11 November 2010
NICE has issued guidance on the use of liraglutide▼ for the treatment of type 2 diabetes. Liraglutide 1.2mg is a dual therapy option only in very limited circumstances in people who are unable to take metformin or a sulphonylurea AND are unable to take a glitazone AND are unable to take a gliptin. Liraglutide 1.2mg daily is a triple therapy option for people whose HbA1c is ≥7.5% (59mmol/mol) (or other higher level agreed with the individual) and whose body weight meets specific criteria (see below). Treatment with liraglutide 1.2mg daily in a triple therapy regimen should only be continued if HbA1c is reduced by at least 1.0% (11mmol/mol) and body weight is reduced by at least 3% at six months. NICE does not recommend liraglutide at a dose of 1.8mg daily.
Healthcare professionals involved in the care and treatment of people with type 2 diabetes should familiarise themselves with this technology appraisal, and base their management on this, alongside the diabetes guideline from NICE. The NICE guideline on type 2 diabetes recommends metformin as the usual first-line hypoglycaemic drug; dual therapy with metformin and a sulphonylurea as the normal second-line therapy; and triple therapy with insulin added to metformin and a sulphonylurea as the usual third-line option.
The role of newer hypoglycaemic agents in the management of type 2 diabetes, particularly in the pursuit of ever tighter blood glucose control, is controversial, as we have previously blogged (MeReC Rapid Review No. 1017, MeReC Rapid Review No. 435, MeReC Rapid Review No. 336). We should bear in mind that, as yet, there is no robust evidence that liraglutide▼ or exenatide▼ reduce the likelihood of patient-oriented outcomes such as cardiovascular disease or other diabetic complications. In addition, these drugs are injectable preparations and their long-term safety data are limited.
What are the conclusions from NICE regarding dual therapy?
Taking into account the uncertainty around the data presented, NICE concluded that liraglutide 1.2mg could not be recommended over the other options available for dual therapy regimens (which would include metformin, sulphonylureas, pioglitazone or gliptins). They point out that a large number of people require dual therapy regimens for diabetes so there needs to be a high degree of certainty in introducing new treatments at this stage. NICE also notes the lack of long-term safety data for liraglutide and that it is an injected agent whereas current dual therapy options are oral therapies. Nevertheless, NICE discussed whether liraglutide should be an option for those people unable to take multiple oral therapy options and whose only current alternative treatment is early initiation of insulin. Following these discussions, they concluded that liraglutide may be considered in a dual therapy regimen as outlined below. However, this would seem to be in very limited circumstances in people who are unable to take metformin or a sulphonylurea AND are unable to take a glitazone AND are unable to take a gliptin.
Liraglutide 1.2mg daily in dual therapy regimens (in combination with metformin or a sulphonylurea) is recommended as an option for the treatment of people with type 2 diabetes, only if:
- the person is intolerant of either metformin or a sulphonylurea, or treatment with metformin or a sulphonylurea is contraindicated, and
- the person is intolerant of glitazones (also called thiazolidinediones i.e. pioglitazone) and gliptins (also called DPP-4 inhibitors i.e. sitagliptin▼, vildagliptin▼ or saxagliptin▼), or treatment with glitazones and gliptins is contraindicated.
Treatment with liraglutide 1.2mg daily in a dual therapy regimen should only be continued if a beneficial metabolic response has been shown (defined as a reduction of at least 1% [11mmol/mol] in HbA1c at six months).
What about triple therapy?
NICE did not consider that the evidence provided was robust enough to allow it to recommend liraglutide as a cost-effective alternative to either glitazones or gliptins as a triple therapy regimen. However, NICE comment that liraglutide may have some advantages over exenatide and insulin, in particular its effect on weight relative to insulin, and also because it is a once-daily injection compared with twice daily for exenatide.
Liraglutide 1.2mg daily in triple therapy regimens (in combination with metformin and a sulphonylurea, or metformin and a glitazone) is recommended as an option for the treatment of people with type 2 diabetes, only if used as described for exenatide in NICE guidance on type 2 diabetes i.e. when control of blood glucose remains or becomes inadequate (HbA1c ≥7.5% [59mmol/mol] or other higher level agreed with the individual), and the person has:
- a body mass index (BMI) ≥35 kg/m2 in those of European descent (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or
- a BMI <35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities.
As with exenatide, treatment with liraglutide in a triple therapy regimen should only be continued if a beneficial metabolic response has been shown (defined as a reduction of at least 1% [11mmol/mol] in HbA1c and a weight loss of at least 3% of initial body weight at six months).
What about the higher dose?
NICE concluded that liraglutide 1.8mg would not be a cost-effective use of NHS resources, and therefore should not be recommended for the treatment of type 2 diabetes.
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