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Centre for Clinical Practice at NICE (UK). Type 2 Diabetes: Newer Agents for Blood Glucose Control in Type 2 Diabetes. London: National Institute for Health and Clinical Excellence (UK); 2009 May. (NICE Clinical Guidelines, No. 87.)

Cover of Type 2 Diabetes

Type 2 Diabetes: Newer Agents for Blood Glucose Control in Type 2 Diabetes.

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1Summary

1.1. List of all recommendations1

DPP-4 inhibitors (sitagliptin, vildagliptin)

1.1.1.

Consider adding a DPP-4 inhibitor (sitagliptin, vildagliptin) instead of a sulfonylurea as second-line therapy to first-line metformin when control of blood glucose remains or becomes inadequate (HbA1c ≥ 6.5%, or other higher level agreed with the individual) if:

  • the person is at significant risk of hypoglycaemia or its consequences (for example, older people and people in certain jobs for example, those working at heights or with heavy machinery] or people in certain social circumstances [for example, those living alone]), or
  • the person does not tolerate a sulfonylurea or a sulfonylurea is contraindicated.
1.1.2.

Consider adding a DPP-4 inhibitor (sitagliptin, vildagliptin) as second-line therapy to first-line sulfonylurea monotherapy when control of blood glucose remains or becomes inadequate (HbA1c ≥ 6.5%, or other higher level agreed with the individual) if:

  • the person does not tolerate metformin, or metformin is contraindicated.
1.1.3.

Consider adding sitagliptin2 as third-line therapy to first-line metformin and a second-line sulfonylurea when control of blood glucose remains or becomes inadequate (HbA1c ≥ 7.5% or other higher level agreed with the individual) and insulin is unacceptable or inappropriate3.

1.1.4.

Only continue DPP-4 inhibitor therapy (sitagliptin, vildagliptin) if the person has had a beneficial metabolic response (a reduction of at least 0.5 percentage points in HbA1c in 6 months).

1.1.5.

Discuss the potential benefits and risks of treatment with a DPP-4 inhibitor (sitagliptin, vildagliptin) with the person to enable them to make an informed decision.

A DPP-4 inhibitor (sitagliptin, vildagliptin) may be preferable to a thiazolidinedione (pioglitazone, rosiglitazone) if:

  • further weight gain would cause or exacerbate significant problems associated with a high body weight, or
  • a thiazolidinedione (pioglitazone, rosiglitazone) is contraindicated, or
  • the person has previously had a poor response to, or did not tolerate, a thiazolidinedione (pioglitazone, rosiglitazone).

There may be some people for whom either a DPP-4 inhibitor (sitagliptin, vildagliptin) or a thiazolidinedione (pioglitazone, rosiglitazone) may be suitable and, in this case, the choice of treatment should be based on patient preference.

Thiazolidinediones (pioglitazone, rosiglitazone)

The marketing authorisation for rosiglitazone has been suspended. See September 2010 Update for details.

The Medicines and Healthcare products Regulatory Agency has issued new advice on risk of bladder cancer with the anti-diabetic drug pioglitazone. Please refer to the advice when prescribing pioglitazone.

1.1.6.

Consider adding a thiazolidinedione (pioglitazone, rosiglitazone) instead of a sulfonylurea as second-line therapy to first-line metformin when control of blood glucose remains or becomes inadequate (HbA1c ≥ 6.5%, or other higher level agreed with the individual) if:

  • the person is at significant risk of hypoglycaemia or its consequences (for example, older people and people in certain jobs [for example, those working at heights or with heavy machinery] or people in certain social circumstances [for example, those living alone]), or
  • a person does not tolerate a sulfonylurea or a sulfonylurea is contraindicated.
1.1.7.

Consider adding a thiazolidinedione (pioglitazone, rosiglitazone) as second-line therapy to first-line sulfonylurea monotherapy when control of blood glucose remains or becomes inadequate (HbA1c ≥ 6.5%, or other higher level agreed with the individual) if:

  • the person does not tolerate metformin or metformin is contraindicated.
1.1.8.

Consider adding a thiazolidinedione (pioglitazone, rosiglitazone) as third-line therapy to first-line metformin and a second-line sulfonylurea when control of blood glucose remains or becomes inadequate (HbA1c ≥ 7.5%, or other higher level agreed with the individual) and insulin is unacceptable or inappropriate4.

1.1.9.

Do not commence or continue a thiazolidinedione (pioglitazone, rosiglitazone) in people who have heart failure, or who are at higher risk of fracture.

1.1.10.

When selecting a thiazolidinedione (pioglitazone, rosiglitazone), take into account up-to-date advice from the relevant regulatory bodies (the European Medicines Agency and the Medicines and Healthcare products Regulatory Agency), cost, safety and prescribing issues (see 1.1.13).

1.1.11.

Only continue thiazolidinedione therapy (pioglitazone, rosiglitazone) if the person has had a beneficial metabolic response (a reduction of at least 0.5 percentage points in HbA1c in 6 months).

1.1.12.

Consider combining pioglitazone with insulin therapy5 for a person:

  • who has previously had a marked glucose-lowering response to thiazolidinedione therapy (pioglitazone, rosiglitazone), or
  • who is on high-dose insulin therapy and whose blood glucose is inadequately controlled.
1.1.13.

Discuss the potential benefits and risks of treatment with a thiazolidinedione (pioglitazone, rosiglitazone) with the person to enable them to make an informed decision.

A thiazolidinedione (pioglitazone, rosiglitazone) may be preferable to a DPP-4 inhibitor (sitagliptin, vildagliptin) if:

  • the person has marked insulin insensitivity, or
  • a DPP-4 inhibitor (sitagliptin, vildagliptin) is contraindicated, or
  • the person has previously had a poor response to, or did not tolerate, a DPP-4 inhibitor (sitagliptin, vildagliptin).

There may be some people for whom either a thiazolidinedione (pioglitazone, rosiglitazone) or a DPP-4 inhibitor (sitagliptin, vildagliptin) may be suitable and, in this case, the choice of treatment should be based on patient preference.

GLP-1 mimetic (exenatide)

1.1.14.

Consider adding a GLP-1 mimetic (exenatide) as third-line therapy to first-line metformin and a second-line sulfonylurea when control of blood glucose remains or becomes inadequate (HbA1c ≥ 7.5%, or other higher level agreed with the individual), and the person has:

  • a body mass index (BMI) ≥ 35.0 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 < 35.0 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities.
1.1.15.

Only continue GLP-1 mimetic (exenatide) therapy if the person has had a beneficial metabolic response (a reduction of at least 1.0 percentage point in HbA1c and a weight loss of at least 3% of initial body weight at 6 months).

1.1.16.

Discuss the potential benefits and risks of treatment with a GLP-1 mimetic (exenatide) with the person to enable them to make an informed decision.

Insulin therapy

1.1.17.

Discuss the benefits and risks of insulin therapy when control of blood glucose remains or becomes inadequate (HbA1c ≥ 7.5% or other higher level agreed with the individual) with other measures. Start insulin therapy if the person agrees.

1.1.18.

For a person on dual therapy who is markedly hyperglycaemic, consider starting insulin therapy in preference to adding other drugs to control blood glucose unless there is strong justification6 not to.

1.1.19.

When starting insulin therapy, use a structured programme employing active insulin dose titration that encompasses:

  • structured education
  • continuing telephone support
  • frequent self-monitoring
  • dose titration to target
  • dietary understanding
  • management of hypoglycaemia
  • management of acute changes in plasma glucose control
  • support from an appropriately trained and experienced healthcare professional.7
1.1.20.

Initiate insulin therapy from a choice of a number of insulin types and regimens.

  • Begin with human NPH insulin injected at bed-time or twice daily according to need.
  • Consider, as an alternative, using a long-acting insulin analogue (insulin detemir, insulin glargine) if:

    the person needs assistance from a carer or healthcare professional to inject insulin, and use of a long-acting insulin analogue (insulin detemir, insulin glargine) would reduce the frequency of injections from twice to once daily, or

    the person’s lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes, or

    the person would otherwise need twice-daily NPH insulin injections in combination with oral glucose-lowering drugs, or

    the person cannot use the device to inject NPH insulin.

  • Consider twice-daily pre-mixed (biphasic) human insulin (particularly if HbA1c ≥ 9.0%). A once-daily regimen may be an option.
  • Consider pre-mixed preparations that include short-acting insulin analogues, rather than pre-mixed preparations that include short-acting human insulin preparations, if:

    a person prefers injecting insulin immediately before a meal, or

    hypoglycaemia is a problem, or

    blood glucose levels rise markedly after meals.

1.1.21.

Consider switching to a long-acting insulin analogue (insulin detemir, insulin glargine) from NPH insulin in people:

  • who do not reach their target HbA1c because of significant hypoglycaemia, or
  • who experience significant hypoglycaemia on NPH insulin irrespective of the level of HbA1c reached, or
  • who cannot use the device needed to inject NPH insulin8 but who could administer their own insulin safely and accurately if a switch to a long-acting insulin analogue were made, or
  • who need help from a carer or healthcare professional to administer insulin injections and for whom switching to a long-acting insulin analogue would reduce the number of daily injections.
1.1.22.

Monitor a person on a basal insulin regimen (NPH insulin or a long-acting insulin analogue [insulin detemir, insulin glargine]) for the need for short-acting insulin before meals (or a pre-mixed insulin preparation).

1.1.23.

Monitor a person who is using pre-mixed insulin once or twice daily for the need for a further injection of short-acting insulin before meals or for a change to a regimen of mealtime plus basal insulin, based on NPH insulin or long-acting insulin analogues (insulin detemir, insulin glargine), if blood glucose control remains inadequate.

1.2. Care pathway

Flowchart Icon

Blood-glucose-lowering theraphy (PDF, 468K)

1.3. Overview

1.3.1. Use of newer agents for blood glucose control

Type 2 diabetes is a chronic metabolic disorder caused by relative insensitivity to insulin combined with insufficient insulin secretion. It is characterised by high levels of blood glucose (hyperglycaemia). If prolonged, hyperglycaemia can cause microvascular and macrovascular damage. Improving blood glucose levels, blood pressure and lipid levels delays or prevents the complications of diabetes. Current practice aims to achieve a glycated haemoglobin (HbA1c) level of 6.5%, or 7.5% for those at risk of severe hypoglycaemia, although healthcare professionals appreciate that these targets will not be achieved by everyone.

The prevalence of diagnosed diabetes approximates 3.7% in England and 4.2% in Wales. This equates to more than 2 million people, of whom more than 85% have type 2 diabetes. Diabetes is estimated to account for at least 5% of healthcare expenditure in the UK, and up to 10% of hospital budgets. Type 2 diabetes usually occurs in people older than 40 years; however, it can occur earlier, particularly in people of South Asian or African – Caribbean origin.

Although lifestyle interventions (diet and physical activity) are the first-line treatments for the management of type 2 diabetes, most people subsequently need sequential addition of oral glucose-lowering drugs. Metformin is widely used as first-line oral therapy, with the sulfonylureas added as second-line therapy if glycaemic control remains poor or deteriorates. Other oral drugs for lowering blood glucose include alpha-glucosidase inhibitors, thiazolidinediones and meglitinides. Because type 2 diabetes is progressive, with secretion of insulin decreasing over time, most people with type 2 diabetes eventually need insulin. Healthcare professionals can prescribe a variety of formulations of insulin, including long- or short-acting formulations, or a pre-mixed (biphasic) combination of short- and long-acting insulins.

In recent years new agents have been developed for blood glucose control.

These include:

In addition, there have been recent safety concerns on the use of thiazolidinediones (pioglitazone and rosiglitazone) for blood glucose control in type 2 diabetes.

This short clinical guideline aims to improve the care of adults with type 2 diabetes by making evidence-based recommendations on the place of these newer drugs for blood glucose control in the care pathway.

1.3.2. The NICE short clinical guideline programme

‘Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes’ (NICE short clinical guideline 87) is a NICE short clinical guideline. For a full explanation of the process, see www.nice.org.uk/guidelinesmanual.

1.3.3. Using this guideline

This document is for healthcare professionals involved in the management of people with type 2 diabetes. The target population is adults with type 2 diabetes. This guidance does not apply to pregnant women with diabetes.

This is the full version of the guideline. It is available from www.nice.org.uk/CG87. Printed summary versions of this guideline are available: ‘Understanding NICE guidance’ (a version for patients and carers) and a quick reference guide (for healthcare professionals). These are also available from www.nice.org.uk/CG87

1.3.4. Using recommendations and supporting evidence

The Guideline Development Group (GDG) reviewed the evidence (see section 4 and appendices 6.2 and 6.3). For each clinical question, the GDG was presented with a summary of the clinical and economic evidence, based on the studies reviewed and appraised. From this information the GDG derived the guideline recommendations. The link between the evidence and the view of the GDG in making each recommendation is made explicit in section 2.7 ‘Interpreting the evidence to make recommendations’.

Oral drugs are listed first.

At the time of publication, sitagliptin was the only DDP-4 inhibitor with UK marketing authorisation for use in this combination.

Because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity.

Because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity.

At the time of publication pioglitazone was the only thiazolidinedione with UK marketing authorisation for use with insulin.

Because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity.

This recommendation is from NICE clinical guideline 66.

See NICE clinical guideline 87.

Footnotes

1

Oral drugs are listed first.

2

At the time of publication, sitagliptin was the only DDP-4 inhibitor with UK marketing authorisation for use in this combination.

3

Because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity.

4

Because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity.

5

At the time of publication pioglitazone was the only thiazolidinedione with UK marketing authorisation for use with insulin.

6

Because of employment, social or recreational issues related to putative hypoglycaemia, injection anxieties, other personal issues or obesity.

7

This recommendation is from NICE clinical guideline 66.

8

See NICE clinical guideline 87.

Copyright © 2009, National Institute for Health and Clinical Excellence.

All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the express written permission of NICE.

Bookshelf ID: NBK61845
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