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Intensive “early” treatment was similar to national guidance-based treatment at preventing diabetes-related complications or heart disease over five years in this large trial.

General practices in the UK (49 practices), Netherlands and Denmark screened 135,000 asymptomatic adults aged 40 to 69 for type 2 diabetes before offering one of two treatment approaches. Intensive management was geared towards achieving targets for blood glucose, blood pressure and cholesterol levels by providing support for GPs, and protected time for delivering extra monitoring, healthy lifestyle advice and medication. The comparison group received standard diabetes care according to their respective national guidelines.

Five years on there were no significant differences in rates of cardiovascular deaths, strokes, heart attacks or other diabetes-related complications. This may in part be due to improved standards of care over time which could have reduced any difference between intensive management and care as usual. This study did not find that intensive management was cost-effective either in the short or long term, although researchers note the intervention costs may be cheaper now.

Efforts towards earlier detection and treatment of type 2 diabetes seem logical and are now part of routine practice. However, this large, well-designed NIHR-funded trial suggests some caution in assuming there are large improvements to be gained from intensive early management of diabetes detected at screening. Further analysis of this study and other relevant NIHR-funded research is given in a recent review of diabetes research.

Why was this study needed?

About 4 million people in the UK have diabetes (diagnosed or undiagnosed). In nine out of ten cases this is type 2 diabetes which in many people eventually causes heart disease. Type 2 diabetes can exist for many years without recognised symptoms and it has been argued that detecting it early and treating heart disease risk factors may prevent health complications.

The large blood vessels can become affected causing complications like heart attack and stroke. Affected smaller blood vessels can lead to eye disease, nerve and kidney damage.

Good diabetes management through a combination of physical activity, diet changes and medication to achieve target levels of blood pressure, cholesterol and sugar, can reduce the risk of complications. So, as well as detecting it earlier, intervening earlier might also help in the long-run.

This trial aimed to test these ideas. Whether early detection of type 2 diabetes through screening and intensive treatment would significantly improve the long-term health or prevent deaths in those who develop the condition.

What did this study do?

Between 2001 and 2006 this cluster randomised control trial asked 343 general practices in England, Denmark and The Netherlands to screen adults aged 40 to 69 for type 2 diabetes.

Around half the 3,057 newly diagnosed patients were assigned an intensive intervention while the other half received standard diabetes care according to their respective national guidelines.

The intensive intervention practices received education, more time and a small financial incentive to manage medications, diet and physical activity advice more aggressively, to achieve specific targets for blood glucose, blood pressure and cholesterol. These targets were informed by other trials, which suggested they would reduce risk of complications.

The cluster design of this trial means that practices rather than individuals were initially randomised to screening plus intensive intervention or screening plus routine care and is a practical way to answer this important question. The researchers were careful to assess whether the clustering process had introduced important differences between the groups, which it did not.

What did it find?

  • Prescription of medications to manage glucose, blood pressure and lipids increased in both groups, but was more common in the intensive treatment group (prescribed for an extra 10 to 30 patients per 100).
  • After an average of 5.3 years there were no significant differences between the groups in the number of first cardiovascular events including heart attack, stroke or revascularisation procedures. The combined rate of these events was about 14 per 1000 per year in the intensive treatment group compared with 16 per 1000 in the standard care group (combined hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65 to 1.05).
  • There was also no difference in the rate of death from any cause (HR 0.91, 95% CI 0.69 to 1.21). There were 12 deaths per 1000 per year in the intensive group compared with 13 per 1000 in the standard care group.
  • There were very small differences in the number of people with eye, nerve and kidney damage. But none achieved statistical significance.
  • Both groups reported similar levels of well-being, quality of life and satisfaction with their treatment.
  • Using just the UK data, intensive treatment cost around £981 per patient, including costs for materials, preparatory meetings, extra patient consultations and extra treatments. Screening plus intensive treatment was not found to be good value for NHS money in either short (up to five years) or long-term (up to 30 years) analyses.

What does current guidance say on this issue?

The NHS Health Check for adults aged 40 to 74 checks heart health, including risk factors for type 2 diabetes. Those found to be at risk are offered blood sugar testing. Some screening practices used in this trial were similar, but were generally more comprehensive.

In July 2014 the UK National Screening Committee did not recommended population screening of adults for type 2 diabetes as there was evidence this didn’t improve health outcomes. This decision is due for review in 2017/18 and is likely to consider the evidence in this trial.

NICE guidelines on management of type 2 diabetes in adults provide treatment targets and cover intensification of treatment in the form of adding more medication if the person’s condition is not responding. Achieving treatment targets for type 2 diabetes is a defined priority for commissioners in England partly achieved through the current health check programme. It is also highlighted in strategic policy in England, Wales, Northern Ireland and Scotland.

What are the implications?

Diabetes represents a large and growing public health issue, highlighting the need to improve efforts to prevent diabetes, such as through lifestyle and diet changes.

This trial covers two approaches that were not current NHS practice at the time – systematic type 2 diabetes screening of adults, and intensified target-driven diabetes management for those detected earlier than they would have been without screening. The lack of any clear evidence of benefits might have several explanations which suggest rushing to change practice is not needed.

The authors note the improvement in general quality of care for people with diabetes in general practice. This could mean that differences between intensive and standard treatment over time have become less marked. This improvement has been enhanced by the Quality and Outcomes Framework system of remuneration for general practitioners. It might have contributed to the fact that heart disease mortality in high-risk individuals in the control group was 50% lower than expected on the basis of observational data. Furthermore, the prevalence of undiagnosed diabetes might have been previously overestimated, also reducing the power of the trial to detect benefits of early diagnosis and treatment.

One theory as the trial began was that the time difference between detecting diabetes by screening and usual clinical diagnosis could be a determinant of better outcomes in screened practices. Recent estimates suggest this ‘lead time’ might be even shorter than the researchers expected (3 years) and that the benefits of screening might have been overestimated.

Plans to intensify treatments beyond current routine care should also consider feasibility and acceptability to patients.

Citation and Funding

Simmons RK, Borch-Johnsen K, Lauritzen T, et al. A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study. Health Technol Assess. 2016;20(64):1-86.

This project was funded by the National Institute for Health Research Technology Assessment Programme (project number 08/116/300).


Diabetes UK. Facts and stats. London: Diabetes UK; 2015.

NHS Choices. Type 2 diabetes. London: Department of Health; 2016.

NICE. Preventing type 2 diabetes: overview. NICE pathway. London: National Institute for Health and Care Excellence; 2016.

NICE. Type 2 diabetes in adults: management. NG28. London: National Institute for Health and Care Excellence; 2016.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre

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The interventions to promote intensive treatment in each centre aimed to educate and support general practitioners (GPs) and practice nurses in target-driven management (using medication and promotion of a healthy lifestyle) of hyperglycaemia, blood pressure and cholesterol. Actions were stepped (increased intensity with higher risk) and treatment targets and algorithms were the same for the intensive treatment groups in all centres.

  • GPs were advised to consider prescribing:

– an angiotensin-converting enzyme (ACE) inhibitor for patients with blood pressure ≥ 120/80 mmHg or a previous cardiovascular event

– 75 mg of aspirin daily to patients without specific contraindications.

  • Haemoglobin A1c (HbA1c) level target was under 7.0%. Alternations or additions to glucose-lowering therapy were initiated when HbA1c >6.5%. If HbA1c remained above 7.0% with oral agents, insulin therapy was initiated.
  • The treatment algorithm included a recommendation to prescribe a statin to all patients with a total cholesterol level of 3.5mmol/l or more.
  • The structured lifestyle education was dietary modification, weight loss, increased physical activity, smoking cessation and improving adherence to medication.
  • Diabetes nurses were trained in the management of the treatment algorithms and in providing lifestyle education. They were authorised to prescribe medication, supervised by the GPs. During the first year of the intervention, every three months a two-hour training session was arranged. Objectives of these sessions included discussing obstacles in reaching the target values, exchanging experiences, and evaluating cooperation with GPs. At least once per year, GPs from the intervention group were reminded about treating their ADDITION patients according to the protocol.

Although treatment targets were specified and classes of medication recommended, prescribing decisions, including choice of individual drugs, were made by practitioners and patients.


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