The Journal of the American Medical Association has published the results of a meta-analysis that aimed to assess the comparative efficacy, risk of weight gain and risk of hypoglycaemia associated with non-insulin hypoglycaemic agents when used in addition to metformin.
The study analysed data from 27 randomised controlled studies involving 11,198 participants. Comparisons were made between sulphonylureas, glinides (nateglinide, rapeglinide), glitazones (pioglitazone, rosiglitazone), alpha-glucosidase inhibitors (acarbose), GLP-1 analogs (exenatide, liraglutide) and DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin). The studies varied in duration from 12-52 weeks.
All of the treatments were associated with similar reductions in HbA1c but there were differences in the risk of weight gain and hypoglycaemia. Sulphonylureas, glitazones and glinides were all associated with weight gain. Sulphonylureas and glinides were associated with hypoglycaemia.
The authors conclude that, "these factors and other considerations should be taken into account when selecting a second-line treatment to add to stable, maximum metformin".
Action: These results are not surprising and the recommendations are in keeping with the current NICE Guideline for diabetes. Clinicians should consider the relative benefits of the second-line agents with due regard for patient factors and acquisition cost.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on new medicines.
Metformin powder for oral solution (Glucophage®) has been accepted for restricted use in the treatment of type 2 diabetes mellitus in patients who are unable to swallow the solid dosage formulation.
Tacrolimus 0.03% ointment (Protopic®) has been accepted for restricted use as a maintenance treatment of moderate to severe atopic dermatitis for the prevention of flares and the prolongation of flare-free intervals in children experiencing a high frequency of disease exacerbations provided it is initiated by a dermatologists in secondary care.
Tacrolimus 0.1% ointment (Protopic®) has been accepted for restricted use for the maintenance treatment of moderate to severe atopic dermatitis for the prevention of flares and the prolongation of flare-free intervals in adult patients experiencing a high frequency of disease exacerbations provided it is initiated by a dermatologists in secondary care.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The National Institute for Health and Clinical Excellence has issued an update to the Lipid Modification Guideline relating to recommendations on methods of cardiovascular risk estimation.
The original guideline recommended using a Framingham based risk estimation tool however recent developments in the evidence comparing different risk estimation tools has resulted in no single tool having a clear advantage.
As a result clinicians can now consider using QRISK or Framingham-based tools. In Scotland, clinicians are already advised to use ASSIGN when estimating cardiovascular risk.
Action: Clinicians should be aware of this update and consider which risk prediction tool should be used in practice. Whichever tool is used, clinicians should be aware of any limitations and corrections required in use.
The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for April 2010 (PDF).
This issue contains drug safety advice regarding the risk of venous thromboembolism (VTE) with Yasmin® covers the recently updated EMA regarding the interaction between clopidogrel and omeprazole or esomeprazole.
This update notes that the risk of VTE expected with Yasmin® was expected to be similar to that seen with levonorgestrel containing, or second generation, contraceptive pills. This was confirmed in two prospective cohort studies. However, two more recent studies, one a Danish cohort study and one a Dutch case-control study, have indicated that the risk may be higher than previously thought. The relative risk of VTE was quoted as 1.64 (95% CI 1.27-2.10) and 1.7 (95% CI 0.7-3.9) respectively which would place the risk between second and third generation combined oral contraceptives but still below the risk associated with pregnancy.
Some methodological flaws are present in both of these more recent studies and as such no firm conclusions can be made at this time. Clinicians are advised to discuss this new information with patients before prescribing or at the next routine review. Patients are advised to continue taking this medication but seek advice if they are worried.
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.