Insulin is an anabolic peptide hormone that is produced and secreted from β cells located in the islets of Langerhans of the pancreas. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Further important metabolic functions of insulin include the promotion of carbohydrate, amino acid, and fat storage in the liver, skeletal muscle, and adipose tissues. There are several insulin analogs (e.g., insulin glargine) with a different molecular structure but similar properties to human insulin, with differences mainly in the onset, peak, and duration of action. Insulin therapy is an important part of treatment for individuals with no or insufficient insulin production (e.g., diabetes mellitus, gestational diabetes). 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.
See also “” and “ .”
For synthesis and regulation of insulin see “.”
|Overview of the different types of insulin|
|Types of insulin||Pharmacokinetics ||Application ||Additional considerations |
|Insulin lispro|| || || |
|Regular insulin|| || |
|NPH insulin|| || |
|Insulin glargine|| || || |
|Mixed insulin|| |
Rapid-acting insulins are your favorite GAL pals (Glulisine, Aspart, Lispro).
Insulin function and metabolic effects
- Insulin binds to insulin receptors (a type of ) located in various tissues in the body (e.g., liver, skeletal muscle, adipose tissue, cell membranes). 
- In target tissues, insulin acts as an anabolic hormone.
|Metabolic actions of insulin|
|Protein metabolism|| |
Other physiologic actions of insulin
Cellular uptake of potassium 
- Sodium retention by the kidney 
- Ovarian androgen hypersecretion 
- Decreased fibrinolytic activity 
- Secretion of gastric acid 
- Cell growth and differentiation 
Cellular and insulin-mediated uptake of glucose
- Glucose may enter cells throughout the body via a variety of transporters.
- Different tissue types have unique glucose transporters (e.g., GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5), some of which are insulin-dependent and some of which are insulin-independent.
- See “Important glucose transporters” in " .”
The absorption time determines the onset, peak, and duration of effect. 
Prolonged insulin absorption time
Shorter insulin absorption time
- diabetes with secondary
- Acute : A drip containing regular insulin and a solution of glucose reduces blood potassium levels.
- See “Insulin therapy” in “ ” and “ .”
Certain drugs can either increase or decrease insulin demand. 
Increased insulin demand
- Immunosuppressive drugs (e.g., calcineurin inhibitors)
- Thyroid hormones
- Estrogen ( )
- Sympathomimetic drugs that interact with the β1-adrenergic receptor (e.g., dobutamine)
- Derivatives of nicotinic acid
Decreased insulin demand
- Antibiotics (e.g., cotrimoxazole and other sulfonamides , )
- Antimalarial drugs (e.g., , )
- MAO inhibitors
Either increased or decreased insulin demand
Insulin regimens should be tailored individually to each patient. There are a variety of options for patients with T2DM. Treatment of T1DM requires intensive insulin therapy with a multi injection regimen or insulin pump.
Basal insulin regimens 
- Description: Basal insulin is added to an oral antidiabetic drug regimen.
- Indication: T2DM with persistently elevated A1C levels despite adequate treatment with noninsulin antidiabetics
- Once-daily injection (recommended starting regimen)
- glargine) (e.g., OR bedtime
- Starting dose: 10 units/day OR 0.1–0.2 units/kg/day
- Twice-daily NPH.
: Consider for patients not meeting their glycemic target with bedtime
- Starting dose: 80% of the previously prescribed bedtime dose, with two-thirds given in the morning and one-third at bedtime
- Once-daily injection (recommended starting regimen)
- Adjust according to glycemic monitoring.
- If treatment remains insufficient despite appropriate adjustments , intensify treatment by either adding prandial insulin or considering a mixed regimen.
Not all noninsulin antidiabetics can be combined with insulin. Combination therapy with insulin and sulfonylureas should be avoided because of the risk of hypoglycemia and increased mortality! Once insulin is started, consider tapering and eventual discontinuation of sulfonylureas. Insulin combined with pioglitazone increases the risk of edema, weight gain, and congestive heart failure. Metformin is usually continued.
Addition of prandial insulin 
- Indication: T2DM that is not adequately controlled with basal insulin alone
- Basal insulin injections are continued at the previous dose.
- 4 units of short-acting or rapid-acting insulin before chosen meals
- Titration: Adjust according to glycemic monitoring.
Mixed insulin regimens 
- Twice-daily injections of a fixed combination of NPH mixed with either or ; can be self-mixed or premixed
- Simple regimens that require minimal patient education and time
- Indication: Consider for patients with T2DM who are not meeting glycemic targets with a basal insulin regimen.
- Starting dose
- Adjust according to glycemic target.
- If treatment results remain inadequate, consider a full basal-bolus regimen.
Intensive insulin therapy 
This regimen provides optimal glycemic control as well as more flexibility in the daily diet and exercise plan, and it reduces the risk of complications in patients with good adherence.
- Full basal-bolus regimen: basal regimen with additional short-acting or rapid-acting insulin bolus before every major meal
- Insulin pump 
The goal of intensive insulin therapy is to simulate physiological glucose metabolism (e.g., by keeping fasting blood glucose levels < 100 mg/dL (5.6 mmol/L) and postprandial blood glucose levels < 140 mg/dL (< 7.8 mmol/L).
Patients on a full basal-bolus regimen require intensive education, high motivation, and commitment, as this is the most complex and time-consuming treatment for diabetes and has an increased risk for hypoglycemia.
Full Basal-bolus insulin regimen 
Basal-bolus regimens may vary. Institutional standards should be followed and intensive insulin therapy tailored individually to each patient.
- Calculate the total daily dose of insulin (TDD) needed.
- If the patient is already on a correction scale: Increase or decrease TDD by 10–20% as needed.
- If the patient is aged ≥ 70 years, and/or has GFR < 60 mL/min: 0.2–0.3 units/kg
- If none of the above criteria apply, use the blood glucose level:
- BG 140–200 mg/dL: 0.4 units/kg
- BG > 200 mg/dL: 0.5 units/kg
- Divide the TDD of insulin into basal insulin (50%) and nutritional insulin (50%).
- Consider adding a correction bolus before each meal estimated with one of the following methods:
Insulin correction factor 
- Divide 1500 (for short-acting insulin) or 1800 (for rapid-acting insulin) by the total daily dose of insulin
- The result is the blood glucose level (in mg/dL) that 1 additional unit of insulin is expected to lower for a specific individual.
- 1–2 units of insulin typically lower the blood glucose level by ∼ 30–50 mg/dL
- Insulin-to-carbohydrate ratio (ICR) 
- Insulin correction factor 
- Adjust as needed.
Decrease or hold nutritional insulin if the patient is NPO.
Principles of insulin adjustment
- Preprandial glucose
- Mainly affected by the basal insulin dose
- Daily capillary early morning measurements and measurements before applying an insulin dose are advised.
- Postprandial glucose is mainly affected by meal intake and prandial insulin dose.
Certain conditions require temporary insulin adjustments.
- Increased insulin demand
Decreased insulin demand
Physical exercise: Increase carbohydrate intake and/or reduce prandial and/or basal insulin either before or after exercise. 
- Moderate intensity exercise: Reduce 50% of meal insulin.
- High intensity exercise: Reduce 75% of meal insulin.
- Patients on multiple daily insulin injections: reduce daily basal insulin by 20% on the day of exercise 
- Encourage glucose self-monitoring to reach appropriate insulin reduction and/or need for snacks.
- Vomiting and diarrhea: can lead to decreased glucose uptake, increasing the risk of hypoglycemia
- Physical exercise: Increase carbohydrate intake and/or reduce prandial and/or basal insulin either before or after exercise. 
- Increased insulin demand
- Fasting, e.g., for surgery (see “ ” and “Fasting guidelines for elective surgery.”)
Sliding-scale insulin regimen 
- 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.
|Administration of sliding scale insulin (example)|
|Blood glucose (mg/dL)||Insulin units|
|Insulin sensitive||Usual insulin||Insulin resistant|
If blood glucose is < 70 mg/dL, hold all insulin and administer measures to control hypoglycemia.
Insulin regimens for glucocorticoid-induced hyperglycemia
Basal-bolus insulin regimen (preferred)
- Consider splitting the total daily dose of insulin 30/70 (i.e., 30% long-acting insulin and 70% prandial short-acting insulin).
- Patients usually require about 0.4 units/kg/day but in patients receiving dexamethasone, insulin doses as high as 1.0–1.2 units/kg/day may be necessary. 
- The total required insulin dosage depends on individual patient factors (e.g., prior insulin sensitivity) and the potency of the steroid.
- Sliding-scale insulin regimen: may be adequate for short-term management
- Weight-based NPH insulin regimen 
NPH doses should be administered in addition to usual basal insulin in patients who are already receiving insulin.
Insulin regimens for enteral and parenteral nutrition
Enteral nutrition 
- Determine basal insulin needs.
- Add nutritional insulin.
- For patients receiving continuous tube feedings
- For patients receiving bolus feeding
- Add sliding scale insulin as supplemental insulin.
- 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) 
- 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.