The manufacturer of rosiglitazone (Avandia® and Avandamet®) has written to healthcare professionals to highlight the increased risk of fractures identified in the ADOPT Study.
The ADOPT Study compared monotherapy with metformin, glibenclamide and rosiglitazone in achieving glycaemic control in over 4,000 patients with type 2 diabetes. Significantly more fractures of bones in the hands, feet and upper arm were seen in women taking rosiglitazone compared to the other two trial drugs.
Some interesting points to note are:
- The increase in risk was not observed in male patients
- The fractures were not typical of fragility fractures (e.g. spine and hip)
- Patients taking rosiglitazone were more likely to have gained weight compared to metformin
- Patients taking rosiglitazone were more likely to be prescribed statins and loop diuretics
However, an early analysis of an on-going study has reported observations that are consistent with these results. It is therefore recommended that the risk of fracture is considered, especially in female patients, who are being prescribed or being considered for initiation on treatment with rosiglitazone.
Action: Metformin remains the first line hypoglycaemic in type 2 diabetes. It is unknown if this increased fracture risk applies only to rosiglitazone or to all glitazones and therefore fracture risk should be considered before starting treatment with any glitazone and during medication reviews for patients already on treatment.
A new drug has been launched for the treatment of type 2 diabetes. Exenatide (Byetta®) is a subcutaneous injection indicated for use in combination with metformin and/or sulphonylureas in patients not achieving adequate glycaemic control.
A dose of 5 micrograms is recommended for the first month to improve tolerability before moving onto the 10 microgram dose. The injection is given twice daily up to a maximum of 60 minutes before eating.
Exenatide is not recommended for use in pregnancy or breast feeding. It should be used cautiously in patients with moderate renal impairment. Patients with severe renal impairment or end stage renal disease should not take this drug. Safety and efficacy have not been evaluated in patients aged below 18 years of above 75 years.
Hypoglycaemia, nausea, vomiting and diarrhoea are listed as very common side effects (occurring in more than 10% of patients). Common side effects (occurring in 1-10% of patients) include headache, dizziness, dyspepsia, abdominal pains, gastro-oesophageal reflux disease and abdominal distension.
Further prescribing information is contained in the Summary of Product Characteristics.
Action: A place in therapy for exenatide is yet to be established but it would appear to be very limited. In patients uncontrolled on one oral agent there is the option of adding another oral agent from the range available. When all oral agents have been exhausted this product does not appear to offer any advantages over insulin.
The Scottish Medicines Consortium (SMC) has issued new guidance on several medicines including rejecting Glyceryl Trinitrate 0.4% Ointment (Rectogesic)® for use on the NHS in Scotland for a third time and restricting the place of pioglitazone (Actos®) in triple therapy.
As previously discussed, Glyceryl Trinitrate 0.4% Ointment has been rejected after failing to make a robust economic case supporting its use on the NHS. The SMC have upheld this previous guidance after a resubmission. First line treatment of anal fissures remains focused upon lifestyle advice about diet and bowel habit.
The SMC has also reviewed the place of pioglitazone in triple oral therapy for type 2 diabetes where glycaemic control is not optimal despite dual therapy treatment. It is advised that the triple therapy approach is reserved for patients unable or unwilling to take insulin.
Action: Clinicians should be aware of this latest advice and ensure that the recommendations are adopted into current practice.
The Medicines and Healthcare products Regulatory Agency has opened a public consultation on the proposal to restrict access to the availability of pseudoephedrine and ephedrine.
This consultation is in response to the Annual Report of the International Narcotics Control Board that identified that these medicines are used in the illegal manufacture of methylamphetamine, a Class A drug more commonly known as crystal meth.
Action: All healthcare professionals should be aware of the consultation and of the potential to illegally use pseudoephedrine and ephedrine in the manufacture of a Class A drug. Supplies of both drugs should be restricted to ensure inappropriate use is kept to a minimum.
The open-access journal PLoS Medicine has published an essay discussing the flaws in using bone mineral density or "bone quality" as predictors for fragility fractures.
The article raises three flaws with the concept of bone quality. Firstly, there is only a poor link between bone mineral density (BMD) and fragility fractures with less than half of fragility fractures occurring in people with the World Health Organization's definition of osteoporosis. Secondly, the concept of BMD is too imprecise to define bone quality as it provides an overall picture of bone density because there is no accounting for structural changes such as porosity and trabecular thickness. Finally, the overall concept of bone quality is criticised as it incorporates many other indices for bone fragility (non-BMD) without established a unit of measurement or a definition of "good" and "bad" scores.
The National Institute of Health and Clinical Excellence (NICE) are expected to publish guidelines on the primary prevention and secondary prevention of osteoporotic fragility fractures in August 2007.
Action: Clinicians should continue to implement the existing NICE guideline on secondary prevention of osteoporotic fractures. It would also be prudent to avoid initiating treatments based solely upon BMD scores until NICE publish the new guidelines in August.