Initiating insulin for people with type 2 diabetes

Insulin depletion is probable over time

Type 2 diabetes is a progressive disease characterised by insulin resistance and a decreasing ability of pancreatic β-cells to produce insulin. Both of these factors contribute to hyperglycaemia. Alongside lifestyle modifications, most patients with diabetes begin treatment with metformin (with or without other glucose-lowering medicines). However, due to the progressive nature of type 2 diabetes, treatment with insulin is eventually required in some patients.

Making the decision to initiate insulin

New Zealand guidelines recommend that insulin treatment be considered for any person with type 2 diabetes who has not met their HbA_1c target despite optimal lifestyle modification and pharmacological management with non-insulin glucose-lowering medicines.¹ Insulin initiation is recommended for all patients with significant hyperglycaemia (e.g. HbA_1c > 80 – 90 mmol/mol)^* at any stage, including diagnosis.¹

^* This is higher than previously recommended (75 mmol/mol) due to the availability of more options to manage hyperglycaemia²

Reinforce the importance of lifestyle interventions

Emphasise to all patients initiating insulin that this is not a substitute for a healthy lifestyle and that behavioural strategies such as exercise, healthy eating and smoking cessation should still continue. Alcohol consumption should be limited as this increases the risk of hypoglycaemia in patients taking insulin.

It may be possible for some people with type 2 diabetes, following significant weight loss, to stop taking insulin, especially if they have had diabetes for a short period, now have a body mass index (BMI) < 30 kg/m² and are close to or at their HbA_1c target.

For further information on weight management, see: Weight loss: the options and the evidence

When to seek further advice

Advice about an insulin regimen should be sought from a diabetes clinic in cases where:³

• The patient is a child or adolescent
• The patient is very lean or has lost weight rapidly – testing for glutamic acid decarboxylase (GAD) autoantibodies indicating type 1 diabetes may be appropriate
• There is repeated hypoglycaemia
• The patient is a vocational driver
• HbA_1c levels remain above target following insulin initiation and titration – the HbA_1c target should ideally be reached within three to six months of treatment initiation and optimisation⁴

Choosing an insulin regimen

There are three main types of insulin regimens used by people with type 2 diabetes: basal, basal-bolus and biphasic (see: Funded insulins available in New Zealand). Selection of a regimen should be guided by the pattern of blood glucose results and individual patient factors (also see: “Treatment intensification: basal-bolus or biphasic?”). Typically, people with type 2 diabetes are initiated on basal insulin.

For a schematic representation comparing the duration of different insulins, see: www.nzf.org.nz/nzf_3629

Basal regimens use an intermediate/long-acting insulin (basal insulin) injected once or twice daily. Basal insulin reduces HbA_1c by controlling hepatic glucose production. There are two types of basal insulin available fully funded in New Zealand (see: “Funded insulins available in New Zealand” for brand names and product variations):

• Isophane insulin (e.g. Humulin NPH or Protaphane), also known as NPH^* insulin, is an intermediate-acting insulin – suitable for most patients
• Insulin glargine (e.g. Lantus), an insulin analogue, is a long-acting insulin – consider switching to this insulin if patients have significant hypoglycaemia with isophane insulin⁵

^*Neutral Protamine Hagedorn (NPH)

Basal-bolus regimens use a rapid/short-acting (bolus) insulin injected before or with meals and snacks and an intermediate/long-acting (basal) insulin injected once or twice daily. Rapid/short-acting formulations reduce HbA_1c by decreasing post-prandial glucose levels. Basal-bolus insulin regimens are usually administered as a flexible dose (i.e. carbohydrate counting to match insulin requirements to the carbohydrate content of the upcoming meal) but some patients may use a fixed dose, depending on their circumstances, e.g. if they are unable to count carbohydrates.

For information on carbohydrate counting, see: bpac.org.nz/2019/diabetes-insulin.aspx

Biphasic regimens use an intermediate-acting insulin mixed with a short-acting insulin, injected twice daily, i.e. before breakfast and dinner. Biphasic regimens are an alternative to basal-bolus regimens for patients who are taking basal insulin and require treatment intensification. A variety of pre-mixed biphasic insulins with differing proportions of intermediate-acting and short-acting insulin are funded (See Table 2 in Funded insulins available in New Zealand). A reasonable initial choice is a biphasic insulin containing a rapid-acting insulin analogue, e.g. Humalog Mix25 (biphasic insulin lispro) or Novomix30 (insulin aspart), because of the faster onset of action than those containing human neutral insulin, allowing patients to “inject and eat”. Humalog Mix50 may be helpful if the premixed insulin is administered with a large carbohydrate-based meal, particularly if the patient has postprandial hyperglycaemia with mixes containing 25% or 30% rapid/short-acting insulin.¹

Patients using insulin should begin self-monitoring of blood glucose

Self-monitoring of blood glucose is recommended to help guide insulin dosing and meal planning. For patients with type 2 diabetes initiating basal insulin, a once daily measurement is usually sufficient, taken either:

• Before breakfast (fasting) if initiating insulin injections in the evening; OR
• Prior to evening dinner if initiating insulin injections in the morning

The aim of treatment is to achieve blood glucose levels between 6 – 8 mmol/L at these times.³

For some patients self-monitoring of blood glucose levels may be useful before initiating insulin to determine their daily pattern of glycaemia, e.g. before and after main meals for three days prior to initiation.

Various blood glucose meters are available fully funded

There are three blood glucose testing meters currently fully funded^* for people with type 2 diabetes who are taking insulin:^{6, 7}

• CareSens N – big screen and large numbers
• CareSens N Pop – small, slim meter; backlit for testing in low light environments
• CareSens N Premier – big screen and large numbers; bluetooth functionality

These meters all use the CareSens N blood glucose test strips. Patients should be encouraged to keep a record of their blood glucose measurements, as well as noting any changes to their normal diet, routine or health. Logbooks are available from diabetes clinics or diabetes medicine manufacturers. All funded blood glucose meters can be read by the SmartLog software supplied by the manufacturer at no cost to the patient. Patients should bring their meter and logbook to their appointments. A variety of smartphone apps are also available to record data.

^*The CareSens-Dual meter measures blood glucose and blood ketones (using the CareSens PRO and KetoSens test strips); this meter is not funded for people with type 2 diabetes

N.B. Although mainly used by people with type 1 diabetes, continuous blood glucose monitoring may be useful in some people with type 2 diabetes taking insulin.⁸ For further information on continuous blood glucose monitoring, see: bpac.org.nz/2019/diabetes-insulin.aspx

Patient information on diabetes smartphone apps is available from: www.healthnavigator.org.nz/apps/d/diabetes-apps/

Recommended initial isophane treatment regimen

New Zealand guidelines recommend starting with once daily basal insulin, administered in the evening to help reduce high blood glucose levels in the morning.¹ However, administering the injection in the morning may be appropriate for some patients who have increases in blood glucose levels throughout the day (Table 3).

Table 3. Patient characteristics to guide once daily dosing of basal insulin⁹

A weight-based approach is recommended to determine the initial basal insulin dose:¹

• 0.1 units/kg daily if any of:
  • HbA_1c < 64 mmol/mol
  • BMI < 18 kg/m² (less likely to have type 2 diabetes)
  • Older (e.g. aged > 65 years) or frailty
  • Renal or liver failure
• 0.2 units/kg daily if HbA_1c > 64 mmol/mol and BMI > 18 kg/m²

Patients will need to titrate the insulin dose upwards from this starting point based on their fasting blood glucose levels. Having patients adjust their own doses, rather than waiting for instructions from a clinician, is usually a more successful approach for achieving HbA_1c targets.¹⁰

There are different methods for titration; New Zealand guidelines recommend increasing the dose by 10% or 2 units if patients have three consecutive days of fasting blood glucose levels > 7 mmol/L (i.e. the dose can be increased every three days).¹

The upwards titration of basal insulin should be stopped if:¹

• Hypoglycaemia occurs (blood glucose levels < 4 mmol/L); OR
• Fasting blood glucose levels are < 7 mmol/L; OR
• Dose > 0.5 units/kg/day – consider adding a rapid/short-acting insulin (usually one dose with the largest meal)

If fasting blood glucose levels < 6 mmol/L are recorded, insulin doses should be reduced:³

• Between 4 – 6 mmol/L: decrease insulin dose by 2 units
• < 4 mmol/L: decrease insulin dose by 4 units

Treatment intensification: basal-bolus or biphasic?

Treatment intensification should be considered for patients who have not reached their HbA_1c target after three months’ treatment with basal insulin, despite achieving fasting blood glucose levels < 7 mmol/L and/or taking a dose of 0.5 units/kg/day.¹ The choice of intensification to a basal-bolus or biphasic regimen should be based on patient characteristics and preference (Table 4).

Table 4. Factors influencing the choice between a basal-bolus and biphasic regimen¹

A treatment algorithm from the NZSSD type 2 diabetes management guideline (2021) is available from: t2dm.nzssd.org.nz/Insulin-Algorithm.html

Initiating a basal-bolus regimen

When adding bolus insulin to a basal regimen, start with a rapid-acting insulin immediately before the largest meal (also known as a “basal plus” regimen):¹

• Start with 4 units or 10% of the basal dose (maximum starting dose is 10 units)
• Stop sulfonylurea once established on bolus insulin
• Continue lifestyle management and other glucose-lowering medicines
• Monitor blood glucose levels before and two hours after that meal
• Basal insulin dose may need to be reduced to prevent hypoglycaemia, particularly if HbA_1c levels < 64 mmol/mol

Increase the dose of rapid-acting insulin by 2 units if blood glucose level increase with the meal is > 3 mmol/L on three occasions. Adherence and injection technique should be checked before increasing doses.

Add bolus insulin at other meals if HbA_1c remains above the target or blood glucose levels increase by > 3 mmol/L at other meals. N.B. The doses of bolus insulin are likely to be different at different meals.

Add correction doses of rapid-acting insulin to treat pre-meal hyperglycaemia. The calculation is: 1 unit for every x mmol over 8 mmol/L, based on the total daily dose of basal + bolus insulin (see: Table 5 and "Example of how to calculate a correction dose of insulin"). Initially it may be safer to limit the correction dose to a maximum of 6 – 10 units. Other correction doses may be added, e.g. before bed, but there should be at least three hours before correction doses.¹

Table 5. Correction insulin dose calculation based on total daily insulin dose¹

Initiating a biphasic regimen

Emphasise to patients the importance of premixing insulin by gently inverting the device before each use to reduce the risk of hypoglycaemia.

The type of biphasic regimen depends on whether the patient predominantly has one large meal per day or multiple meals per day (Table 7). Adherence and injection technique should be checked before any dose increases.

If after three months of optimised treatment HbA_1c levels remain above the target, consider:¹

• Switching one or both injections to Humalog Mix50 if significant hyperglycaemia after meals
• Adding bolus insulin at other meals if blood glucose levels increase > 3 mmol/L at these times (e.g. lunch, large snacks)
• Switching to a basal-bolus regimen

Table 7. Guide for initiating biphasic insulin in people with type 2 diabetes¹

Predominately one large meal per day

Multiple meals per day

Start once daily premixed insulin: Convert the daily dose of basal insulin to premixed insulin Administer before the largest meal Monitor blood glucose levels before and two hours after that meal Increase dose by 10% if blood glucose level increase with that meal is > 3 mmol/L and fasting blood glucose level is > 10 mmol/L

Start twice daily premixed insulin: Convert the daily of dose basal insulin to premixed insulin Administer half the dose before breakfast and the other half before dinner; consider a different ratio if there is a large difference in meal sizes or the patient is older, e.g. 2/3 of the total daily insulin dose before the larger meal and 1/3 before the smaller meal; older people should have lower evening doses Monitor blood glucose levels before and two hours after that meal If on three occasions blood glucose levels increase > 3 mmol/L with breakfast and pre-dinner blood glucose levels are > 10 mmol/L, increase the breakfast dose by 10% If on three occasions blood glucose levels increase > 3 mmol/L with dinner and pre-breakfast blood glucose levels are > 10 mmol/L, increase the dinner dose by 10%

Education is key for patients initiating insulin

Ongoing advice and education are paramount to ensure patients are confident with their prescribed insulin regimen.

An initial session for patients starting insulin should cover:^{1, 3, 4}

• Self-monitoring of blood glucose levels
• How to use their injection device, injection technique and rotation of injection sites
• Appropriate storage of insulin and disposal of injection devices and needles
• How to titrate the insulin dose based on self-measurement of blood glucose levels
• What to do during disruptions to their typical daily routine, such as if they are acutely unwell, miss meals or are travelling
• Managing hypoglycaemia (see: "Managing hypoglycaemia"), including how diet and exercise can affect the risk, recognising symptoms, testing blood glucose levels during suspected hypoglycaemia and how to respond if levels are too low
• Driving safely while using insulin and any impact using insulin may have on their fitness to drive (see: t2dm.nzssd.org.nz/Section-100-Diabetes-and-driving)
• Use of a Medic Alert bracelet

The initial session will likely require a longer consultation time and/or a team approach with the general practitioner, nurse practitioner or practice nurse; consider referral to a diabetes nurse specialist or education programme covering the above points if offered by the local DHB or PHO.

After the initiation of insulin, make regular contact with the patient, e.g. phone calls from the practice nurse with in-person or virtual consultations, as required, until satisfactory glycaemic control is achieved.

Further resources

Diabetes group education classes are offered by local Diabetes Centres. Diabetes New Zealand provides additional information on subjects such as healthy eating and exercise as well as providing links to support groups and research publications.

Pamphlets for patients can be downloaded or ordered from: https://www.diabetes.org.nz/pamphlet-ordering

The Diabetes New Zealand “Take Control Toolkit” for patients is available at no cost as a smartphone app: https://www.diabetes.org.nz/take-control-toolkit-1