Summary

Insulin is an anabolic peptide hormone that is produced and secreted from beta cells located in the islets of Langerhans of the pancreas. It has important metabolic functions, which include promoting the storage of carbohydrates, amino acids, and fat in the liver, skeletal muscle, and adipose tissues. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Insulin therapy is an important part of treatment for individuals with insufficient or absent insulin production (e.g., diabetes mellitus, gestational diabetes). Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure and differ in onset, peak, and duration compared to human insulin. It is crucial that patients receiving insulin therapy undergo in-depth training to prevent potentially life-threatening conditions such as hypoglycemia as a result of an insulin overdose or drug interactions.

For further information on insulin therapy and regimens, see insulin therapy.

Overview

Types of insulin	Effect	Application	Special features
Rapid-acting insulin
Insulin lispro	Onset: 5–30 min Peak: 30 min–3 h Duration: 3–5 h	Intensified conventional insulin therapy	Injected before a meal time Used in combination with longer-acting insulin
Insulin aspart
Insulin glulisine
Short-acting insulin
Regular insulin	Onset: ∼30 min Peak: 2.5–5 h Duration: 4–24 h	“Standard insulin” for lowering blood glucose levels in an acute setting Conventional insulin therapy Intensified conventional insulin therapy	Mandatory interval between injections and meal times: ∼30 min Used in combination with longer-acting insulin Intravenous therapy available (only for this type of insulin)
Intermediate-acting insulin
NPH insulin	Onset: 1–2 h Peak: 4–12 h Duration: 14–24 h	Conventional insulin therapy Component of basal supported oral therapy (BOT) for treatment-resistant type 2 diabetes mellitus	Crystalline suspension Mandatory interval between injections and meal times: 30–60 min Used in combination with rapid or short-acting insulin Usually administered twice daily
Long-acting insulin
Insulin glargine	Onset: 1.5–4 h Peak: flat; not defined Duration: ∼ 24 h	Intensified conventional insulin therapy Component of basal supported oral therapy (BOT) for treatment-resistant type 2 diabetes mellitus	Insulin analogs More consistent efficacy profile and longer duration of effect compared to NPH insulin Used in combination with rapid or short-acting insulin Administered once or twice daily
Insulin detemir
Insulin degludec
Ultralente insulin
Mixed insulin
Mixed insulin	Biphasic effect Short-term effect like that of regular insulin/lispro/aspart Long-term effect like that of NPH insulin	Conventional insulin therapy	Contains regular insulin and NPH insulin mixed according to a defined ratio Example: Actraphane^® 30/70, contains 30% regular insulin and 70% NPH insulin Administered two or three times a day

Effects

Insulin is an anabolic peptide hormone; that is produced and secreted from beta cells in the islets of Langerhans of the pancreas in response to a rise in blood glucose
Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure; after injection they exert the same actions but differ in onset, peak and duration compared to human insulin
Insulin binds to insulin receptors (a type of tyrosine kinase receptor) located in various tissues in the body (e.g., liver, skeletal muscle, adipose tissue) and has the following actions:

	Increases	Decreases
Carbohydrate metabolism	Uptake of glucose into cell Glycogenesis Glycolysis	Glycogenolysis Gluconeogenesis: via dephosphorylation of fructose-1,6-bisphosphatase
Lipid metabolism	Lipid synthesis	Lipolysis Ketogenesis
Protein metabolism	Protein synthesis Uptake of amino acids	Proteolysis
Other effects	Secretion of gastric acid Cell growth and differentiation Uptake of potassium

References:^[1]^[2]

Side effects

Hypoglycemia
Weight gain
Lipodystrophy at the injection site
Pain and erythema at injection site
Hypokalemia
Allergic reactions (rare)
Edema (rare)

We list the most important adverse effects. The selection is not exhaustive.

Indications

Type 1 diabetes mellitus
Type 2 diabetes mellitus, if weight normalization, physical activity, and oral antidiabetic drugs do not keep blood glucose levels in the target range
- All type 2 diabetic patients with end stage renal failure (oral antidiabetic drugs are contraindicated in this case)
Pancreatic insufficiency with secondary diabetes
Gestational diabetes, if change of diet is not sufficient
Acute hyperkalemia: A drip containing regular insulin and a solution of glucose reduces blood potassium levels.
See also “insulin therapy” in diabetes mellitus.

Insulin regimens

Basal-bolus insulin regimen ^[3]^[4]

Calculate the total daily dose of insulin (TDD) needed.
- If the patient is already on a correction scale: Increase or decrease total daily dose by 10–20% as needed.
- If the patient is lean, has T1DM, age ≥ 70 years, and/or GFR < 60 mL/min: 0.2–0.3 units/kg
- If none of the above criteria applies, use the blood glucose level:
  - BG 140–200 mg/dL: 0.4 units/kg
  - BG > 200 mg/dL: 0.5 units/kg
Divide the total daily dose of insulin into basal insulin (50%) and nutritional insulin (50%).
- Basal insulin: Administer as long-acting insulin (e.g., glargine) at bedtime.
- Nutritional insulin: Administer as rapid-acting insulin (e.g., lispro) in equally divided doses before meals.
Add sliding scale insulin as supplemental insulin.
- Take 5% of the TDD (e.g., 50 → 2.5).
- Round down to the safest whole number (e.g., 2.5 → 2).
- For every 40 mg/dL (2.2 mmol/L) above the goal serum glucose of 140 mg/dL, increase the nutritional insulin scale by this increment.
Adjust as needed.
- If glucose persistently > 140 mg/dL and no episodes of hypoglycemia: Increase basal insulin by 20% and/or increase sliding scale insulin by 2 units.
- In cases of hypoglycemia < 70 mg/dL: Reduce basal insulin by 20% and/or sliding scale insulin by 2 units.

Decrease or hold nutritional insulin if the patient is NPO.

Sliding scale insulin regimen ^[4]

If the patient is eating all or most of each meal: administer as short-acting insulin (or rapid-acting insulin) before each meal and at bedtime
If the patient is not eating: administer as short-acting insulin every 6 hours

Blood glucose (mg/dL)	Insulin units
Blood glucose (mg/dL)	Insulin sensitive	Usual insulin	Insulin resistant
71–140	0	0	0
141–180	2	4	6
181–220	4	6	8
221–260	6	8	10
261–300	8	10	12
301-350	10	12	14
351-400	12	14	16

If the blood glucose is < 70 mg/dL, hold all insulin and administer hypoglycemia measures.

Weight-based NPH insulin regimen for glucocorticoid-induced hyperglycemia ^[5]

Convert glucocorticoid to equivalent prednisone dose (see glucocorticoids).
Calculate daily NPH dose based on prednisone dose equivalent and patient weight.
Administer glucocorticoid with NPH as a single dose in the morning.

Prednisone dose equivalent (mg/day)	NPH (units/kg/day)
10	0.1
20	0.2
30	0.3
≥ 40	0.4

NPH doses should be administered in addition to usual basal insulin in patients who are already receiving insulin.

Consider using glargine or detemir in patients receiving dexamethasone. Dexamethasone has a longer hyperglycemic effect than prednisone and most other commonly used systemic glucocorticoids.

Insulin regimens for enteral and parenteral nutrition

Enteral nutrition ^[6]^[7]

Determine basal insulin needs.
- For patients already on insulin: Continue prior dose or administer 30–50% of the total daily dose as long-acting insulin (e.g., glargine) daily.
- For patients not already on insulin, consider:
  - 5 units of NPH every 12 hours
  - or 10 units of glargine (or equivalent) daily
Add nutritional insulin
- For patients receiving continuous tube feedings
  1. Calculate the total daily nutritional insulin dose:
    - 1 unit of insulin per 10–15 g of carbohydrates per day
    - or 50–70% of the total daily dose
  2. Administer as rapid-acting insulin (e.g., lispro) in divided doses every 4–6 hours.
- For patients receiving bolus feeding
  1. Calculate the nutritional insulin dose to cover each meal: 1 unit of insulin per 10–15 g of carbohydrates per meal
  2. Administer as rapid-acting insulin (e.g., lispro) before each feeding.
Add sliding scale insulin as supplemental insulin.
- For patients on continuous tube feedings: Administer rapid-acting insulin (e.g., lispro) every 4 hours or regular insulin every 6 hours.
- For patients receiving bolus feedings: Administer rapid-acting insulin before every meal.
Adjust as needed to glycemic targets, changes in medication, and changes in nutrition.

Patients with type 1 diabetes mellitus require basal insulin even if (enteral) feeding is discontinued.

Total parenteral nutrition (TPN) ^[6]^[8]

Add short-acting insulin to IV parenteral nutrition solution.
- Diabetic patient: 1 unit per 10–15 g dextrose
- Nondiabetic patient: 0.5 units per 10 g dextrose
Add sliding scale insulin as supplemental insulin: Administer as short-acting insulin (e.g., regular insulin) every 6 hours or rapid-acting insulin (e.g., lispro) every 4 hours.
Adapt protocol to glycemic targets, changes in medication, and changes in nutrition.

Basal-bolus insulin regimen [3][4]

Sliding scale insulin regimen [4]

Weight-based NPH insulin regimen for glucocorticoid-induced hyperglycemia [5]