Insulin Glargine

Insulin glargine is a synthetic version of insulin used to treat both type 1 and type 2 diabetes mellitus. Its structure has been modified to lengthen its effectiveness and allow once-daily dosing. It is a relatively new addition to the list of commercially-available insulins, having been approved in April 2000, and joins other types of insulin including Humulin (regular human insulin, rDNA origin, from Eli Lilly) and Humalog (insulin lispro, from Eli Lilly). It is made and marketed as Lantus by Sanofi-Aventis.

Uses

Insulin glargine is specifically indicated for the treatment of adults and children with type 1 diabetes mellitus and adults with type 2 diabetes mellitus who require long-acting insulin for the control of hyperglycemia.

How Insulin Glargine is Taken

Like most other insulin formulations, insulin glargine is available in 10-mL vials at a 100 Unit/mL concentration (U-100). The drug is injected subcutaneously (SC) once a day at the same time day after day. It can be taken in the mornings or evenings, but the incidence of nocturnal low blood sugar episodes is lower with morning administration. Since insulin glargine depends on gradual formation of crystals that precipitate in the subcutaneous tissue, it is important to avoid injecting into muscle; a case report demonstrates that intramuscular injection may result in accelerated activity and thus cause hypoglycemia. ^[1]

Since the glucose-lowering effects of insulin glargine take time to develop, it is often prescribed as part of a more complex insulin regimen that includes shots of a faster-acting insulin before meals. Separate shots are required, since insulin glargine cannot be mixed with a faster-acting insulin in the same syringe. Insulin glargine can also be part of a regimen that includes oral antidiabetic medications.

How Insulin Glargine Works

The primary objective of all insulin regimens is to regulate glucose metabolism in order to lower blood glucose concentrations. Insulin lowers blood glucose levels by stimulating cells to uptake glucose from the bloodstream and by inhibiting new glucose production by the liver.

How the Body Affects Insulin Glargine

Insulin glargine is metabolized to form two active metabolites (called M1 and M2) which display activity similar to that of their insulin parent.

Side Effects

The most common side effects associated with the use of insulin glargine are:

• allergic reactions
• injection site reaction
• lipodystrophy (abnormalities in fat tissue from injection)
• pruritus (itching)
• rash
• hypoglycemia (low blood sugar levels)

Risks and Precautions

In diabetics treated with insulins, the ability to concentrate and/or react may be impaired as a result of changing blood sugar levels. Low blood sugar episodes usually result in more symptoms and resolve more quickly than episodes of high blood sugar.

The kinetics of insulin glargine can vary greatly from person to person, and from day to day in a given person. Insulin absorption may also be altered by injection site and depth, exercise of the limb or region into which the insulin has been injected, and ambient temperature.

Video: FDA is investigating the possibility that Lantus (insulin glargine) may be associated with an increased risk of cancer. Three of four observational studies published recently in the journal Diabetologia suggested an increased cancer risk associated with Lantus. All of the studies had drawbacks or inconsistencies that preclude drawing any firm conclusions about whether the drug is actually associated with an increased risk of cancer.

Drug Interactions

These drugs may increase the blood-glucose-lowering effect of insulin glargine:

• oral antidiabetes products
• ACE inhibitors
• disopyramide
• fibrates
• fluoxetine
• MAO inhibitors
• propoxyphene
• salicylates
• somatostatin analog (e.g., octreotide)
• sulfonamide antibiotics.

These drugs may reduce the blood-glucose-lowering effect of insulin glargine:

• corticosteroids
• danazol
• diuretics
• sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline)
• isoniazid
• phenothiazine derivatives
• somatropin
• thyroid hormones
• estrogens
• progestogens (e.g., in oral contraceptives)
• protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine)
• beta-blockers
• clonidine
• lithium salts
• pentamidine
• guanethidine
• reserpine
• alcohol

Effectiveness

Insulin glargine was engineered to take effect more slowly and to last longer in the body than other forms of insulin. It differs from the natural form of the hormone because of the addition of two positive charges (two arginine molecules) to the C terminus of the B chain; the second difference is the replacement of an asparagine residue at position 21 in the A chain. The end result is a more consistent release of insulin into the circulation, with no pronounced peaks over 24 hours. Insulin glargine has an activity profile that is more stable and longer-acting, with less nighttime variability than NPH and Ultralente insulins.

Insulin glargine was found to be effective in improving blood sugar control in a large, diverse population with longstanding type 2 diabetes.^[2]

Alternatives

Insulin detemir is another form of extremely long-acting insulin that relies on binding to serum albumin to extend its activity in the body.

References

1. ↑ Karges B, Boehm BO, Karges W. Early hypoglycaemia after accidental intramuscular injection of insulin glargine. Diabet Med. 2005 Oct;22(10):1444-5. Abstract
2. ↑ Davies M, Storms F, Shutler S, Bianchi-Biscay M, Gomis R; ATLANTUS Study Group. Improvement of glycemic control in subjects with poorly controlled type 2 diabetes: comparison of two treatment algorithms using insulin glargine. Diabetes Care. 2005 Jun;28(6):1282-8. Abstract Full Text PDF