8th June 2009
NICE clinical guideline 87 partially updates recommendations for the management of type 2 diabetes, with specific new recommendations about blood glucose control with sitagliptin▼, vildagliptin▼, pioglitazone▼, rosiglitazone▼, exenatide▼ and insulin therapy. This updates the previous clinical guideline 66 published in May 2008.
Healthcare professionals involved in the care and treatment of people with type 2 diabetes should familiarise themselves with this updated guideline, and base their management on this.
What does the new guideline cover?
- This is a partial update of the previous clinical guideline 66 (published in May 2008), to address the role of newer drugs for management of blood glucose. Most of guideline 66 is unchanged, i.e.
- the monitoring of glucose, lipid and blood pressure levels
- diabetes education programmes
- dietary advice
- the use of medications to control blood glucose, prevent vascular disease, reduce blood pressure, and improve lipid levels (new guidance has been added but what was previously in CG 66 still remains)
- the detection and ongoing management (with referral to a specialist if necessary) of eye disease, kidney disease, nerve damage and nerve pain, and depression.
What has changed?
Only the section on the use of medications to control blood glucose has new recommendations. These relate to the use of DPP-4 inhibitors (sitagliptin▼ and vildagliptin▼), glitazones (pioglitazone▼ and rosiglitazone), the GLP-1 mimetic (exenatide▼) and insulin therapy. These updated recommendations are based on the new short clinical guideline 87, ‘Type 2 diabetes newer agents for blood glucose control in type 2 diabetes’, which has been published separately and contains more detail. There are no recommendations on liraglutide as this has not yet received marketing authorisation.
The new recommendations use the same level of HbA1c for the addition of extra glucose-lowering drugs as defined in the earlier guideline. That is a value of 6.5% (or other higher level agreed with the individual) for people on one glucose-lowering drug and 7.5% (or other higher level agreed with the individual) for people on two or more oral glucose-lowering drugs or insulin.
What are the new recommendations for blood glucose control?
The quick reference guide gives a helpful updated algorithm for blood-glucose lowering therapy.
In summary, metformin is still the first-choice hypoglycaemic drug, with a sulphonylurea as an option if the patient is not overweight, if a rapid therapeutic response is required, or if metformin is contraindicated or not tolerated.
If blood glucose control is inadequate on monotherapy (HbA1c ≥6.5% or other higher level agreed with the individual), dual therapy with metformin and a sulphonylurea remains the normal second-line therapy. Rapid-acting insulin secretagogues, such as repaglinide and nateglinide, are still only recommended for people with erratic lifestyles. Other alternatives may be considered in particular patient circumstances (see below).
The normal third-line option, if HbA1c levels remain at ≥7.5% (or other higher level agreed with the individual) is to initiate insulin therapy in addition to metformin and a sulphonylurea (or whatever dual therapy is being taken, see below, within licensed indications). The new guidance states that for a person on dual therapy who is markedly hyperglycaemic, insulin therapy should be considered in preference to adding other drugs to control blood glucose unless there is strong justification not to. Intermediate acting human isophane insulin (human NPH insulin) remains the preferred basal insulin, taken at bedtime or twice-daily according to need. Alternatives may be considered in particular patient circumstances (see below).
Combining pioglitazone▼* with insulin therapy can be considered for a person who has previously had a marked glucose-lowering response to glitazone therapy, or who is on high-dose insulin therapy and whose blood glucose is inadequately controlled.
What recommended alternatives are there to metformin and sulfonylurea dual therapy?
As in the previous guidance, glitazones (and now also sitagliptin▼or vildagliptin▼) can be considered for dual therapy with either metformin or a sulphonylurea when either of these latter drugs is contraindicated, not tolerated or (in the case of sulphonylureas) there is a significant risk of hypoglycaemia. NICE reiterates safety advice about glitazones i.e. that they should not be used in people with heart failure or at high risk of fracture (see previous blog) and that up to date advice from the EMEA and MHRA should be taken into account before prescribing (see the December 2007 Drug Safety Update)
There is also a new recommendation that pioglitazone▼, rosiglitazone, sitagliptin▼ or vildagliptin▼ should be continued only if the person has a beneficial metabolic response to therapy (a reduction of at least 0.5% in HbA1c in 6 months).
When choosing between glitazone (pioglitazone▼or rosiglitazone) or DPP-4 inhibitor (sitagliptin▼or vildagliptin▼) therapy, NICE state that a DPP-4 inhibitor may be preferred if:
- further weight gain would cause or exacerbate significant problems associated with high body weight, or
- a glitazone is contraindicated, or
- the person has previously had a poor response to, or did not tolerate, a glitazone.
Likewise, a glitazone may be preferred if:
- the person has marked insulin insensitivity, or
- a DPP-4 inhibitor is contraindicated, or
- the person has previously had a poor response to, or did not tolerate, a DPP-4 inhibitor.
When either a glitazone or a DPP-4 inhibitor may be suitable, NICE recommends that the choice of treatment should be based on patient preference.
What recommended alternatives are there to insulin therapy?
Sitagliptin▼** or a glitazone can be considered for triple therapy with metformin and a sulphonylurea instead of insulin if insulin is unacceptable or inappropriate (because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity).
Exenatide▼can now be considered for triple therapy in addition to metformin and a sulphonylurea in people whose HbA1c is ≥7.5% (or other higher level agreed with the individual), if either:
- their BMI is >35 kg/m2 in people of European descent (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or
- their BMI is < 35.0 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities.
However, exenatide▼ should be continued only if the person has a beneficial metabolic response (a reduction of at least 1.0% in HbA1c and a weight loss of at least 3% of initial body weight at 6 months).
*only pioglitazone▼not rosiglitazone is licensed for use with insulin
**only sitagliptin▼, not vildagliptin▼ is licensed for use with metformin and a sulphonylurea
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