NPC Archive Item: Another call to re-evaluate the emphasis given to tight control of blood glucose in type 2 diabetes

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27th April 2009

Many experienced clinicians are calling for a change in emphasis in care for patients with type 2 diabetes. Authors in a recent review express a similar view to a recent BMJ editorial, and say we should prioritise supporting well-being and healthy lifestyles, preventive care, and cardiovascular risk reduction ahead of tight glycaemic control. This is because randomised trial evidence does not strongly support the benefits of tight glycemic control in reducing the risk for diabetes complications and in some cases it may cause significant harm.

Health professionals and people with type 2 diabetes should prioritise lifestyle interventions (losing weight, healthy diet, stopping smoking if relevant), blood pressure control as well as taking a statin, aspirin if cardiovascular disease is present, and metformin. We should follow NICE guidance and agree individual targets for HbA1c, which could be above 6.5%, taking into account patient preferences and the balance of likely benefits and burden of treatment.

What is the background to this?
The authors reviewed the large randomised controlled trials which compared clinical outcomes among patients with type 2 diabetes who were randomly assigned to tight versus less tight glycaemic targets. They conclude that trial evidence does not strongly support tight glycaemic control as being more beneficial than harmful in reducing the risk for diabetes complications. Three important studies published recently (ACCORD, ADVANCE and VADT) support this conclusion. These studies and their implications have been discussed in several previous NPCi blogs:

The authors of this article note that there is conflicting evidence about the possible value of tight control in people with earlier and milder disease. They argue that tight control in such people needs to be tested in long term controlled trials, since assuming its value and imposing it on patients exposes them to extra treatment burden and expense, harms from risk of hypoglycaemia and uncertain benefit. In addition, some drugs may have specific harmful effects: for example, glitazones increase the risk of heart failure, double the risk of bone fracture in women and there is some evidence to suggest that rosiglitazone in particular may be associated with an increased risk of myocardial infarction.

The authors also note that focusing on composite endpoints may overstate benefits. For example, in the ADVANCE trial, tight glucose control led to a 10% relative reduction in the risk of the headline composite of major macrovascular and microvascular events. However, there was no statistically significant benefit on all-cause mortality, or major vascular events, or cardiovascular mortality, or retinopathy. Most of the observed benefit on the overall composite came from an effect on new or worsening nephropathy. This was itself a composite, which combined patient-oriented outcomes (POOs) — the need for renal-replacement therapy or death from renal causes —  with a  disease-oriented outcome (DOO), macroalbuminuria. The individual POOs in this composite showed no statistically significant difference: the overall benefit was driven by a 1.2% absolute risk reduction in albuminuria. Although composite outcomes are justifiable and indeed may be necessary to enable a study to have sufficient power, it is important that their components are of similar clinical importance.

What place blood glucose targets?
The authors suggest an approach to blood glucose control which is entirely in keeping with NICE guidance. They suggest that an HbA1c target of 7% to 7.5% is a reasonable aspiration for many patients and may be feasible to attain without increasing the risk of harm and the need for multiple hypoglycaemic agents. However, importantly, this will not apply to all people with type 2 diabetes. Blood glucose targets should be agreed with the patient and can be adjusted — up or down — according to the burden of treatment, side effects, and the patient’s context, values and preferences. For most people, keeping blood glucose levels below about 10mmol/L will prevent symptoms associated with hyperglycaemia. This is equivalent to an HbA1c of about 9%, and the authors suggest that it may be more desirable for policy makers to use HbA1c >9% as an indicator of possible inadequate care, rather than setting targets which may encourage less patient-centred care.

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