The British Medical Journal has published the results of a meta-analysis that aimed to assess the effect of intensive blood glucose lowering on cardiovascular outcomes and microvascular events in patients with type 2 diabetes.
The analysis included 13 studies involving 34,533 participants (18,315 in the intensive treatment group and 16,218 in the standard treatment group). The primary outcomes for the study were all cause mortality and cardiovascular death with secondary outcomes of severe hypoglycaemia, macrovascular and microvascular events. The studies all involved patients over the age of 18 years (mean age of 62 years) and with a diagnosis of type 2 diabetes. The mean follow up for the studies was 5 years.
There was no difference noted in the primary outcomes. In the secondary outcomes, intensive glucose lowering was associated with a reduced risk of non-fatal myocardial infarction and new onset microalbuminuria but an increased risk of severe hypoglycaemia.
The results of this analysis indicate that intensively lowering blood glucose in 600 patients for 5 years would:
- Prevent 4 or 5 non-fatal myocardial infarctions
- Present 4 to 20 cases of new onset microalbuminuria
- Cause 12 to 40 cases of severe hypoglycaemia
The authors conclude that, "the overall results of this meta-analysis show limited benefits of intensive glucose lowering treatment". They note that the risk:benefit ratio of intensive glucose lowering remains uncertain and that more randomised controlled trials are needed.
This study adds yet more weight to using an holistic approach to treat type 2 diabetes with due consideration of preventing macrovascular and microvascular complications. Lifestyle interventions, blood pressure and lipid management should be prioritised ahead of intensive glucose management.
Action: Clinicians should be aware of this analysis. Intensive glucose lowering should only be a consideration once all other interventions are effectively implemented.
The Joint Committee on Vaccination and Immunisation (JCVI) has issued revised advice (PDF) regarding the routine pneumococcal vaccination programme for adults aged 65 years and older using pneumococcal polysaccharide vaccine (PPV).
In March this year, advice was issued that the programme should be discontinued because there have been no discernible reduction in the rate of invasive pneumococcal disease since the introduction of the vaccine. The DH sought the views of professional and patient groups and the vaccine manufacturers before making a final decision. Following a review of all the submissions and a new analysis the JCVI have concluded that, "whilst uncertainty remains about the effectiveness of PPV, there is better evidence from the UK experience of the vaccine suggesting that PPV provides some moderate short-term protection to those aged 65 years and older, although protection may be less and wane faster in older age groups and for some clinical risk groups".
The JCVI have therefore recommended continuing the current programme with routine use recommended in individuals aged 65 years and older. It is also suggested that the efficacy of the programme is reviewed again in 2 years time.
This revised advice is the subject of a Department of Health (DH) letter (PDF) that states that the new analysis indicates that the programme remains cost effective despite the limited effectiveness of the vaccine.
Action: Clinicians should be aware of this review and final decision. Clinicians should continue to implement the advice in the Green Book.
The European Medicines Agency (EMA) has recommended (PDF) several new contra-indications and warnings for pioglitazone (Actos®) to minimise the impact of a small increased risk of bladder cancer.
The review concluded that "these medicines remain a valid treatment option for certain patients with type 2 diabetes" but that "the small increased risk could be reduced by appropriate patient selection and exclusion".
Clinicians are advised to not use pioglitazone in:
- Patients with bladder cancer
- Patients with a history of bladder cancer
- Patients with uninvestigated macroscopic haematuria
Risk factors for bladder cancer should be assessed before starting treatment, especially in older patients and treatment should be regularly reviewed and only continued when treatment continues to provide a benefit.
The relative risk of bladder cancer from three recent observational studies ranges from 1.12 to 1.33. A meta-analysis of randomised controlled trials indicated an absolute risk increase of 0.08% (7 cases in 10,212 patients or 0.07% risk in the placebo group versus 19 cases in 12,506 patients or 0.15% in the treatment group).
The EMA has also requested that a pan-European epidemiological study is conducted to provide more robust information about the risk.
Action: Clinicians should be aware of this review and the additional warnings and contra-indications for pioglitazone. The figures quoted in the review may be helpful when explaining the risks to patients.
UPDATE: A summary is now available from the Medicines and Healthcare products Regulatory Agency (MHRA).
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