Insulin glargine (Lantus) for type 1 and 2 diabetes mellitus

• Insulin glargine is a long-acting insulin analogue that can be used in type 1 and 2 diabetes mellitus.
• Insulin glargine has similar efficacy to that of isophane insulin in controlling blood glucose.
• Insulin glargine can reduce the overall incidence of hypoglycaemia, mostly at night, compared with isophane insulin. The risk of severe hypoglycaemia is similar to that with isophane insulin.
• Inform patients that insulin glargine is a clear, not a cloudy, solution. It should not be confused with clear short- or rapid-acting insulins.
• Insulin glargine can be given once daily, which may be more convenient for patients or carers who need to inject intermediate-acting insulin more than once daily.
• If switching from twice-daily isophane insulin to insulin glargine, use an initial dose that is 20% less than the total previous dose of isophane insulin, and titrate upwards if needed.

Insulin glargine is listed on the Pharmaceutical Benefits Scheme (PBS) as an unrestricted benefit. Insulin glargine can be prescribed on the PBS for adults and children with type 1 diabetes mellitus and adults with type 2 diabetes mellitus who require insulin.

Insulin glargine was listed on a cost-effectiveness basis compared with isophane insulin.¹ The Pharmaceutical Benefits Advisory Committee accepted that the improvement in hypoglycaemic event rates with insulin glargine, albeit in a population which cannot be defined, was cost effective at the price proposed.^1,2

Insulin glargine was generally as well tolerated as isophane insulin in studies. As with other insulins, adverse effects include hypoglycaemia, injection-site reactions, weight gain, headache, diarrhoea and infections.^{3,8–10,12–17,21–24} Insulin glargine may cause more pain at the injection site than isophane insulin (up to 6% and 1% of patients, respectively).^3,4,9,13,21 Injection-site reactions were generally mild and did not result in cessation of treatment.

Report suspected adverse reactions to the Adverse Drug Reactions Advisory Committee (ADRAC) online or by using the 'Blue Card' distributed with Australian Prescriber. For information about reporting adverse reactions, see the Therapeutic Goods Administration website.

Insulin glargine reduces, but does not eliminate, the risk of hypoglycaemia

As can be seen in Table 1, hypoglycaemia:

• remains a risk with insulin glargine
• is more common in type 1 than type 2 diabetes
• is slightly less frequent with insulin glargine compared with isophane insulin
• occurs at a similar rate between these insulins for severe events.

Table 1.
Proportion of patients with at least one hypoglycaemic event in studies of insulin glargine compared with isophane insulin^{8–18,21–23}

* Definitions of hypoglycaemic events varied between studies: symptomatic (clinical symptoms confirmed or unconfirmed by FBG < 2.0–4.2 mmol/L), nocturnal (symptomatic hypoglycaemia occurring during sleep between bedtime and getting up in the morning, i.e. before morning pre-breakfast FBG measurement and morning insulin injection), severe (symptomatic hypoglycaemia requiring assistance from another person, with either FBG < 2.0–3.1 mmol/L or prompt recovery after administration of oral carbohydrate, intravenous glucose or glucagon).

Insulin glargine mainly reduces the incidence of hypoglycaemia at night.^9,15–19 Studies of up to 1 year found that insulin glargine reduced the proportion of patients with at least one episode of nocturnal hypoglycaemia by 5–20% compared with isophane insulin.^8–15 In patients with type 1 diabetes, absolute rates of nocturnal hypoglycaemia were reported as 1–2 episodes per month with insulin glargine and 3–4 episodes per month with isophane insulin.^18,19 The absolute rates for patients with type 2 diabetes were 4–5 episodes per year with insulin glargine and 7–8 episodes per year with isophane insulin.^16,17

Lower incidence of hypoglycaemia is more apparent with insulin glargine compared with once-daily isophane insulin

The incidence of hypoglycaemia appears lowest when insulin glargine is compared with isophane insulin once daily^10,20,23,24; this is likely due to once-daily doses being higher than individual doses of isophane insulin twice daily. In one 4-week study of type 1 diabetes¹⁰, the proportion of patients with at least one episode of nocturnal hypoglycaemia was 36% with insulin glargine, 44% with isophane insulin twice daily, and 66% with isophane insulin once daily. In a 28-week study of type 2 diabetes^13,24, there was less symptomatic hypoglycaemia with insulin glargine but only when compared with the subgroup of patients given isophane insulin once daily (46% versus 60%, respectively).

Insulin glargine was generally as well tolerated as isophane insulin in studies. As with other insulins, adverse effects include hypoglycaemia, injection-site reactions, weight gain, headache, diarrhoea and infections.^{3,8–10,12–17,21–24} Insulin glargine may cause more pain at the injection site than isophane insulin (up to 6% and 1% of patients, respectively).^3,4,9,13,21 Injection-site reactions were generally mild and did not result in cessation of treatment.

Report suspected adverse reactions to the Adverse Drug Reactions Advisory Committee (ADRAC) online or by using the 'Blue Card' distributed with Australian Prescriber. For information about reporting adverse reactions, see the Therapeutic Goods Administration website.

Insulin glargine reduces, but does not eliminate, the risk of hypoglycaemia

As can be seen in Table 1, hypoglycaemia:

• remains a risk with insulin glargine
• is more common in type 1 than type 2 diabetes
• is slightly less frequent with insulin glargine compared with isophane insulin
• occurs at a similar rate between these insulins for severe events.

Table 1.
Proportion of patients with at least one hypoglycaemic event in studies of insulin glargine compared with isophane insulin^{8–18,21–23}

* Definitions of hypoglycaemic events varied between studies: symptomatic (clinical symptoms confirmed or unconfirmed by FBG < 2.0–4.2 mmol/L), nocturnal (symptomatic hypoglycaemia occurring during sleep between bedtime and getting up in the morning, i.e. before morning pre-breakfast FBG measurement and morning insulin injection), severe (symptomatic hypoglycaemia requiring assistance from another person, with either FBG < 2.0–3.1 mmol/L or prompt recovery after administration of oral carbohydrate, intravenous glucose or glucagon).

Insulin glargine mainly reduces the incidence of hypoglycaemia at night.^9,15–19 Studies of up to 1 year found that insulin glargine reduced the proportion of patients with at least one episode of nocturnal hypoglycaemia by 5–20% compared with isophane insulin.^8–15 In patients with type 1 diabetes, absolute rates of nocturnal hypoglycaemia were reported as 1–2 episodes per month with insulin glargine and 3–4 episodes per month with isophane insulin.^18,19 The absolute rates for patients with type 2 diabetes were 4–5 episodes per year with insulin glargine and 7–8 episodes per year with isophane insulin.^16,17

Lower incidence of hypoglycaemia is more apparent with insulin glargine compared with once-daily isophane insulin

The incidence of hypoglycaemia appears lowest when insulin glargine is compared with isophane insulin once daily^10,20,23,24; this is likely due to once-daily doses being higher than individual doses of isophane insulin twice daily. In one 4-week study of type 1 diabetes¹⁰, the proportion of patients with at least one episode of nocturnal hypoglycaemia was 36% with insulin glargine, 44% with isophane insulin twice daily, and 66% with isophane insulin once daily. In a 28-week study of type 2 diabetes^13,24, there was less symptomatic hypoglycaemia with insulin glargine but only when compared with the subgroup of patients given isophane insulin once daily (46% versus 60%, respectively).

Insulin glargine is usually injected subcutaneously once daily at bedtime.³ The initial dose and time of administration is determined on an individual basis and adjusted according to blood glucose levels.³

Switching from other insulins to insulin glargine

When changing treatment from another intermediate- or long-acting insulin to insulin glargine, the dose of rapid- or short-acting insulin, or oral hypoglycaemic agents, may need adjustment.³

Patients who previously used once-daily isophane insulin can generally be switched to insulin glargine using the same dose. However, some patients who used twice-daily isophane insulin reported increased hypoglycaemia during dose titration with insulin glargine.^21–23 If switching such patients to insulin glargine, use an initial dose that is 20% less than the total previous dose of twice-daily isophane insulin, and titrate upwards if needed.³

Inform patients and/or carers that insulin glargine:

• is a long-acting insulin for lowering blood glucose levels between meals
• is a clear solution — not to be confused with rapid- and short-acting insulins, which are also clear solutions
• is usually given as a once-daily injection
• must not be mixed with any other insulin or be diluted
• can lower the risk of, but not prevent, episodes of hypoglycaemia
• has a prolonged effect, which may delay recovery from hypoglycaemia.³

Advise about the factors that increase the risk of hypoglycaemia with insulins, including:

• inappropriate use of high doses
• missing or delaying meals
• insufficient carbohydrate intake
• drinking alcohol
• unaccustomed or unplanned exercise.^4,6

Suggest or provide the Lantus Consumer Medicine Information (CMI) leaflet.