Isophane Insulin (NPH)

Isophane Insulin (NPH) Brand Names

Humulin N | Iletin II NPH | Novolin N

What is Isophane Insulin (NPH)

Neutral Protamine Hagedorn (NPH) or isophane insulin is an intermediate-acting insulin that is produced by adding zinc and protamine to regular insulin that delays absorption and prolongs the duration of insulin action after subcutaneous administration.

The combination with protamine and low concentrations of zinc enhances the aggregation of insulin into dimers and hexamers after subcutaneous injection; a depot is formed after injection, and the insulin is released slowly. NPH insulin is used in patients with both type 1 and type 2 diabetes mellitus (DM).

The duration of action of NPH insulin is variable; some patients may require only 1 injection per day while others require 3 or more injections daily. Patients with established type 1 DM will often require more than 2 injections of NPH insulin daily when NPH is used as basal insulin.

NPH insulin is commonly administered twice daily in combination with rapid-acting insulin (e.g., regular insulin, insulin aspart, insulin glulisine, or insulin lispro) to patients with type 2 DM.

NPH insulin is considered to be equipotent to other basal insulins including Lente insulin, insulin detemir, and insulin glargine. NPH insulin is not the ideal basal insulin as it has variable absorption, unwanted peaks leading to hypoglycemia (including nocturnal hypoglycemia), and often an inadequate duration of action (even when administered twice daily) that may cause fasting hyperglycemia.

In the treatment of type 1 DM, insulin therapy may be initiated with a basal-bolus regimen of NPH insulin 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 NPH insulin should be initiated and titrated to target.

If the A1C remains above target, prandial insulin should be added. Consider initial injectable combination (i.e., GLP-1 RA plus basal insulin or prandial/basal insulin) if A1C is greater than 10% or 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

Indications

1. gestational diabetes
2. type 1 diabetes mellitus
3. type 2 diabetes mellitus

Side Effects

1. anaphylactoid reactions
2. antibody formation
3. cutaneous amyloidosis
4. diaphoresis
5. dyspnea
6. headache
7. hyperinsulinemia
8. hypertension
9. hypoglycemia
10. hypokalemia
11. hypotension
12. injection site reaction
13. insulin resistance
14. insulin shock
15. lipodystrophy
16. peripheral edema
17. pruritus
18. rash
19. sinus tachycardia
20. Somogyi effect
21. urticaria
22. weight gain
23. 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

Interactions

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