Insulin glargine

Insulin glargine is a biosynthetically produced human insulin (Kasper 2015). It is one of the insulin analogues and was the first long-acting insulin analogue (Heinemann 2000).

Pharmacodynamics

In insulin glargine, asparagine at amino acid 21 was replaced by glycine. In addition, two arginine residues were added at position B 30, the C- terminus of the B-chain (Kasper 2015).

These changes result in a shift of the isoelectric point toward a neutral pH. As a result, the insulin molecule is less soluble at the injection site and can be deposited in the subcutaneous tissue to form a depot from which insulin is slowly released (Philips 2006).

Indication

Insulin glargine may be used in:

• Type 1 diabetics as basal insulin in the context of intensified conventional insulin therapy (ICT)
• Type 2 diabetics as supportive basal insulin in the context of basal-assisted oral therapy (BOT) (Fridrich 2021).
• Renal insufficiency

In a study by Prof. Alice Cheng, Toronto, it was shown that with insulin glargine 300 E / ml compared to insulin degludec (see insulin analogues) a 0.43 percentage point greater reduction in HbA1c- value could be achieved in renal impairment with an eGFR of < 60 ml / min / 1.73 m². The risk of hypoglycemiawas comparable.

The glycemic control values of patients with an eGFR of ≥ 90 ml / min / 1.73 m² were comparable under both treatment options (Walter 2020).

Dosage and route of administration

Insulin glargine can be injected s. c. or intracutaneously. However, it must not be given i. v., as are all other long-acting insulins (Herold 2022). Glargine, like all other delay insulins, is not suitable for insulin pump therapy (Dellas 2018).

Glargine U 100 is injected 1 or 2 x / d, glargine U 300 1 x / d, the time of day of the injection is flexible (Haak 2018).

In type 2 diabetics, glargine is usually started with an evening dose such as 5 - 15 IU or weight-adjusted with 0.2 IU / kg bw (Kasper 2015). Further adjustment of the dose see insulin.

Advantages

• Hypoglycemia:

Compared to NPH- ins ulin, insulin glargine leads less frequently to hypoglycemia, especially less frequently to nocturnal hypoglycemia (Kasper 2015).

In three randomized, controlled, open-label phase 3 studies, glargine U 300 showed fewer hypoglycemias in type 1 diabetics than glargine U- 100: 6.2% vs. 9.3%. Similarly, the rate of severe hypoglycemia was also numerically lower: 0.23 events/patient-year vs. 0.29 events/patient-year (Danne 2021).

• HbA1c- value:

In the BRIGHT- study, glargine U- 100 and glargine U- 300 showed comparable reductions in HbA1c- levels in insulin naïve elderly type 2 diabetics.

In the group of ≥ 70-year-olds, glargine U- 300 showed a better effect than glargine U- 100 in terms of HbA1c- reduction - without increasing the risk of hypoglycemia: -1.69 % vs. -1.34 % (Müller- Wieland 2021).

• Carcinoma risk:

According to recent evidence, glargine use is not associated with an increased risk of cancer (Kasper 2015).

Adverse effects

• Hypoglycemia
• Local inflammation at the injection site
• Lipohypertrophy
• Lipoatrophy
• allergic reaction of immediate type
• edema
• myalgia
• retinopathy
• visual disturbances
• taste disturbances (Fridrich 2021)

Contraindication

Absolute contraindications:

- Hypoglycemia

- Insulinoma (Flake 2021)

Preparations

• Insulin Glargine U 100:

Trade name Lantus (Herold 2022), which was first approved in 2001 (Heinemann 2000). The onset of action occurs after 1 h, and the duration of action is 20 - 27 h (Haak 2018). The maximum effect level is reached only after 3 - 4 days at constant dosage (Weihrauch 2020).

• Biosimilar Abasaglar (Alawi 2019), which received approval in 2015 (Schmeisl 2019). It is comparable to Lantus in terms of efficacy, hypoglycemic risk, immunogenicity, and tolerability, but the costs incurred are lower (Lamb 2018).

• Insulin Glargine U 300:

Trade name Toujeo (Danne 2016). Toujeo has been on the market since 2015 (Danne 2016). Here, the effect occurs after 1 - 6 h, the duration of action is > 30 - 32 h (Haak 2018).

Like insulin detemir, glargine has a plateau-like effect (Kasper 2015).

It does not need to be swished before an injection (Herold 2022). Insulin glargine should not be mixed with other insulins (Kasper 2015).

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