment with ramipril significantly lowered the risk of a cardiovascular event, by 25% (P=0.0004).

UKPDS
In addition to glucose control, the landmark United Kingdom Prospective Diabetes Study (UKPDS) trial also examined the effects of intensive blood pressure control in Type 2 diabetes, showing that the overall risk of microvascular complications was reduced by 37% (P<0.01) and of diabetes-related death by 32% (P<0.02). Additional study results, slides, and other information can be found on this website.


Dyslipidemia and Diabetes

AFORRD
The Atorvastatin in Factorial with Omega-3 fatty acids Risk Reduction in Diabetes (AFORRD) study is a one-year, multicentre, randomised, placebo-controlled trial to evaluate coronary heart disease risk reduction by a statin (atorvastatin) and/or omega-3 fatty acids. The trial will include 1000 people with Type 2 diabetes in the UK, and will assess the use of patient-centred techniques aimed at improving compliance as well as the effect of the medications. Study results should be announced in 2005.

CARDS
The Collaborative Atorvastatin Diabetes Study (CARDS) was a multicentre, randomised, placebo-controlled trial aimed at determining whether treatment with a statin (atorvastatin) would prevent cardiovascular disease in patients with Type 2 diabetes. The trial was conducted among 2838 patients in the UK and Ireland; none of the patients had any signs or symptoms of existing cardiovascular disease. Results, published in August 2004, demonstrated that treatment with the statin reduced the rate of death by 27%.

 

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