This new Guidelines summary for nurses covers principles for starting injectable therapies in adults with type 2 diabetes, including a step-by-step guide. For a complete set of recommendations, refer to the full guideline.
Reflecting on your Learnings
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Indications for Injectable Therapy
Glucagon-like Peptide 1 Therapy—Who May Benefit?
- The NICE guideline, Type 2 diabetes in adults: management, recommends that glucagon-like peptide 1 (GLP-1) therapy should be considered if triple therapy with metformin and two other oral drugs is not effective, not tolerated, or contraindicated
- NICE GLP-1 indications:
- a body mass index (BMI) of 35 kg/m2 or higher (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 lower than 35 kg/m2 and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
- GLP-1s have the benefit of not causing hypoglycaemia unless they are used in conjunction with a drug that can cause this independently, for example, sulfonylureas.
Which Patient Groups are Not Suitable for GLP-1 Therapy?
- People with type 1 diabetes—can be used off-label in certain individuals with an elevated BMI
- Acute pancreatitis
- Severe gastrointestinal disease
- Pregnant or nursing mothers
- End-stage renal failure (chronic kidney disease stage 5; estimated glomerular filtration rate [eGFR] less than 15 ml/min)
- History of alcoholism
- Low BMI.
Insulin Therapy—Who May Benefit?
- Insulin is likely to be required in up to 50% of patients with type 2 diabetes. It may be a temporary or permanent treatment choice
- Insulin is being used increasingly as a temporary treatment for patients with:
- severe hyperglycaemic symptoms
- infection causing hyperglycaemia not controlled on oral therapy
- after myocardial infarction or other vascular episode (coronary artery bypass graft, peripheral bypass, cerebral vascular event)
- patients on steroids
- acutely unwell patients pre- and post-surgery
- It is important to record why insulin was started and to reassess whether insulin is still needed
- Insulin should be considered as a ‘permanent’ treatment for:
- when dual therapy has not continued to control glycated haemoglobin (HbA1c) to below the person’s individually agreed threshold, also consider insulin-based therapy (with or without other drugs)
- people with suboptimal glycaemic control (58–75 mmol/mol) who are at high risk of complications through young age or who have established microvascular or macrovascular complications
- Other indications for insulin therapy may include:
- personal preference
- painful neuropathy
- foot ulceration and infection
- enteral feeding
- ketosis prone diabetes
- pregnancy or planning pregnancy
- recurrent fungal or bacterial infections
- people who cannot tolerate oral hypoglycaemic drugs.
Which Patient Groups are not Suitable for Insulin Therapy?
- It is not always obvious who will do well and who won’t. Age in itself is not a bar to insulin. Elderly patients often derive substantial symptomatic benefit and manage injections without difficulty. A ‘trial’ of insulin is appropriate for some people
- the success of the intervention must be examined at regular intervals
- if there is no benefit from insulin or there are side effects, for example, significant hypoglycaemia or marked weight gain, it could be stopped
- people who have type 2 diabetes and who are frail will not always benefit from a low HbA1c target (for example less than 53 mmol/mol). Aiming for a target such as this may place frail patients at risk of hypoglycaemia and subsequent falls/hospital admission. Targets should be adjusted accordingly
- people with other physical or mental health problems living with minimum or no support
- people who are not concordant with oral hypoglycaemic agents (OHAs) will not suddenly start taking injectable therapy. The underlying reasons for non-concordance should be discussed with the patient first before further intensification of treatment. Consider slow-release versions of OHAs that can be taken once daily that may improve the situation
- individuals with alcoholism who are actively drinking alcohol (hypo risk) and those who are self-harming.
Table 1: Is the Patient Likely to Benefit from Insulin?
|Likely to Benefit||May not Benefit|
|Marked symptoms||No symptoms|
|Slim and losing weight||Overweight and gaining|
|Well motivated||Poorly motivated|
|Careful with diet||Not careful with diet|
|Established complications and/or long life expectancy||No complications and limited life expectancy|
Starting Insulin Treatment
- As part of patient education, insulin therapy should be discussed as a treatment option from diagnosis onwards. The emphasis should be placed on the pancreas that is not able to cope with demand and not that the individual has failed
- Insulin treatment should not be used as a threat to improve diabetes management.
For information on when people don’t want insulin therapy and how injectable therapies work, refer to the full guideline.
Choosing the Right Injectable Therapy
Who Makes the Decision about Starting Injectable Therapies?
- Your role is to explain the options and present all the ‘pros and cons’. The final decision must be made by the person themselves. To carry out your role, you will need to understand:
- indications for GLP-1 analogue therapy for type 2 diabetes
- what is a GLP-1 analogue
- GLP-1 analogue treatment options
- how GLP-1 works
- the GLP-1 analogue delivery devices
- the principles of normal insulin production
- the types of insulin available
- why insulin is needed
- how insulin works
- common insulin regimens
- the benefits and disadvantages of the various delivery devices
- When starting insulin therapy in adults with type 2 diabetes, continue to offer metformin for people without contraindications or intolerance and review the continued need for other blood glucose lowering therapies
- There could be some advantages to combining insulin/GLP-1 with OHAs. These include:
- less risk of weight gain
- less risk of hypoglycaemia
- a simpler treatment regimen
- better glycaemic control while insulin/GLP-1 are being introduced and the dosage adjusted
- cardiovascular benefits
- The criteria for continuing and withdrawing OHAs when insulin is introduced are clearly stated in the NICE guideline on type 2 diabetes in adults. These should be utilised alongside this document to aid clinically appropriate decision making.
GLP-1 Treatment Options
- There are eight injectable GLP-1 analogues currently available and are used as a treatment option for people with type 2 diabetes.
Table 2: GLP-1 Treatment Options
|Dulaglutide (Trulicity®)||0.75 mg once weekly/1.5 mg once weekly|
|Exenatide (Byetta®)||5 mcg twice daily/10 mcg twice daily|
|Exenatide extended release (Bydureon®)||2 mg once weekly|
|Liraglutide (Victoza®)||0.6 mg initially, can be increased up to 1.2/1.8 mg once daily|
|Lixisenatide (Lyxumia®)||50 mcg /100 mcg|
0.25 mg weekly for 4 weeks and then increase to 0.5 mg once weekly. It can be increased to 1 mg once weekly thereafter if further glycaemic control is needed. Semaglutide is also available in an oral formulation (Rybelsus)
|Tirzepatide (Mounjaro®)[A]||Initially 2.5 mg once weekly for 4 weeks, then increased to 5 mg once weekly for at least 4 weeks, then increased if necessary up to 15 mg once weekly. Dose to be increased in steps of 2.5 mg at intervals of at least 4 weeks|
|[A] Note: Tirzepatide received marketing authorisation in October 2022, after the publication of the update to NICE Guideline 28. For more information on tirzepatide, please refer to the British National Formulary.|
Which Insulin Regimen?
- There are many different insulin regimens available. These are used to suit varying requirements/individual needs of the person living with diabetes. There is no one right choice and one regimen may not necessarily continue. If unsuitable, the regimen requires to be changed.
- Insulin preparations can be broadly categorised into the following groups based on their time action profiles. The duration of action of each particular type of insulin could vary from one patient to another, therefore needs should be assessed individually:
- ultra-rapid acting insulins
- rapid-acting insulins
- short-acting insulin
- intermediate-acting insulins
- fixed mixtures
- long-acting insulin
- ultra-long-acting insulin
- insulin and GLP-1 combination; (Xultophy®).
Usual Strength Insulin 100 units/ml
- All insulin is available in a concentration/strength of 100 units/ml. This should be the most commonly prescribed insulin strength and always used for new insulin starts.
- Some manufacturers have developed insulin with a higher strength formulation, for example, 200 units/ml and 300 units/ml. These offer the same insulin action but in less volume, and can be very useful for patients on doses >40 units to help with insulin absorption and lower the risk of lipohypertrophy
- These insulins only are available in pre-filled pens to ensure that the correct dose: volume concentration is given. The patient still dials to the same dose but a different volume is given.
Table 3: Higher-Strength Insulin Preparations
|Insulin Preparation/Time Action Group||Insulin Name||Strength Available||Volume Injected|
|Ultra-rapid acting||Lyumjev||200 units/ml||This is double the concentration of 100 units/ml. Therefore half the volume is injected|
|Rapid acting||Humalog||200 units/ml||This is double the concentration of 100 units/ml. Therefore half the volume is injected|
|Ultra-long acting||Tresiba||200 units/ml||This is double the concentration of 100 units/ml. Therefore half the volume is injected|
|Ultra-long acting||Toujeo (insulin glargine)||300 units/ml||This is three times the concentration of 100 units/ml. Therefore one third of the volume is given|
- These high strength insulins will be primarily initiated by specialist services but general practice will be required to provide prescriptions for them. Always ensure that anyone prescribed these higher concentration insulins has been given the following advice:
- ✓ always check the name and strength of insulin that they have been given before they leave the pharmacy
- ✓ always carry their insulin passport or insulin safety card with them
- ✖ never use a syringe to withdraw the insulin from the pre-filled pen device.
For information on recommended insulin regimens, refer to the full guideline.
A Step-by-Step Guide to Starting Injectable Therapies
- Identify your own barriers:
- lack of preparation
- keeping up to date
- Check the Integrated career and competency framework for diabetes nursing (TREND-UK, 5th edition, 2019) to identify the competences required for starting insulin. Make sure you understand exactly what’s involved
- Is this within the scope of your professional practice? If not, seek help and supervision. Spend time with a diabetes specialist nurse and observe some insulin and GLP-1 starts
- The Royal College of Nursing (RCN) recommends that that relevant e-learning modules on the safe use of insulin and Cambridge Diabetes Education Programme are completed.
Areas to Discuss with Your Patient
- If they are still reluctant to start an injectable therapy, suggest a 3-month trial period; experience shows that very few people want to stop a treatment once they have started but the idea of using it ‘for life’ can be daunting
- If they refuse outright, you must respect their choice. It may be worth encouraging them to talk to someone who has already started insulin or GLP-1 and is doing well
- Have you done a dummy injection? Many people think they will have to use a large needle and inject into a vein. It’s important to allay their fears and show them how easy and painless injecting can be. They will then be able to concentrate on the rest of the discussion
- Ensure that your documentation includes any refusal/delay for treatment.
Dealing with Dummy Injections
- Talk to the person about undertaking a ‘dummy’ injection and reassure that it is not as bad as they expect. Understand that with type 2 diabetes the person may have pre-conceived ideas of what injecting is like, as a family member or friend may have used insulin in the past
- Ask the person if they would be willing to simply insert a needle for a ‘dry run’. It can be reassuring for people to try this soon after diagnosis, long before injectable treatment is actually required
- Note: A dummy injection is purely for the patient to feel the insertion of the needle and how to handle an insulin/GLP-1 pen. The saline fluid contained in the pen device should never be injected into the person. The pen device should be disposed of after the demonstration to avoid cross-patient contamination.
First Appointment, First Injection
- As a general guide, you should allow between 30 and 60 minutes for the first appointment. The amount of time you need will depend on the complexity of the chosen regimen and the individual person’s capabilities, for example, culture, language, mental capacity, health beliefs
- You will need to cover the following points:
- agree a date and time for the first injection—some may wish to postpone it, for example, until after a holiday, or after Ramadan
- agree a place—injectable therapy starts can take place in an outpatient clinic, on a hospital ward, at a GP surgery, or in the person’s home; you can start people individually, or in groups
- encourage them to bring a partner or friend; most people will manage their injections themselves but some will need support from a partner, carer, or district nurse
- discuss whether or not they plan to carry on taking OHAs
- practice nurses can provide further support about dietary intake and how carbohydrate can affect the glucose levels. Referral to a diabetes specialist dietitian can be useful to increase that knowledge further with advice on portion control and avoiding large variations on a daily basis to improve glucose levels.
- Ideally, the first injection should be near the beginning of the week so the person is fairly confident before the weekend. This is because only emergency cover is available in most areas at weekends. Appropriate support for the person with diabetes will be difficult to find
- Telephone them the day after their first injection, and see them as often as necessary, gradually spacing out the appointments as their confidence grows.
Choosing a Delivery Device
Injection Devices for GLP-1
- All GLP-1 therapies are dispensed in disposable devices:
- once and twice-daily preparations are in disposable pen devices which contain 2–4 weeks’ treatment
- Trulicity® once-weekly preparation is in a single use pen device
- Ozempic® once-weekly preparation is in a disposable device that lasts for four injections (1 month)
- the once-weekly preparation of exenatide (Bydureon®) needs to be reconstituted prior to administration and it is therefore essential that this process is clearly explained to the patient. Demonstration packs are available from the manufacturers to facilitate this process.
Insulin Injectable Devices
- There are two main types of injection devices on the market. Some ‘pens’ come pre-loaded with insulin and are known as ‘pre-filled’ pens. They cannot be re-used once they are empty of insulin and the whole pen is disposed in a sharps bin. Others use cartridges of insulin that are inserted into a reusable device. Pre-filled injection devices can be easier to use. All cartridge pens are available on prescription. Refer to the most current edition of the British National Formulary or online electronic medicines compendium
- Give people the chance to try out different devices and involve them in the final decision. You must take into account the person’s manual dexterity—how heavy is the pen and how easy it is to push in the insulin or GLP—and the size of dose they are likely to need. Some devices will deliver a bigger maximum dose than others
- If the person is visually impaired, you should also consider:
- whether the pen has an audible click on dialling
- the size of the numbers on the dial
- whether appropriate magnifiers are available
- People with a fear of needles may prefer to use needles such as the auto shield safety needle, where the needle is not exposed during the injection.
- Trend UK Injection Technique (2018) recommends that needles longer than 4 mm can contribute to problems with insulin delivery, leading to glycaemic variations which may contribute to unexplained hypoglycaemia and/or above target HbA1c.
Teaching Injection Technique
- TREND UK Injection Technique (2018) recommends the following steps:
- observe the person assemble the pen, attach the needle, dial the dose, perform a test/air shot, and give the injection themselves
- an ‘air shot’ will make sure the plunger is connecting and expels air from the pen. You may need to guide them—but don’t do it for them. Use the product information leaflet which comes with the pen device as a tool to guide the teaching process. Ensure the needle is viable. (Trulicity® does not need an ‘air shot’. GLP-1s only need priming once)
- if using cloudy insulin, invert or rotate (‘rock n roll’) the pen at least ten times in the palm of the hands and invert ten times to mix the insulin
- show the patient how to check expiry dates before administration
- inject into clean skin with clean hands. Alcohol wipes are not recommended. Alcohol is an astringent and can make the injection more painful, as well as hardening the skin
- choose injection sites. Insulin should be injected into subcutaneous fat, not muscle. To avoid intramuscular injection, slim people, or those using injection sites without much subcutaneous fat, should use a lifted skin fold
- inject the insulin slowly, and once the plunger is fully depressed, leave the needle in the skin for 10 seconds
- Occasionally, there may be bleeding after the needle is withdrawn. Reassure the person, and advise them to apply gentle pressure for a couple of minutes to minimise bruising. They should not rub the area, as deep massage for several minutes may increase the rate of insulin absorption.
Choosing an Injection Site
- There are a number of alternatives:
- abdomen—fastest absorption, usually plenty of subcutaneous fat, making it easy and a good option for fast-acting insulin. Can be the site with the most consistent rate of absorption and it is less affected by physical activity
- thighs—slower absorption, best with intermediate-acting insulin or the evening dose of a twice-daily insulin regimen; very little subcutaneous fat laterally
- back of arms—medium-to-fast absorption, make sure there is sufficient fat and use short needles
- buttocks—slowest absorption, use for intermediate- or long-acting insulins; plenty of subcutaneous fat
- The above information applies only to human insulin; the absorption of analogue insulin is not affected by the injection site used.
Rotating Injection Sites
- Repeatedly injecting into the same small area will cause lumps (lipohypertrophy) which hinder insulin absorption resulting in unstable blood glucose levels, and can be unsightly
- Alternate between the left and right side on a weekly basis, and rotate sites within the same area. Each injection should be at least a finger’s breadth away from the last one
- Check for lumps on a regular basis. If lipohypertrophy is found, that area should not be used for injection until it has become soft again. This may take weeks or even months, depending on the severity of the lipohypertrophy.
- All GLP-1 analogues are injected into the subcutaneous fat layer in the same way as insulin is administered.
- GLP-1 treatment does not induce hypoglycaemia, but when used in combination with sulfonylurea therapy the risk of hypoglycaemia secondary to sulfonylurea treatment will be increased. The essential education (see the full guideline) should therefore be covered for patients commencing GLP-1 therapy in combination with a sulfonylurea.
- The common side effects of GLP-1 therapy are nausea and vomiting which should resolve after 7–10 days. Side effects can be minimised by starting at the lowest dose recommended and titrating the dose after 4 weeks and injecting immediately prior to food. Patients using the once-weekly preparation of exenatide may complain of pea-sized lumps at the site of their injection; these lumps should resolve spontaneously after approximately 6 weeks
For information on insulin doses, storage, and checklists, refer to the full guideline.