Type 2 diabetes mellitus treatment guidance

Target HbA1c levels

Involve adults with type 2 diabetes in decisions about their individual HbA1c target. Agree an individualised HbA1c target based on the person's needs and circumstances. Encourage them to achieve the target and maintain it unless any resulting adverse effects (including hypoglycaemia), or their efforts to achieve their target, impair their quality of life. The benefits of tight blood glucose control are not immediate, but accrue over years to decades. It is important to explain this to patients. NICE have produced a patient decision aid which is designed to help individual patients participate in decision making about target HbA1c levels. It summarises information on the things people most often want to think about when they are deciding on what new target HbA1c level is best for them.

The NICE guideline states that a target HbA1c level of 48 mmol/mol is recommended for adult patients with type 2 diabetes managed either by lifestyle and diet, or by lifestyle and diet combined with a single drug not associated with hypoglycaemia. For adults on a drug associated with hypoglycaemia, aim for an HbA1c level of 53 mmol/mol.

If HbA1c levels are not adequately controlled by a single drug and rise to 58 mmol/mol or higher:

• reinforce advice about diet, lifestyle and adherence to drug treatment and
• support the person to aim for an HbA1c level of 53 mmol/mol and
• intensify drug treatment (see drug treatment guidance below)

Consider relaxing the target HbA1c level on an individual basis, with particular consideration for people who are older or frail that may be unlikely to achieve longer‑term risk‑reduction benefits and perhaps have a reduced life expectancy, or if tight blood glucose control poses a high risk of the consequences of hypoglycaemia, for example patients with increased fall risk, and patients who drive or operate machinery as part of their job. Due consideration should also be given to people who have impaired awareness of hypoglycaemia, and those with significant comorbidities.

Patients diagnosed at a younger age (e.g. under 55) should aim for strict NICE targets, unless there are strong reasons not to (such as hypoglycaemic episodes or occupation). Patients with microvascular complications (especially albuminuria or retinopathy) should also normally aim for strict NICE targets. For patients with life expectancy less than 5-10 years or who are vulnerable to hypoglycaemia, it would be reasonable to raise the HbA1c targets by around 10 mmol/mol. Patients with less than 1-2 years life expectancy should be treated primarily for symptom control.

If adults with type 2 diabetes achieve an HbA1c level that is lower than their target and they are not experiencing hypoglycaemia, encourage them to maintain it. Be aware that there are other possible reasons for a low HbA1c level, for example, deteriorating renal function or sudden weight loss.

Frequency of monitoring HbA1c

In adults with type 2 diabetes, measure HbA1c levels at:

• 3–6-monthly intervals (tailored to individual needs), until the HbA1c is stable on unchanging therapy
• 6-monthly intervals once the HbA1c level and blood glucose lowering therapy are stable.

Do not routinely offer self-monitoring of blood glucose levels for adults with type 2 diabetes unless the person is on insulin, on oral medication that may increase their risk of hypoglycaemia, is pregnant or planning to become pregnant, or if there is evidence of hypoglycaemic episodes.

Consider short-term self-monitoring of blood glucose levels in adults with type 2 diabetes (and review treatment as necessary), when starting treatment with oral or intravenous corticosteroids or to confirm suspected hypoglycaemia.

NICE recommends that an individualised approach to diabetes care is adopted, tailored to the needs and circumstances of adults with type 2 diabetes, taking into account their personal preferences, comorbidities, risks from polypharmacy, and their ability to benefit from long-term interventions because of reduced life expectancy. Such an approach is especially important in the context of multi-morbidity.

Clinicians may offer a 3-6 month trial of lifestyle and diet interventions before commencing drug treatment, although for some patients it may be appropriate to begin treatment with metformin at diagnosis.

Optimum cardiovascular risk factor reduction should be undertaken alongside intensification of blood glucose lowering therapies. Control of BP, lipids and other lifestyle factors (e.g. smoking cessation) will have a larger impact on risk reduction than tight blood glucose control.

At each review reassess the person's needs and circumstances, checking diet and compliance with existing therapies before escalation; if a patient's attention to diet and lifestyle has lapsed since the last review the HbA1c may show no change even if the medication is working. Consider stopping any medicines that are not effective. The importance of adherence to drug treatment, once commenced, should be reinforced. Intensification of therapy may be considered on average 3 months after making a change and guided by repeat HbA1c. This needs to be flexible according to clinical circumstances e.g. sooner intensification may be consider in more acute symptomatic hyperglycaemia and can be guided by blood glucose monitoring results rather than HbA1c. In patients with poorly controlled diabetes, if HbA1c remains high at 3 months, it is unlikely that significant further improvement will be seen at 6 months.

The management of adult patients with type 2 diabetes is separated into two treatment pathways:

• Patients who can take metformin
• Patients in whom metformin is contraindicated or not tolerated

For adults with type 2 diabetes, discuss the benefits and risks of drug treatment, and the options available.

Base the choice of drug treatment(s) on:

• the effectiveness of the drug treatment(s) in terms of metabolic response
• safety and tolerability of the drug treatment(s)
• the person's individual clinical circumstances, for example, comorbidities, risks from polypharmacy
• the person's individual preferences and needs
• the licensed indications or combinations available
• cost (if 2 drugs in the same class are appropriate, choose the option with the lowest acquisition cost)

Rescue therapy at any phase of treatment:

If an adult with type 2 diabetes is symptomatically hyperglycaemic, consider insulin or a sulfonylurea, and review treatment when blood glucose control has been achieved.

If HbA1c rises to 48mmol/mol after 3-6 months of diet and lifestyle intervention, commence monotherapy.

Monotherapy

See 6.1.2 Antidiabetic drugs

Metformin

• Standard-release should be given first line; titrate dose slowly to minimise gastrointestinal side effects.
• If a patient experiences gastrointestinal side effects with standard-release, give consideration to a trial of modified-release metformin.
• Modified-release metformin should not be used in preference to immediate-release metformin.
• Support patients, who continue to use metformin monotherapy, in aiming for an HbA1c level of 48mmol/mol.

If metformin not tolerated, go to: Adult with type 2 diabetes who cannot take metformin

First Intensification

If HbA1c rises to 58mmol/mol, consider adding one of the following options to metformin; support the patient to aim for an HbA1c level of 53mmol/mol.

Drugs should be introduced in a stepwise manner, checking for tolerability and effectiveness of each drug.

See 6.1.2 Antidiabetic drugs

Metformin and Dipeptidylpeptidase-4 inhibitor (DPP-4 inhibitor)

Or

Metformin and Pioglitazone

Or

Metformin and Sulfonylurea

Or

Metformin and Sodium-glucose co-transporter-2 (SGLT2) inhibitor

• Canagliflozin, dapagliflozin or empagliflozin in combination with metformin is recommended only if a sulfonylurea is contraindicated or not tolerated, or the person is at significant risk of hypoglycaemia or its consequences.
• See NICE Technology Appraisal Guidance:TA315, TA288 and TA336

If HbA1c rises to 58mmol/mol, go to second intensification.

Second Intensification

Patients whose HbA1c reaches 58mmol/mol despite dual therapy, consider triple therapy; support the patient to aim for an HbA1c level of 53mmol/mol.

Drugs should be introduced in a stepwise manner, checking for tolerability and effectiveness of each drug.

See 6.1.2 Antidiabetic drugs

Metformin and DPP-4 inhibitor and sulfonylurea

Or

Metformin and pioglitazone and sulfonylurea

Or

Consider starting Insulin based treatment

• Only if triple therapy with metformin and 2 other oral drugs is not effective, not tolerated or contraindicated, consider combination therapy with metformin, a sulfonylurea and a glucagon-like peptide-1 (GLP-1) mimetic (exenatide, liraglutide, lixisenatide) for adults with type 2 diabetes who:
  • have a BMI of 35kg/m² or more (adjust accordingly for people from black, Asian and other minority ethnic groups) and specific psychological or other medical problems associated with obesity or
  • have a BMI less than 35kg/m² but insulin therapy would pose significant occupational problems, or weight loss would benefit other significant obesity-related comorbidities.

Treatment with combinations of medicines including SGLT-2 inhibitors may be appropriate for some people with type 2 diabetes:

Metformin and sulfonylurea and SGLT-2 inhibitor

Or

Metformin and pioglitazone and SGLT-2 inhibitor

See NICE Technology Appraisal Guidance: TA315, TA288 and TA336 for the use of SGLT-2 inhibitors

NICE notes that metformin is contraindicated or not tolerated in approximately 15% of individuals.

If HbA1c rises to 48mmol/mol after 3-6 months of diet and lifestyle intervention, commence monotherapy.

Monotherapy

Consider one of the following:

• See 6.1.2 Antidiabetic drugs

DPP-4 inhibitor

• Support the patient to aim for a target HbA1c level of 48mmol/mol

Or

Pioglitazone

• Support the patient to aim for a target HbA1c level of 48mmol/mol

Or

Sulfonylurea

• Support the patient to aim for a target HbA1c level of 53mmol/mol

Or

SGLT-2 inhibitors

• NICE TA390: Canagliflozin, dapagliflozin and empagliflozin as monotherapies are recommended as options for treating type 2 diabetes in adults for whom metformin is contraindicated or not tolerated and when diet and exercise alone do not provide adequate glycaemic control, only if:
  • a dipeptidyl peptidase-4 inhibitor would otherwise be prescribed and
  • a sulfonylurea or pioglitazone is not appropriate

First Intensification

If HbA1c rises to 58mmol/mol, consider dual therapy.

Drugs should be introduced in a stepwise manner, checking for tolerability and effectiveness of each drug.

See 6.1.2 Antidiabetic drugs

DPP-4 inhibitor and Pioglitazone

• Support the patient to aim for a target HbA1c level of 53mmol/mol

Or

DPP-4 inhibitor and sulfonylurea

• Support the patient to aim for a target HbA1c level of 53mmol/mol

Or

Pioglitazone and sulfonylurea

• Support the patient to aim for a target HbA1c level of 53mmol/mol
• A lower dose of sulphonylurea may be needed.

Second Intensification

For patients whose HbA1c reach 58mmol/mol despite dual therapy, consider:

• See 6.1.2 Antidiabetic drugs

Insulin based treatment

• Support the patient to aim for a target HbA1c level of 53mmol/mol

When starting insulin, use a structured programme and continue to offer metformin for people without contraindications or intolerance. Review the continued need for other blood glucose lowering therapies.

Canagliflozin, dapagliflozin or empagliflozin in combination with insulin with or without other antidiabetic drugs may be recommended as an option for treating type 2 diabetes.

Only offer insulin and a GLP-1 mimetic with specialist care advice and ongoing support from a consultant-led multidisciplinary team.

Start insulin therapy for adults with type 2 diabetes from a choice of a number of insulin types and regimens:

• Offer isophane insulin (NPH) once or twice daily according to need.
• Consider starting both isophane (NPH) and short-acting insulin (particularly if the person's HbA1c is 75 mmol/mol or higher), administered either:
  • separately or
  • as a pre-mixed (biphasic) human insulin preparation.
• Consider as an alternative to isophane insulin (NPH), using insulin detemir or glargine if:
  • the person needs assistance to inject insulin,
  • the person's lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes or
  • the person would otherwise need twice-daily isophane insulin (NPH) in combination with oral blood glucose lowering drugs.
• Consider pre-mixed (biphasic) preparations that include short-acting insulin analogues, rather than pre-mixed (biphasic) preparations that include short-acting human insulin preparations, if:
  • the person prefers injecting insulin immediately before a meal
  • hypoglycaemia is a problem or
  • blood glucose levels rise markedly after meals.

Consider switching to insulin detemir or insulin glargine from isophane insulin (NPH) in adults with type 2 diabetes:

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

Monitor adults with type 2 diabetes who are on a basal insulin regimen (Isophane insulin [NPH], insulin detemir or insulin glargine) for the need for short-acting insulin before meals (or a pre-mixed [biphasic] insulin preparation).

Monitor adults with type 2 diabetes who are on pre-mixed (biphasic) insulin for the need for a further injection of short-acting insulin before meals or for a change to a basal bolus regimen with isophane insulin (NPH) or insulin detemir or insulin glargine, if blood glucose control remains inadequate.

NICE have produced a patient decision aid aimed at helping adults with type 2 diabetes think about their options for controlling their blood glucose to try to reduce the long-term risks of diabetes. The decision aid is intended to help adults with type 2 diabetes at the first intensification of drug treatment. It is not intended for use at other stages in the care pathway, or for women with type 2 diabetes who are pregnant or planning to become pregnant. It summarises information on the things people most often want to think about and discuss with their healthcare team when they are deciding on what new target HbA1c level is best for them, and which medicines they might try to achieve this target.

Primary prevention

Do not offer antiplatelet therapy (aspirin or clopidogrel) for adults with type 2 diabetes without CVD

Secondary prevention

All patients with diabetes and a history of CVD should receive antiplatelet therapy (see section 2.9 Antiplatelet drugs).

Patients with Type 2 diabetes should have their lipids managed in line with the advice in Chapter 2 of the formulary.

Patients with Type 2 diabetes should have hypertension managed in line with the advice provided in Chapter 2 of the formulary.