The use of insulin can improve glycaemic control in most people, but any benefits need to be balanced against increased risks of hypoglycaemia and possible weight gain.26
International and Australian guidelines suggest considering a GLP-1 RA before commencing insulin, unless a person has extreme hyperglycaemic symptoms or an HbA1c of >11%.31 GLP-1 RAs are associated with weight loss as well as sparing insulin dose. Limitations to this approach include cost, possible side effects of GLP-1 RAs (nausea), and TGA or PBS restrictions on GLP-1 RA use in combination with other therapy that do not apply to insulin.
Side effects of insulin therapy
Rare adverse events associated with the use of insulin have been reported in observational studies. Such events include congestive heart failure, oedema, lipodystrophy, allergic reactions, reversible transaminitis, reversible nephrotic syndrome and ß-cell destruction.32
Common side effects include hypoglycaemia and weight gain. Risk factors for hypoglycaemia include:
- inappropriate dose
- timing or type of insulin (refer below)
- incorrect injection technique (eg injecting insulin intramuscularly, rather than subcutaneously, can increase absorption rates by 50%)
- missing meals, or meals with no or insufficient carbohydrate
- alcohol intake
- exercise or unplanned physical activity
- weight loss
- treatment with agents potentiating hypoglycaemia (eg sulfonylureas)
- decreased insulin clearance (eg renal failure)
- changes to other medications (eg reducing or ceasing steroids).
Strategies for preventing hypoglycaemia in patients include education about hypoglycaemic symptoms, structured self-monitoring of blood glucose (SMBG), discussing and individualising glycaemic goals, and continued team-based support.32
Weight gain is variable on initiation of insulin and may accompany initial titration such that weight gain may eventually level off. Slower titration can lead to slower weight gain.
Strategies to address weight include:
- referral to a credentialled diabetes educator (CDE) and/or accredited practising dietitian (APD)
- review of other clinical conditions that may impact glycaemic control, such as depression, occult malignancy, thyroid disease
- review of medications that may contribute to weight gain
- advice on increasing physical activity.
Early insulin intervention
Guidelines outlining the use of insulin in acute hyperglycaemic emergencies (including ketosis-inducing and hyperosmolar crises) are available.33,34 The use of insulin in these cases may be life-saving, and reassessment of long-term use can occur on metabolic stabilisation.
Refer to Appendix 1. Types of insulin available.
Insulin delivery options
A range of devices are available to deliver insulin, including insulin pens, syringes and pumps. Choice will depend on patient preference, need and ability to self-manage injections. A CDE or a diabetes nurse practitioner can help provide patient support.
Insulin pens are the most common way of administering insulin, as they make multiple daily injection schedules much easier and allow people to be more flexible in their self-management.
There is mounting evidence of selective beneficial effects of using insulin pumps and insulin patch pumps in people with type 2 diabetes – refer to the section ‘Use of technology in type 2 diabetes management’.
The National Diabetes Services Scheme (NDSS) provides subsidised access to insulin pump consumables for people with type 1 diabetes. For people with type 2 diabetes, some health funds cover insulin pumps, but consumables need to be self-funded.
Recommendations for delivery of insulin and non-insulin injectable medications
Using the correct delivery technique to ensure the optimal effect of insulin and GLP-1 RAs is critical to achieving optimal control of diabetes and reducing the risk of some adverse effects of injectable medications.
The following recommendations for insulin delivery are based on the Forum for Injection Technique and Therapy Expert Recommendations (FITTER).35
- Single use of pen needles and syringes is recommended (lipohypertrophy has been associated with reuse of pen needles and syringes).
- Shorter (size 4 mm or shortest available) needles applied to either the abdomen, thigh or buttock are adequate for most adults using insulin pen devices and will lessen the risk of intramuscular injection.
- Lipohypertrophy and lipodystrophy may occur with repeated insulin injections into the same site, and this can affect insulin absorption. This problem is overcome by ensuring rotation of injection sites.
Full recommendations are available on the Mayo Clinic website.
More information can be found in the Australian Journal of General Practice (AJGP) article ‘Teaching patients with type 2 diabetes to self-administer insulin’.36
When should patients start insulin?
General practitioners (GPs) should anticipate and proactively address the patient’s (and their own) reluctance to start insulin therapy. Early after a diagnosis of diabetes, it is important to discuss with patients that insulin may be used at some point to manage their diabetes.
With the appropriate insulin regimen, insulin therapy can be well managed in general practice, with patients achieving better HbA1c control, fewer hypoglycaemic episodes and less weight gain, thus alleviating many patient concerns.37
Insulin is one of the most effective glucose-lowering agents for type 2 diabetes, and can be titrated to suit the individual patient’s requirements. Commencement should not be delayed if hyperglycaemia and symptoms cannot be controlled adequately by a patient’s existing treatments. Recent evidence suggests that people who decline treatment with insulin when it is recommended to them can take longer to achieve HbA1c targets.38
Importantly, insulin is not the end of the road for the person with diabetes, nor does it represent therapeutic or patient failure.
Insulin should be initiated in patients with type 2 diabetes who are taking maximal doses of non-insulin glucose-lowering medicines and who have suboptimal glycaemic control (HbA1c or blood glucose above individualised target), whether they are asymptomatic or symptomatic.31,39
Insulin therapy may remain an alternative for older or nursing home patients, even in end-of-life care, with HbA1c >9% (75 mmol/mol), especially if control of symptomatic hyperglycaemia is difficult.
Before starting insulin
Ensure that other possible causes of hyperglycaemia have been addressed (eg lifestyle, non-adherence to non-insulin glucose lowering medicines, other medications or medical conditions).40
Discuss with patients the benefits and costs of using insulin for better glycaemic control. Referral is recommended to a CDE and/or APD to provide the necessary support and education to the person with diabetes in the lead-up to insulin initiation.
A GP or CDE can complete the NDSS medication change registration form to allow patients to access syringes or pen needles through the NDSS scheme.
The NDSS has an information booklet for people with type 2 diabetes who are starting insulin.
Initial management planning and education (with both patients and carers) should cover:
- self-management – timing and frequency of SMBG, timing of meals, dose adjustment
- the impact of diet, in particular carbohydrate content (both type and amount)
- the effects of altered eating patterns, such as for religious fasts or weight loss strategies (eg intermittent fasting, 5:2 diets, very-low-calorie diets)
- the impact of physical activity
- hypoglycaemia management
- insulin delivery techniques (Box 1)
- weight management and the mitigation of weight gain with insulin therapy
- sick day management (refer to the section ‘Managing risks and other impacts of type 2 diabetes’)
- exercise, illness and travel considerations
- identification, roads and maritime services notifications.
This should be followed up regularly with structured education sessions.
Box 1. Insulin delivery
Fundamental information for patients about insulin delivery includes:
- insulin can be stored at room temperature for up to one month
- pre-mix insulin must be resuspended prior to each use
- insulin pen needles should be used only once, as re-use increases the risk of lipohypertrophy41
- when using a new insulin pen needle, use 1–2 units to expel air prior to dialling up the prescribed dose
- the abdomen is the preferred site for injecting
- insulin needs to be injected only into subcutaneous tissue – injecting into muscle can not only be painful, but can increase the absorption rate of insulin42
Patients should also be educated about:
- how to safely dispose of used needles
- how to rotate injection sites – patients should be taught and provided with an easy-to-follow injection site rotation plan, reviewed regularly, to reduce risk of lipohypertrophy43
- how to time insulin injections
- the importance of regular inspection of injection sites.
All insulins can work effectively.37 Selecting an insulin for initiation will depend on patient as well as disease characteristics. At the selection of the insulin preparation, consider which injecting device is most suitable for the patient.
Set an individualised target (refer to the section ‘Glucose monitoring’), following the principle of ‘start low, go slow’ to gain patient confidence and reduce the risk of hypoglycaemia.44
Select one of two insulin schedules:
- basal insulin (eg glargine U100 or U300) once daily, irrespective of meals
- co-formulated insulin (eg degludec–aspart) or premixed (biphasic) insulin (eg lispro–lispro protamine or aspart–protamine insulin) once daily before the largest carbohydrate-containing meal of the day. Premixed insulins have various combinations of intermediate-acting basal insulins and rapid-acting insulins. Common combinations are 25/75, 30/70 and 50/50 (rapid-acting/basal insulins), by percentage.
Basal insulin alone has a slightly lower risk of hypoglycaemia, especially if the fasting glucose is consistently above target.31,45
Premixed or co-formulated insulin may be more appropriate and simpler for a patient where fasting and postprandial glucose are both consistently elevated.
Dosage adjustment can be more complex with premixed and co-formulated insulins, as both insulin components are adjusted simultaneously, possibly increasing the risk of hypoglycaemia and weight gain compared with basal insulin.45,46
Non-insulin glucose-lowering medicines should generally be continued, as:
- cessation of non-insulin glucose-lowering medicines before blood glucose targets are achieved may result in significant hyperglycaemia44
- ongoing use can mitigate weight gain (particularly SGLT2i and GLP-1 RAs)31
- ongoing use may be insulin-sparing and can reduce the risk of hypoglycaemia as well as hyperglycaemia.44
Careful review of use of sulfonylureas should be considered if risks of hypoglycaemia are present (commencing insulin in older people, or up-titration of insulins containing prandial/rapid-acting insulins).
A low starting dose for premixed, co-formulated or basal insulins of 10 units or 0.1–0.2 units/kg in the evening will usually be a safe dose; however, titration is needed, as this low dose will be insufficient for achieving glycaemic targets in most people.
Appendix 2. Guide to insulin initiation and titration
provides detailed information about insulin doses, titration and intensification.