Insulin glargine is a manmade version of human insulin that is FDA approved for the treatment of adults and children with type 1 diabetes and adults with type 2 diabetes to improve and maintain glycemic control. Insulin glargine is a long-acting insulin that is injected once daily and provides a basal level of insulin throughout the day. Regimens often combined it with rapid-acting insulin to obtain optimal glycemic control. The insulin should not be used for the treatment of diabetic ketoacidosis, as short-acting insulin is preferred. 

In type 1 diabetes, both long-acting and short-acting insulins are often necessary at the onset of the disease. In type 1 diabetes, the body lacks the ability to produce insulin from the pancreas due to autoimmune-mediated beta cell destruction, and thus there is a rapid loss of regulation of blood glucose levels. Insulin glargine functions as basal glycemic control due to its 24-hour duration of action, while rapid-acting insulin works as coverage of elevated blood glucose and carbohydrate intake due to its quick onset and short duration of action. 

In adults with type 2 diabetes, insulin glargine, or another long-acting insulin, should be initiated for glycemic control after 2 or 3 oral antidiabetic medications have failed to attain glycemic control or in patients with a hemoglobin A1c value higher than 9% who are experiencing symptoms. Insulin glargine may be used alone in individual patients, or it could be used along with rapid-acting insulin and/or oral medication(s) for diabetes management. Insulin glargine does not have approval for children with type 2 diabetes.[1]  

Insulin glargine is not FDA approved in pregnancy, although studies have not shown contraindications to its use or adverse fetal outcomes. It is considered a first-line treatment for gestational diabetes after lifestyle modifications have proven insufficient.[2][3]

Insulin glargine is a recombinant analog of human insulin that binds to insulin receptors (IR). Insulin is necessary for the regulation of lipid, glucose, and energy homeostasis. It acts mainly on the skeletal muscle, adipose tissue, and liver. The IR is a tyrosine kinase receptor that has two extracellular alpha domains and two intracellular catalytic beta domains. Upon insulin binding, a conformational change occurs to the beta catalytic domains that then activate the tyrosine kinase domains, causing them to auto-phosphorylate the beta subunits. Once activated, the beta subunits can bind docking proteins, which leads to the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3k) and an intracellular signaling cascade, eventually activating protein kinase B (also known as Akt). Akt regulates the activity of the glucose transporter type 4 (GLUT4) receptor, protein kinase C (PKC), and the mitogen-activated protein kinase (MAPK or MAP kinase) pathway.[4]

Insulin glargine has an onset of action of 1.5 to 2 hours. It has a long duration of action up to 24 hours due to modifications of amino acids, including Asn to Gly at position 21 of the A chain and the addition of two Arg residues and positions 31 and 32 of the B chain. This arrangement allows the insulin to remain soluble at a pH of 4.0, which is the pH of the solution in which it is administered, and then become insoluble at physiologic pH. Once insulin glargine is injected into the body and introduced to the higher pH, the insoluble precipitate that forms slowly releases soluble protein over 24 hours.[5]

Insulin glargine comes either in 100 ml vials or in dosing pens that contain 3 ml cartridges of medication and is administered via subcutaneous injection only. The drug is available at a concentration of 100 units per ml. Its administration includes a diluent that has a pH of 4.0 to maintain the solubility of the drug before use. The medication is administered once daily at the same time of day by the patient. Decisions of when to administer insulin glargine are dependent on the schedule of the patient as well as the resultant effects that the insulin has on the particular patient's blood glucose levels. Patients should rotate injection sites to avoid lipodystrophy; these include the top of the thighs, back of the upper arms, buttocks, or abdomen. 

The estimated starting dose of insulin therapy is usually 0.4 to 0.5 units/kg per day of total insulin. However, differing amounts might be necessary for patients undergoing puberty or those with obesity. The current consensus regarding the dosing of basal insulin is that it should make up 50% of the total daily insulin requirement. Although it is worth noting that recent studies have suggested that a basal dose closer to 40% of total daily insulin may result in more optimal glycemic control.[6]

The most common adverse effect of insulin glargine is hypoglycemia. Special attention is necessary for insulin usage in patients who are fasting, recently changed their diet, or have had recent activity changes such as beginning a workout program. Hypoglycemia characteristically demonstrates autonomic symptoms, including diaphoresis, nausea, palpitations, tremors, anxiety, lethargy, and decreased concentration, among others. With severe hypoglycemia, unconsciousness, seizures, coma, and death may occur. Adverse effects may also include allergic reactions to the diluent, site injection reactions or infection, and lipodystrophy at the injection site. Insulin glargine may also cause pain upon injection at the site due to the acidity of the diluent.[7]

It is also essential to be aware of medications that are administered concurrently with insulin glargine. Certain medications can increase the risk of hypoglycemia when given with insulin. Certain medications may also diminish the effectiveness of insulin glargine, causing hyperglycemia, or mask symptoms of hypoglycemia. The risk of hypoglycemia may increase with coadministration of antidiabetic drugs, other insulins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs, sulfonamide antibiotics, and somatostatin analogs. The effectiveness of insulin glargine may become diminished when administered along with atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, isoniazid, niacin, phenothiazines, protease inhibitors, somatotropin, sympathomimetic agents and thyroid hormone replacements. Another concern regarding drug interactions includes the possibility of medications such as beta-blockers, clonidine, guanethidine, and reserpine masking symptoms of hypoglycemia. Lastly, thiazolidinediones have an increased risk of causing dose-related fluid retention when administered with insulin.

Insulin glargine is contraindicated in patients with a documented hypersensitivity to the drug or one of its components. It also should not be administered during a hypoglycemic episode. However, patients can restart the medication once the episode has resolved. Caution is advisable in scenarios including current infection, hypokalemia, kidney dysfunction, and liver disease. Insulin glargine is considered safe during pregnancy, and there are no known risks of infant harm if using the medication during lactation. However, the FDA lists insulin glargine as category C in pregnancy, stating that the patient should only use it if the benefits outweigh the risk.[2]