PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
The appropriate insulin regimen for each patient with diabetes will depend on their type of diabetes and their individual needs and circumstances. Regimens which attempt to improve glycaemic control will require more active involvement of the patient, both with the number of injections and with the need for close self-monitoring of blood glucose. See the separate article on Diabetes Education and Self-management Programmes.
Insulin regimens should be tailored to the individual, taking into account the patient's type of diabetes, previous control, age, dexterity, eyesight, and personal and cultural preferences.
Insulin is usually injected into the upper arms, thighs, buttocks or abdomen. The absorption may be increased if the limb is used in strenuous exercise after the injection. Lipodystrophy can be minimised by using different injection sites in rotation. Local allergic reactions may occur but are rare.
Effective patient education for people using insulin treatment is essential, including 'sick day' guidance (see also the separate article on Diabetes and Intercurrent Illness). Insulin Passports and patient information booklets should be offered to patients receiving insulin.
Types of insulin
Insulins are classified according to their duration of action:
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- Rapid-acting insulin analogues - eg, insulin aspart, lispro and glulisine: these are genetically engineered analogues of human insulin. They aim to work like the insulin normally produced with a meal. Given subcutaneously, they have an onset of action of approximately 15 minutes, peak at 1 hour and last 3-4 hours. They can be injected shortly before, during or immediately after meals.
- Soluble insulins: these are the conventional short-acting insulins. Used subcutaneously, they have an onset of action of 30 minutes, peak at 2-3 hours and last 8 hours. They should be injected 30 minutes before meals. Short-acting insulins may also be given intravenously by pump (in hospital care). If used intravenously, the half-life is very short (a few minutes) and the insulin disappears by 30 minutes.
These have an onset of action of 2-4 hours, peak at 6-7 hours and last 20 hours. The standard intermediate-acting insulin is isophane insulin - also known as neutral protamine Hagedorn (NPH).
Isophane insulin is useful for initiation of twice-daily insulin regimens. Isophane insulin can be mixed with soluble insulin but ready-mixed preparations are available (biphasic isophane insulin, biphasic insulin aspart, or biphasic insulin lispro).
Long-acting insulin analogues (insulin detemir and insulin glargine)
These are also genetically modified analogues. They have an onset of action at 1-3 hours, then plateau and last for 20-24 hours. They are used once- or twice-daily, and achieve a steady-state to produce a constant level of insulin. This is physiologically similar to normal endogenous basal insulin secretion.
These are a mix of rapid- or short-acting insulin with intermediate-acting insulins, available in mixes of different proportions.
- Long- or intermediate-acting insulin is given at bedtime.
- It is suitable only for patients with type 2 diabetes and may be used in combination with oral hypoglycaemic agents.
- This regimen may be used when starting insulin in type 2 diabetes and when there is dependence on others to give injections.
- A biphasic insulin is injected twice a day (pre-breakfast and pre-evening meal).
- This assumes that the patient eats three meals per day.
- The peak action varies directly with the proportion of soluble insulin in the combination.
- It may be difficult to achieve optimal glycaemic control, and the regimen can be complicated by hypoglycaemic episodes.
- The peak and trough of the evening dose of longer-acting insulin can lead to the combination of nocturnal hypoglycaemia and then fasting hyperglycaemia in the morning.
The overlap of short-acting and long-acting insulin between meals means that additional snacks are often required to avoid hypoglycaemia. Using faster-acting insulin analogues instead of soluble insulin in the pre-mixed combination can reduce this problem.
- Intermediate- or long-acting insulin is given at bedtime to cover overnight insulin requirements.
- It is combined with rapid- or short-acting insulin injections to cover mealtimes. This offers greater flexibility and is the most commonly adopted method when intensified insulin therapy is used to provide optimal glycaemic control.
There may be hypoglycaemic episodes between meals and at night; again, use of fast-acting analogues instead of soluble insulin may reduce this problem.
Continuous subcutaneous insulin infusion, or insulin pump therapy
- Continuous subcutaneous insulin infusion (CSII) - insulin pump therapy - is where an adjustable basal infusion rate of insulin is given via an indwelling catheter, supplied from a syringe reservoir worn underneath the patient's clothing.
- The patient can then activate pre-meal boluses.
- Pumps can be disconnected for short periods (up to one hour) for activities such as swimming.
- They can be pre-programmed; for example, to compensate for nocturnal and early morning glucose fluctuations.
- The rate of insulin absorption from pumps is more predictable than with multiple subcutaneous injections.
- CSII provides some advantages over multiple daily injections (MDIs) in type 1 diabetes, both for children and adults.
- CSII is particularly useful for patients with recurrent hypoglycaemia, unpredictable lives, delayed meals or pre-breakfast hyperglycaemia.
The insulin used in pumps may be soluble or a fast-acting analogue. Note that there have been two anecdotal case reports of insulin lispro precipitating in pumps: if users have unpredictable glucose fluctuations, they should consider changing to aspart or soluble insulin.
National Institute for Health and Care Excellence (NICE) guidance for insulin pump therapy
Continuous subcutaneous insulin infusion (CSII, or ‘insulin pump’) therapy is recommended as a treatment option for adults and children aged 12 years and older with type 1 diabetes mellitus provided that:
- Attempts to achieve target HbA1c levels with MDI result in the person experiencing repeated and unpredictable occurrence of hypoglycaemia that results in persistent anxiety about recurrence and is associated with a significant adverse effect on quality of life; or
- HbA1c levels have remained high (8.5% or above) on MDI therapy despite a high level of care.
CSII therapy is recommended as a treatment option for children younger than 12 years with type 1 diabetes mellitus provided that MDI therapy is considered to be impractical or inappropriate. Children on insulin pumps would be expected to undergo a trial of MDI therapy between the ages of 12 and 18 years.
CSII therapy is not recommended for the treatment of people with type 2 diabetes mellitus.
Rapid-acting human insulin analogues
The rapid-acting human insulin analogues (insulin aspart, insulin glulisine and insulin lispro) have a faster onset and shorter duration of action than soluble insulin. The rapid-acting analogues are useful for:
- Those who wish to inject shortly before or immediately after meals (helpful for unpredictable meals or young children).
- Those prone to hypoglycaemia between meals.
- Those prone to nocturnal hypoglycaemia.
- Avoiding the need for snacks between meals.
When rapid-acting analogues are used as the mealtime bolus, NICE suggests that the basal insulin should be a long-acting analogue (rather than NPH insulin).
Long-acting human insulin analogues
These include insulin degludec, insulin detemir and insulin glargine.
NICE guidance for insulin glargineNICE has recommended that insulin glargine should be an option for patients with type 1 diabetes, and should be used when:
- Nocturnal hypoglycaemia is a problem on isophane (intermediate-acting) insulin.
- Morning hyperglycaemia on isophane insulin results in difficult daytime glucose control.
- Rapid-acting insulin analogues are used for mealtime blood glucose control.
- Require assistance with injecting their insulin; or
- Would otherwise need twice-daily insulin injections in combination with oral antidiabetic drugs; or
- Have a lifestyle significantly restricted by recurrent symptomatic hypoglycaemia.
Which regimen for which patient?
Type 1 diabetes
The options are:
- Twice-daily biphasic insulin.
- Basal-bolus regimen - this gives greater flexibility and can improve glycaemic control, but requires more injections.
- Insulin pump - see NICE guidance, above.
Type 2 diabetes
In type 2 diabetes, there is a gradual decline in beta cell function, so that treatment will need regular adjustment. When oral agents are insufficient options are:
- Basal insulin - this is often a suitable first step, using once- or twice-daily intermediate- or long-acting insulin.
- Twice-daily biphasic insulin.
- Basal-bolus regimen.
Oral hypoglycaemic agents are often used in combination with insulin:
- Metformin is usually continued.
- Sulfonylureas are often continued with a basal insulin regimen; however, if a bolus regimen is used, they should be gradually stopped.
Good glycaemic control is especially important both pre-conception and antenatally, to reduce fetal abnormalities and obstetric complications. Insulin must be continued for patients with type 1 diabetes and is often required in type 2 and gestational diabetes.
See also the separate article on Diabetes in Pregnancy.
Insulin management around surgery
See the separate article on Precautions with Patients with Diabetes Undergoing Surgery.
What is the evidence for new insulin therapies?
Overall, there is a lack of clear evidence regarding benefits and harms of the newer insulin therapies. As a summary, the evidence so far suggests that:
- Rapid-acting insulin analogues may improve postprandial hyperglycaemia and reduce hypoglycaemia.
- Long-acting insulin analogues may reduce nocturnal hypoglycaemia and weight gain, but some studies found them no better than conventional NPH insulin.
- Insulin pumps improve HbA1c values slightly overall, but seem to be of greater benefit to some patients, particularly those who previously had poorer glycaemic control.
- The newer treatments seem to be safe so far.
In practice, treatment should be tailored to the individual, taking into account lifestyle, preferences and personal patterns of glycaemic control. Whatever the regimen, patient education and involvement are crucial in achieving good results.
Further reading & references
- Management of diabetes; Scottish Intercollegiate Guidelines Network - SIGN (March 2010)
- Hyperglycaemia in acute coronary syndromes; NICE Clinical Guideline (October 2011)
- Diabetes (type 1 and type 2) in children and young people: diagnosis and management, NICE Guidance (Aug 2015)
- Diagnosis and management of type 1 diabetes in children, young people and adults; NICE Clinical Guideline (July 2004)
- British National Formulary; NICE Evidence Services (UK access only)
- The adult patient’s passport to safer use of insulin; NHS, March 2011
- Mooradian AD, Bernbaum M, Albert SG; Narrative review: a rational approach to starting insulin therapy. Ann Intern Med. 2006 Jul 18;145(2):125-34.
- Type 2 diabetes - newer agents (partial update); NICE Clinical Guideline (May 2009)
- Gough SC; A review of human and analogue insulin trials. Diabetes Res Clin Pract. 2007 Jul;77(1):1-15. Epub 2006 Nov 16.
- Cummins E, Royle P, Snaith A, et al; Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic evaluation. Health Technol Assess. 2010 Feb;14(11):iii-iv, xi-xvi, 1-181. doi: 10.3310/hta14110.
- Diabetes - insulin pump therapy: Continuous subcutaneous insulin infusion for the treatment of diabetes (review); NICE Technology Appraisal Guidance, July 2008
- Heine RJ, Diamant M, Mbanya JC, et al; Management of hyperglycaemia in type 2 diabetes: the end of recurrent failure? BMJ. 2006 Dec 9;333(7580):1200-4.
- Siebenhofer A, Plank J, Berghold A, et al; Short-acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003287.
- Horvath K, Jeitler K, Berghold A, et al; Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005613.
- Home PD, Rosskamp R, Forjanic-Klapproth J, et al; A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes. Diabetes Metab Res Rev. 2005 Nov-Dec;21(6):545-53.
- Retnakaran R, DeVries JH, Hanaire-Broutin H, et al; Continuous subcutaneous insulin infusion versus multiple daily injections: modeling predicted benefits in relationship to baseline A1c. Diabetes Care. 2005 Jul;28(7):1835-6.
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Dr Naomi Hartree
Dr Colin Tidy
Dr Adrian Bonsall