Introduction

Introduction

The NICE clinical guideline on type 2 diabetes states that the management of type 2 diabetes is complex. It involves an individualised, multifactorial approach that addresses blood pressure, blood lipids and lifestyle issues, as well as blood glucose. As the MeReC Bulletin on type 2 diabetes discusses, controlling blood glucose needs a careful balance between the intensity of the treatment regimen and avoiding hypoglycaemia. The NICE clinical guideline on type 2 diabetes recommends that people should be involved in setting their individualised HbA1c target level, which may be above the general target of 48 mmol/mol (6.5%), and that pursuing highly intensive management to HbA1c levels below 48 mmol/mol (6.5%) should be avoided.

The natural hormone glucagon-like peptide-1 (GLP-1) acts by stimulating insulin secretion, suppressing glucagon secretion, inhibiting gastric emptying, and reducing appetite and food intake. In addition to lixisenatide, there are 2 other GLP-1 mimetics currently licensed and available in the UK: exenatide and liraglutide. All are administered by injection.

The NICE clinical guideline on type 2 diabetes, which is being updated, advises that consideration should be given to adding exenatide as third-line therapy in triple therapy in addition to metformin and a sulfonylurea when control of blood glucose remains or becomes inadequate (HbA1c 59 mmol/mol [7.5%] or greater, or other higher level agreed with the individual), and the person has:

  • a body mass index (BMI) of 35.0 kg/m2 or more 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 less than 35.0 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities.

The guideline also advises that exenatide should be continued only if the person has had a beneficial metabolic response (a reduction of at least 11 mmol/mol [1.0 percentage point] in HbA1c and a weight loss of at least 3% of initial body weight at 6 months).

The NICE technology appraisal on liraglutide for the treatment of type 2 diabetes mellitus recommends liraglutide 1.2 mg daily in triple therapy (in combination with metformin and a sulfonylurea, or metformin and a glitazone) as an option in the same clinical situations and with the same criteria for continuation as for exenatide in the NICE clinical guideline on type 2 diabetes.

The NICE technology appraisal on liraglutide recommends liraglutide 1.2 mg daily in dual therapy regimens (in combination with metformin or a sulfonylurea) as an option only if:

  • the person is intolerant of either metformin or a sulfonylurea, or treatment with metformin or a sulfonylurea is contraindicated, and

  • the person is intolerant of glitazones and dipeptidyl peptidase-4 (DPP-4) inhibitors, or treatment with glitazones and DPP-4 inhibitors is contraindicated.

It also recommends that treatment with liraglutide in a dual therapy regimen should only be continued if a beneficial metabolic response has been shown (defined as a reduction of at least 11 mmol/mol [1.0 percentage point] in HbA1c at 6 months).

The NICE technology appraisal on exenatide prolonged-release suspension for the treatment of type 2 diabetes recommends prolonged-release exenatide in triple therapy (in combination with metformin and a sulfonylurea, or metformin and a glitazone) as an option in the same clinical situations and with the same criteria for continuation as for exenatide in the NICE clinical guideline on type 2 diabetes. It also recommends prolonged-release exenatide in dual therapy (in combination with metformin or a sulfonylurea) as an option in the same clinical situations and with the same criteria for continuation as for liraglutide in dual therapy regimens in the NICE technology appraisal on liraglutide.

Lixisenatide in type 2 diabetes will be included in the update of the NICE clinical guideline for the management of type 2 diabetes. The publication date for this guideline is to be confirmed

See the MeReC Bulletin on type 2 diabetes, the type 2 diabetes key therapeutic topic and the NICE pathway on diabetes for more information. See also the Clinical Knowledge Summary on type 2 diabetes for a general overview of prescribing considerations.