NPC Archive Item: Intensive interventions in type 2 diabetes reduce mortality

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Gaede P, Lund-Andersen H, Parving H-H, et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. NEJM 2008:358:580–91

What is the background to this?
People with type 2 diabetes are at increased risk of cardiovascular disease (CVD) events compared with those without the condition. As we have recently blogged, the currently available evidence suggests that interventions addressing CV risk reduction can reduce microvascular and macrovascular complications in people with type 2 diabetes, whilst the benefits of tight blood glucose alone are much less. We blogged yesterday about the worrying ACCORD data which showed an adverse effect of tight blood glucose control.

This randomised controlled trial in 160 Danish patients with type 2 diabetes and microalbuminuria assessed whether a target driven, intensive multifactorial intervention would reduce the death from any cause and from CVD, compared with conventional treatment consistent with Danish national guidelines. The intensive intervention included tight control of blood pressure, blood glucose and lipids, use of renin-angiotensin system blockers for microalbuminuria, low-dose aspirin and behaviour modification (see below for details of actual targets).

What does this study claim?
The study found that, during 13.3 years follow-up, 30% of patients in the intensive therapy group died, compared with 50% in the conventional therapy group (absolute risk reduction [ARR] 20%; hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.32 to 0.89; P=0.02). Death from CVD was also lower in the intensive therapy group (ARR 13%; HR 0.43, 95%CI 0.25 to 0.67; P=0.04).

So what?
The point estimates in this small study (but with a long period of follow up) have a wide margin for error. But a 50% death rate over 13.3 years among patients receiving conventional treatment highlights the poor prognosis for patients with type 2 diabetes and microalbuminuria. This study has demonstrated that intensive multifactorial interventions can reduce the risk of dying from any cause or from CVD. Based on data from patients in the UK Prospective Diabetes study, and using a risk calculator, the authors think that statins and antihypertensive drugs might have the largest effect in reducing cardiovascular risk, with hypoglycaemic agents and aspirin being the next most important interventions. We would put smoking cessation (where appropriate) ahead of all of those.

As we keep saying, clinicians and patients should be aware of the importance of managing cardiovascular risk factors in patients with type 2 diabetes. This may include encouraging smokers to stop smoking, controlling blood pressure, adding a statin (ideally simvastatin 40 mg/day) and adding aspirin once their blood pressure is controlled. Blood glucose should also be controlled to control symptoms (probably using diet and lifestyle measures along with metformin) but the evidence indicates that the benefits of intensive control of blood glucose may be less than some patients and some healthcare professionals perceive.

You can find more information on the type 2 diabetes section of NPC.

Study details
Design: Randomised controlled trial
Patients: 160 patients with type 2 diabetes and persistent microalbuminuria. The mean treatment period was 7.8 years and patients were then followed observationally for a mean of 5.5 years
Intervention: Intensive therapy with the following targets:

  • glycated haemoglobin (HbA1c) level of less than 6.5%
  • a fasting serum total cholesterol level of less than 4.5 mmol per litre)
  • a fasting serum triglyceride level of less than 1.7 mmol per litre
  • a systolic blood pressure of less than 130 mm Hg
  • a diastolic blood pressure of less than 80 mm Hg.
  • Comparison: Conventional therapy following Danish guidelines
    Outcomes: The primary outcome was time to death from any cause. Secondary endpoints were death from CV causes and a composite of CV disease events e.g. death from CV causes, non-fatal stroke, non fatal myocardial infarction etc.
    Results: As above. Cardiovascular events were also reduced in the intensive therapy group compared with conventional therapy (HR 0.41, 95%CI 0.25 to 0.67; P<0.001). Few major side effects were reported.
    Sponsorship: Danish Health Research Council

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