Insulin Glargine

Insulin Glargine Brand Names

BASAGLAR | Lantus | Lantus SoloStar | Toujeo Max SoloStar | Toujeo SoloStar

What is Insulin Glargine

Insulin glargine is a long-acting basal insulin analog that is produced from a chemical modification of regular human insulin; the amino acid asparagine is replaced by glycine at position A21, and 2 arginines are added to the C-terminus of the B chain. Because of these changes, insulin glargine is soluble in an acidic environment; insulin glargine forms a stable hexamer precipitate in the neutral pH environment upon injection into subcutaneous tissue.

The hexamer precipitate allows for a delay in the onset of action and a constant release of insulin over 24 hours. Insulin glargine is used in adult and pediatric patients 6 years and older with type 1 and type 2 diabetes mellitus (DM).

Insulin glargine is considered to be equipotent to other available basal insulins including NPH insulin, Lente insulin, and ultralente insulin; however, insulin glargine can provide basal insulin coverage consistently for 24 hours allowing for once-daily administration.

Also, insulin glargine does not have any significant peaks; rather it has a relatively constant concentration/time profile that is comparable to continuous subcutaneous insulin infusion (CSII) and more closely mimics endogenous basal insulin secretion.

Advantages of insulin glargine, when compared to other basal insulins, include once-daily administration, less variability in patient response, and a decreased incidence of hypoglycemia, including both nocturnal and severe hypoglycemia.

Insulin glargine and insulin detemir had similar rates of A1C reduction in a 52-week clinical trial of insulin-naive patients taking basal insulin as add-on therapy to oral glucose-lowering medications; A1C decreased by 1.5% in both treatment groups (7.1% for insulin glargine and 7.2% for insulin detemir).

No insulin has been shown to reduce the risk for cardiovascular disease (CVD), but data suggest that insulin glargine 100 units/mL and insulin degludec do not increase the risk for major cardiovascular events (MACE).

When targeting intensive glycemic control in patients with long-standing type 2 DM at high risk of CVD, insulin degludec is associated with a lower risk of severe hypoglycemia compared with insulin glargine 100 units/mL.

In the treatment of type 1 DM, insulin therapy may be initiated with a basal-bolus regimen of insulin glargine and then further individualized to achieve treatment goals. In the treatment of type 2 DM, insulin is generally reserved for patients who continue to have an A1C above target despite dual/triple therapy with metformin and other antidiabetic agents.

In patients who need the greater glucose-lowering effect of an injectable medication, GLP-1 receptor agonists (GLP-1 RA) are the preferred choice to insulin. Evidence from trials comparing GLP-1 RAs and insulin (basal, premixed, or basal-bolus) shows similar or even better efficacy in A1C reduction; GLP-1 RAs have a lower risk of hypoglycemia and are associated with reductions in body weight compared to weight gain with insulin.

In patients who cannot tolerate a GLP-1 RA, or who fail to meet glycemic targets with dual/triple therapy, insulin therapy with basal insulin, such as insulin glargine should be initiated and titrated to target. If the A1C remains above target, prandial insulin should be added.

Consider an initial injectable combination (i.e., GLP-1 RA plus basal insulin or prandial/basal insulin) if A1C is greater than 10% and 2% above target.

Consider the early introduction of insulin if there is evidence of ongoing catabolism, if symptoms of hyperglycemia are present, or when A1C levels (greater than 10%) or blood glucose levels (300 mg/dL or more) are very high.

In patients who are starting on insulin therapy and are taking a thiazolidinedione or sulfonylurea, discontinue or reduce the dose of the oral medication.

Mechanism of Action

Endogenous insulin regulates carbohydrate, fat, and protein metabolism by several mechanisms; in general, insulin promotes the storage and inhibits the breakdown of glucose, fat, and amino acids. Insulin lowers glucose concentrations by facilitating the uptake of glucose in muscle and adipose tissue and by inhibiting hepatic glucose production (glycogenolysis and gluconeogenesis).

Insulin also regulates fat metabolism by enhancing the storage of fat (lipogenesis) and inhibiting the mobilization of fat for energy in adipose tissues (lipolysis and free fatty acid oxidation).

Finally, insulin is involved in the regulation of protein metabolism by increasing protein synthesis and inhibiting proteolysis in muscle tissue.

Indications

• neonatal diabetes mellitus
• type 1 diabetes mellitus
• type 2 diabetes mellitus

Side Effects

1. anaphylactic shock
2. anaphylactoid reactions
3. angioedema
4. antibody formation
5. arthralgia
6. back pain
7. bronchospasm
8. cataracts
9. cough
10. cutaneous amyloidosis
11. depression
12. diarrhea
13. erythema
14. headache
15. hyperinsulinemia
16. hypertension
17. hypoglycemia
18. hypokalemia
19. hypotension
20. infection
21. influenza
22. injection site reaction
23. insulin resistance
24. insulin shock
25. lipodystrophy
26. peripheral edema
27. peripheral neuropathy
28. pharyngitis
29. rash
30. retinopathy
31. rhinitis
32. sinusitis
33. Somogyi effect
34. urticaria
35. weight gain
36. wheezing

Monitoring Parameters

• blood glucose
• glycosylated hemoglobin A1c (HbA1c)

Contraindications

• breast-feeding
• coma
• continuous subcutaneous insulin infusion (CSII) administration
• cresol hypersensitivity
• diabetic ketoacidosis
• diarrhea
• fever
• geriatric
• hepatic disease
• hyperosmolar hyperglycemic state (HHS)
• hypoglycemia
• hypokalemia
• infection
• intravenous administration
• neonates
• pregnancy
• renal failure
• renal impairment
• surgery
• thyroid disease
• tobacco smoking
• trauma
• visual impairment
• vomiting

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