Version December 2023
Hyperglycemia: Limited data available: Note: Neonates are extremely sensitive to the effects of insulin; initiate therapy at the lower end of infusion rate and monitor closely; routine use in neonates is not recommended:
Intermittent IV infusion: 0.05 to 0.1 units/kg infused over 15 minutes every 4 to 6 hours as needed; Note: Should be used as initial management; monitor blood glucose every 30 minutes to 1 hour following doses (Ref).
Continuous IV infusion: Initial rate: 0.01 to 0.05 units/kg/hour, monitor blood glucose every 30 minutes and titrate in 0.01 units/kg/hour increments, usual range: 0.01 to 0.1 units/kg/hour (Ref).
Hyperkalemia, treatment: Limited data available:
IV: 0.1 units/kg combined with dextrose. Note: Usual ratio is 1 unit of insulin for every 5 g of dextrose for intermittent IV doses (Ref).
Continuous IV infusion: Initial bolus: 0.05 units/kg in combination with dextrose followed by a continuous IV infusion of insulin at 0.1 unit/kg/hour in combination with dextrose (Ref); insulin infusions as low as 0.05 units/kg/hour in conjunction with dextrose infusion have been used in premature neonates (n=7; GA: ≤28 weeks) (Ref). Note: Usual ratio is 1 unit of insulin for every 2 to 4 g of dextrose for continuous infusion (Ref).
Insulin regular is a short-acting insulin formulation. Insulin doses should be individualized based on patient needs; adjustments may be necessary with changes in physical activity, meal patterns, acute illness, or with changes in renal or hepatic function. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision. Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.
Diabetes mellitus, type 1: Infants, Children, and Adolescents: Note: Insulin regular is generally used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or via a continuous SubQ insulin infusion pump. The daily doses presented are expressed as the total units/kg/day of all insulin formulations combined.
General insulin dosing:
Initial total daily insulin: SubQ: Initial: 0.4 to 0.5 units/kg/day in divided doses (Ref); usual range: 0.4 to 1 units/kg/day in divided doses (Ref); lower doses (0.25 units/kg/day) may be used, especially in young children, to avoid potential hypoglycemia (Ref); higher doses may be necessary for some patients (eg, obese, concomitant steroids, puberty, sedentary lifestyle, following diabetic ketoacidosis presentation) (Ref).
Usual total daily maintenance range: SubQ: Doses must be individualized; however, an estimate can be determined based on phase of diabetes and level of maturity (Ref).
Partial remission phase (Honeymoon phase): <0.5 units/kg/day.
Prepubertal children (not in partial remission):
Infants ≥6 months and Children ≤6 years: 0.4 to 0.8 units/kg/day.
Children ≥7 years: 0.7 to 1 units/kg/day.
Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and, in some cases, up to 2 units/kg/day.
Division of daily insulin requirement (multiple daily injections):
Basal insulin: Generally, ~30% to 50% of the total daily insulin dose is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (Ref).
Prandial insulin: The remaining portion of the total daily dose is then divided and administered before or at mealtimes (depending on the formulation) as rapid-acting (eg, aspart, glulisine, lispro) or short-acting (regular). In most type 1 patients, the use of a rapid-acting insulin analog is preferred over regular insulin to reduce hypoglycemia risk (Ref).
Dose titration: Treatment and monitoring regimens must be individualized to maintain premeal and bedtime glucose in target range; titrate dose to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.
Surgical patients (Ref): Note: Diabetic patients should be scheduled as the first case of the day.
Minor surgeries:
Morning procedure: Omit short-acting insulin unless it is need to correct hyperglycemia and administer the usual morning dose of long-acting insulin or 50% to 70% of the usual morning dose of insulin NPH; alternatively, administer IV insulin (regular) infusion beginning at least 2 hours prior to surgery.
Afternoon procedure: If allowed to eat breakfast, administer 50% of the usual morning dose of short-acting insulin (regular) with breakfast. Begin an IV insulin (regular) infusion beginning at least 2 hours prior to surgery.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to risk of changes related to surgery (ie, postoperative stress, medication changes, inactivity).
Major surgeries:
Evening prior to surgery: Administer the usual evening and/or bedtime insulin(s); patients on continuous subcutaneous insulin infusion (CSII) may continue normal insulin basal rates overnight; if there is a concern for hypoglycemia, basal rate may be reduced by 20% at ~3 am.
Morning of surgery: Omit morning insulin (short- and long-acting) and start IV insulin (regular) infusion and IV dextrose at least 2 hours prior to surgery; patients on CSII, should discontinue CSII when IV insulin infusion is started.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to risk of changes related to surgery (ie, postoperative stress, medication changes, inactivity).
Diabetes mellitus, type 2: Children ≥10 years and Adolescents: SubQ: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications. Initial therapy in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c ≥8.5% and symptoms excluding acidosis) may include once-daily long-acting basal insulin (preferred) or intermediate-acting insulin (eg, NPH) in combination with lifestyle changes and metformin. In patients who fail to achieve glycemic goals with metformin and basal insulin, may consider initiating prandial insulin (rapid-acting insulin or regular insulin in select situations) and titrate to achieve goals. Once initial goal reached, insulin should be slowly tapered over 2 to 6 weeks by decreasing the insulin dose by 10% to 30% every few days and the patient transitioned to lowest effective insulin doses or metformin monotherapy if able (Ref). Note: Patients who are ketotic or present with ketoacidosis require aggressive management with SubQ or IV insulin to correct the hyperglycemia and ketosis/ketoacidosis. Once ketosis/ketoacidosis resolves, metformin should be initiated as appropriate, while continuing insulin via the SubQ route; insulin can be titrated as appropriate once goals are achieved.
Diabetic ketoacidosis (DKA): Limited data available: Infants, Children, and Adolescents: Note: Severe DKA should be treated with IV regular insulin. Serum glucose is not a direct indicator of the overall metabolic abnormalities and may decrease more rapidly than correction of the metabolic abnormalities such as acid-base abnormalities, blood β-hydroxybutyrate (BOHB), and anion gap. As part of overall DKA management, dextrose should be added to IV fluids to prevent hypoglycemia, usually once serum glucose is between 250 to 300 mg/dL, but it may be required sooner if serum glucose has decreased precipitously. Generally, only dextrose 5% is necessary and is added to NS or 1/2NS; however, dextrose 10% or 12.5% may be necessary in some cases (Ref). Refer to institution-specific protocols where appropriate.
Continuous IV infusion:
Initial: 0.05 to 0.1 units/kg/hour (start insulin infusion at least 1 hour after starting fluid replacement therapy); DO NOT bolus at start of therapy; continue the rate at 0.05 to 0.1 units/kg/hour, if tolerated, until resolution of ketoacidosis (pH >7.3; bicarbonate >15 mEq/L, BOHB < 1 mmol/L, and/or closure of anion gap); serum BOHB should decrease by approximately 0.5 mmol/L/hour; adjust insulin if the expected rate of biochemical correction does not occur. Note: Some patients (eg, some young children with DKA, older children with established diabetes) may have marked sensitivity to insulin requiring lower infusion rates; these lower infusion rates should only be used provided that resolution of the acidosis continues (Ref).
Transition from IV to SubQ insulin: Once ketoacidosis has resolved and oral intake is tolerated, transition to a SubQ insulin regimen. An overlap between discontinuation of IV insulin and administration of SubQ insulin is recommended to ensure adequate plasma insulin levels. A dose of basal (long-/intermediate-acting) insulin should be administered in addition to rapid-/short-acting insulin. To prevent rebound hyperglycemia, adjust timing of SubQ insulin administration prior to infusion discontinuation dependent on type of insulin used; for SubQ regular insulin: 1 to 2 hours, or for rapid-acting insulin: 15 to 30 minutes; with intermediate- or long-acting insulin, the overlap should be longer and the rate of IV insulin administration gradually decreased (eg, administer basal in the evening and discontinue the IV infusion the next morning); optimal timing for transition is around mealtime for convenience. Benefits have been seen with early administration of basal insulin during IV insulin infusion (Ref).
SubQ: Note: SubQ administration for DKA treatment may be considered for patients with uncomplicated DKA in whom peripheral circulation is adequate and continuous IV regular insulin administration is not possible (Ref).
Initial: 0.8 to 1 unit/kg/day in divided doses every 4 hours; titrate dose by 10% to 20% based on blood glucose concentration prior to next insulin dose.
Calcium channel blocker or beta-blocker toxicity (high-dose insulin therapy): Limited data available (Ref):
Note: Consultation with a clinical toxicologist or poison control center is highly recommended.
Prior to initiating high-dose insulin therapy, dextrose supplementation is necessary in infants and children with serum glucose <400 mg/dL and in adolescents with serum glucose <200 mg/dL (Ref). Monitor serum glucose closely during therapy, with increased frequency of monitoring following the initial insulin bolus and during insulin infusion rate changes (Ref). Concomitant dextrose infusion or intermittent dextrose boluses are necessary to prevent hypoglycemia; maintain euglycemia goal of 100 to 250 mg/dL (Ref). When discontinuing the insulin infusion, the hypoglycemic effects may last for at least 24 hours after it is stopped; continue to monitor glucose levels closely during that time.
Correct hypokalemia prior to initiation of insulin therapy; monitor serum potassium closely during insulin infusion and supplement as needed to maintain normal serum potassium levels (Ref). To avoid fluid overload, concentrate IV fluids, including dextrose boluses or supplementation as appropriate and as venous access allows (Ref).
Infants, Children, and Adolescents: IV: Initial loading dose: 0.5 to 1 unit/kg bolus followed by a continuous IV infusion starting at 0.5 to 1 unit/kg/hour; titrate to clinical response; it has been suggested if patient remains hypotensive after initial 30 minutes of infusion to increase rate to 2 units/kg/hour, with additional rate increases as needed to maintain normotension. In severe cases, higher doses (continuous infusion >10 units/kg/hour) may be necessary (Ref).
Hyperkalemia, treatment: Limited data available: Note: Experts suggest using a ratio of 1 unit of insulin for every 5 g of dextrose (Ref).
Infants, Children, and Adolescents: IV: 0.1 unit/kg (maximum dose: 10 units/dose) combined with dextrose administered over 30 minutes (Ref). An alternate approach is dextrose bolus followed by 0.2 units of insulin per g of dextrose administered over 15 to 30 minutes then infused continuously as a similar amount per hour (Ref). In adults, the usual dose is 10 units of insulin mixed with 25 g of dextrose (50 mL of D50W) administered over 15 to 30 minutes (Ref).
Hyperosmolar hyperglycemic state (HHS): Limited data available: Infants, Children, and Adolescents:
Note: Only regular IV insulin should be used. Insulin administration should be initiated when serum glucose concentration is no longer declining at a rate ≥50 mg/dL/hour with fluid administration alone; earlier initiation may be required in patients with severe ketosis and acidosis. Refer to institution-specific protocols where appropriate.
Continuous IV infusion: Initial: 0.025 to 0.05 units/kg/hour; titrate dose to achieve a decrease in serum glucose concentration at a rate of 50 to 75 mg/dL/hour; discontinue insulin if serum glucose concentration decreases >100 mg/dL/hour. Insulin boluses are not recommended (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling; insulin requirements are reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely. Based on experience in adult patients, dosage adjustment may be necessary.
There are no dosage adjustments provided in manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
(For additional information see "Insulin regular: Drug information")
Note: Regular insulin U-100 is not interchangeable with concentrated U-500 regular insulin. Regular insulin U-100 (100 units/mL) is a short-acting insulin, whereas concentrated U-500 regular insulin has an onset similar to short-acting insulins and a duration similar to intermediate-acting insulins. Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose.
Calcium channel blocker or beta-blocker overdose/toxicity (off-label use): Note: Optimal dosage regimen has not been determined; use for patients who are refractory to initial therapies (eg, atropine, calcium, vasopressors). Consultation with a clinical toxicologist or poison control center is highly recommended.
IV (U-100): 1 unit/kg bolus, followed by a continuous infusion at 0.5 to 1 unit/kg/hour (as premixed solution or diluted U-100 product for IV infusion) titrated to clinical response. Higher doses (eg, boluses of up to 10 units/kg and continuous infusions of >10 units/kg/hour) have been administered with good outcomes and minimal adverse effects. Once hemodynamic parameters have stabilized, gradually decrease insulin infusion (Ref).
Note: Correct hypokalemia prior to initiation of insulin therapy. For patients with baseline blood glucose <200 mg/dL, administer 50 mL of dextrose 50% IV prior to initiation of insulin therapy. Start a dextrose infusion when insulin therapy is initiated to maintain euglycemia; maintain normokalemia and euglycemia during insulin infusion and after withdrawal of insulin. Monitor blood glucose and electrolytes frequently, especially at the initiation of therapy. Concentrate all IV fluids to avoid fluid overload (Ref).
Diabetes mellitus, type 1, treatment:
Note: Regular insulin must be used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injections regimen) or in a continuous SUBQ infusion device. The total daily doses (TDDs) presented below are expressed as the total units/kg/day of all insulin formulations combined.
General insulin dosing (off label):
Initial TDD: SUBQ (U-100): ~0.4 to 0.5 units/kg/day in divided doses; conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid the potential for hypoglycemia; higher initial doses may be required in patients with obesity, or who are sedentary or presenting with ketoacidosis (Ref).
Usual TDD maintenance range: SUBQ (U-100): 0.4 to 1 units/kg/day in divided doses (Ref).
Division of TDD (multiple daily injections):
Basal insulin: Generally, 40% to 50% of the TDD is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (Ref).
Prandial insulin: The remaining portion (ie, 50% to 60%) of the TDD is then divided and administered before, at, or just after mealtimes depending on the formulation (eg, short-, rapid-, ultra-rapid acting) (Ref).
Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen that most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.
Diabetes mellitus, type 2, treatment:
Note: Regular insulin U-100 is not interchangeable with concentrated U-500 regular insulin.
Regimens involving regular insulin U-100 (100 units/mL):
Note: May be used if glycemic targets are not met despite adequately titrated basal insulin (eg, fasting glucose levels at goal, basal insulin dose >0.5 units/kg/day) (Ref). For regimens containing basal and prandial insulin, consider discontinuing noninsulin agents other than metformin, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors (Ref).
Initial:
Note: Prandial insulin regimens are typically initiated as one daily injection administered before the largest meal; additional mealtime injections may be added based on results of glucose monitoring. In patients with HbA1c <8% when prandial insulin is initiated, consider reducing the basal insulin daily dose by 4 units/day or by 10% (Ref).
SUBQ (U-100): 4 to 6 units or 10% of the basal insulin dose (Ref).
Dosage adjustment: Note: Individualize dosage adjustments based on patient-specific factors (eg, glucose levels, carbohydrate intake) (Ref).
For persistently elevated glucose levels: SUBQ (U-100): Consider intensification of dietary modifications and/or increasing the corresponding mealtime dose(s) by 1 to 2 units or by 10% to 15% every 3 days to achieve glycemic targets while avoiding hypoglycemia (Ref). Note: More aggressive dose increases (eg, by ≥5 units) may be required in patients already taking >20 units/dose of regular insulin (Ref).
For hypoglycemia: SUBQ (U-100): For unexplained mild to moderate hypoglycemia, consider decreasing the corresponding mealtime dose(s) by 10% to 20% (Ref); for hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, consider decreasing the corresponding mealtime dose(s) by 20% to 50% (Ref).
Conversion from other insulin regimens to concentrated U-500 (500 units/mL) regular insulin:
Note: May be considered in patients requiring a total daily insulin dose >200 units/day. Discontinue all other insulin products prior to initiation (Ref). Patient should be under the care of a clinician experienced with using concentrated U-500 regular insulin.
Initial: SUBQ (concentrated U-500): Initial dosing depends on proximity to glycemic targets. One strategy is to administer the current total daily insulin dose as concentrated U-500 regular insulin, rounded down to the nearest 5 units, in 2 divided doses (eg, 60% prior to morning meal, 40% prior to evening meal or 50% before morning and evening meals) or 3 divided doses (eg, 40% prior to morning meal and 30% prior to midday and evening meals) (Ref). Note: In patients close to glycemic targets (eg, HbA1c ≤8%), consider reducing the initial daily concentrated U-500 regular insulin dose by 10% to 50% (Ref); some experts reduce the initial U-500 regular insulin dose by 20% even in patients far from glycemic targets (Ref).
Dosage adjustment: Note: Individualize dosage adjustments based on glucose levels (Ref).
For persistently elevated glucose levels: SUBQ (concentrated U-500): Increase daily dose by 10% to 20% weekly while avoiding hypoglycemia; in patients receiving 3 injections/day, consider increasing only 2 of the 3 daily doses (Ref).
For hypoglycemia: SUBQ (concentrated U-500): For unexplained mild to moderate hypoglycemia, consider decreasing daily dose by 10% to 30% (Ref); for severe hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, consider decreasing daily dose by 20% to 50% (Ref).
For a missed meal: SUBQ (concentrated U-500): Decrease dose by 50% for that meal (Ref).
Patients with diabetes receiving enteral feedings: Note: TDD of insulin is divided into a basal component (intermediate- or long-acting insulin) and nutritional and correctional components (regular insulin or rapid-acting insulins).
Nutritional: SUBQ (U-100): 1 unit of regular insulin per 10 to 15 g of carbohydrate prior to each bolus feeding; in patients receiving continuous feeds, administer every 6 hours based on the amount of carbohydrate administered over each 6-hour period (Ref).
Correctional: SUBQ (U-100): Administer correctional insulin as needed prior to each feeding (for bolus feeds) or every 6 hours (for continuous feeds) (Ref). Dosing is individualized; one example of an empiric correctional dose is 1 to 2 units per 40 to 50 mg/dL above target glucose level; patients with known insulin resistance or who are receiving glucocorticoids may require higher correctional doses (eg, 4 units per 50 mg/dL above target glucose level) (Ref).
Patients with diabetes receiving parenteral feedings:
IV (U-100; added to TPN solution): 1 unit of regular insulin per 10 g of carbohydrate added to TPN IV solution; adjust dose daily (Ref). One option is to increase the amount of regular insulin added to the TPN by two-thirds of the amount of the correctional insulin used on the previous day (Ref).
SUBQ (U-100): Administer correctional regular insulin every 6 hours as needed for hyperglycemia (Ref). Dosing is individualized; one example of an empiric correctional dose is 1 to 2 units per 40 to 50 mg/dL above target glucose level; patients with known insulin resistance or who are receiving glucocorticoids may require higher correctional doses (eg, 4 units per 50 mg/dL above target glucose level) (Ref).
Patients with diabetes undergoing surgery and using an insulin pump: SUBQ: For short procedures (eg, <2 hours), continue the usual pump “basal” insulin infusion rate, with or without a temporary 20% to 40% rate reduction, on the morning of the procedure. For long and complex procedures, consider transitioning from the insulin pump to an IV regular insulin infusion perioperatively (Ref).
Cadaveric organ recovery (hormonal resuscitation) (off-label use): IV (premixed solution or diluted U-100 product for IV infusion): Continuous infusion of 1 unit/hour (minimum dose) to maintain blood glucose of 120 to 180 mg/dL or 20 units as a bolus dose (after an IV bolus of dextrose 25 g) administered to the brain-dead donor who is hemodynamically unstable requiring significant vasopressor support; give concomitantly with levothyroxine or liothyronine (preferred), vasopressin, and methylprednisolone (Ref).
Diabetic ketoacidosis or hyperosmolar hyperglycemic state (off-label use):
Note: Begin correction of fluid deficits, if present. If serum potassium is <3.3 mEq/L on initial presentation, delay insulin administration until serum potassium reaches ≥3.3 mEq/L. Address other electrolyte abnormalities, as needed, during insulin administration. Administer IV insulin until diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) has resolved. If serum glucose is <250 mg/dL when IV insulin is started, initiate dextrose-containing IV fluids (Ref). An example of a dosing regimen is as follows; refer to institutional protocols (Ref).
IV (U-100):
Note: Administer continuous infusions using premixed solution or diluted U-100 product for IV infusion.
Initial: 0.1 units/kg IV bolus, followed by 0.1 units/kg/hour via IV infusion, or 0.14 units/kg/hour via IV infusion (no bolus) (Ref).
Dosage adjustment: Increase the IV infusion rate (eg, by double) each hour if serum glucose does not decrease by ~50 to 75 mg/dL in the first hour. Once serum glucose approaches 200 to 250 mg/dL (DKA) or 250 to 300 mg/dL (HHS), may decrease IV infusion (eg, to 0.02 to 0.05 units/kg/hour) and administer dextrose-containing IV fluids until DKA or HHS has resolved (Ref).
Transition from IV to SUBQ insulin: After resolution of the hyperglycemic crisis, may initiate a SUBQ insulin regimen (eg, with basal and prandial insulin); avoid ultra–long-acting basal insulins (eg, degludec, insulin glargine U-300 [300 units/mL]) in this setting due to their long time to reach maximal glycemic effect. Continue the IV insulin infusion for ~1 to 4 hours after the first SUBQ insulin dose to avoid rebound hyperglycemia or ketoacidosis (Ref).
Hyperglycemia, hospitalized patients (off-label use):
Note: For use in patients with persistent hyperglycemia (eg, blood glucose ≥140 to 180 mg/dL for >12 to 24 hours) with or without a history of diabetes; use of institution-specific protocols to achieve glycemic targets and minimize hypoglycemia is encouraged (Ref).
IV ( premixed solution or diluted U-100 product for IV infusion):
Note: IV administration of regular insulin is preferred over SUBQ in critically ill patients and may be considered in some perioperative patients (Ref).
IV continuous infusion: Initial: 1 to 4 units per hour, then titrate to achieve target blood glucose (eg, 140 to 180 mg/dL) (Ref).
Transition from IV to SUBQ insulin: Before discontinuation, transition stable ICU patients to a protocol-driven ‘basal-bolus’ insulin regimen, based on insulin infusion history and carbohydrate intake, to maintain glucose levels in target range; avoid ultra–long-acting basal insulins (eg, degludec, insulin glargine U-300 [300 units/mL]) in this setting due to their long time to reach maximal glycemic effect (Ref). Note: Administer initial dose of basal insulin ≥2 to 4 hours before discontinuing IV insulin infusion (Ref).
SUBQ:
Note: SUBQ administration of regular insulin may be considered in noncritically ill patients or in critically ill patients who have low insulin requirements and do not have conditions affecting absorption (eg, shock, edema) (Ref).
Correctional insulin:
Note: For use in addition to scheduled basal and nutritional insulin to achieve glycemic targets; prolonged use of correctional-only (ie, sliding scale) insulin regimens without basal insulin is discouraged (Ref).
SUBQ (U-100): Refer to institution-specific protocols; one example of an empiric correctional dose is 1 to 2 units per 40 to 50 mg/dL above target glucose level; dose is typically administered with meals (or bolus feeds) or every 6 hours (if NPO or receiving continuous feeds); patients with known insulin resistance or who are receiving glucocorticoids may require higher correctional doses (eg, 4 units per 50 mg/dL above target glucose level) (Ref).
Nutritional insulin:
Initial daily dosage:
Patients not receiving nutritional insulin prior to hospitalization:
Patients eating meals: SUBQ (U-100): 0.03 to 0.1 units/kg/meal administered with or just after meals (Ref). Note: Dose is individualized; consider doses at the lower end of this range in older patients and in those with renal impairment; consider doses at the higher end of this range in patients receiving glucocorticoids (Ref).
Patients receiving enteral feeds : SUBQ (U-100): 1 unit of regular insulin per 10 to 15 g of carbohydrate prior to each bolus feeding; in patients receiving continuous feeds, administer every 6 hours based on the amount of carbohydrate administered over each 6-hour period (Ref).
Patients receiving nutritional insulin prior to hospitalization: SUBQ (U-100): Continue the prehospitalization nutritional insulin dose; an empiric 20% to 50% dose reduction may be considered in patients with impaired renal function, poor nutritional intake, or admission glucose levels <100 mg/dL; higher doses may be required in patients receiving glucocorticoids (Ref).
Dosage adjustment: Adjust daily dose by 10% to 20% every 2 to 3 days to achieve glycemic targets. Consider reducing dosage for glucose levels <100 mg/dL to avoid hypoglycemia; in patients with glucose levels <40 mg/dL, larger dose reductions (eg, by 20% to 40%) may be needed (Ref).
Hyperkalemia, severe/emergent (off-label use): Note: Use in patients with hyperkalemia-associated ECG changes or other clinical signs consistent with hyperkalemia; or serum potassium >6.5 mEq/L; or serum potassium >5.5 mEq/L, plus significant kidney function impairment and either ongoing tissue breakdown (eg, rhabdomyolysis) or ongoing potassium absorption (eg, substantial GI bleeding) (Ref). Causes a temporary shift of serum potassium intracellularly. Consider use in combination with IV calcium to stabilize myocardial cell membranes and other methods of decreasing serum potassium and enhancing potassium removal/excretion as clinically indicated (Ref). Safety: Serum glucose monitoring, continuous cardiac monitoring, and serial ECGs are warranted (Ref). Administration of insulin for the treatment of hyperkalemia has been associated with errors (eg, therapy delays, dosing, wrong routes). Institutions should develop protocols and standard order sets to help reduce errors (Ref). Practice may vary; refer to institutional protocols.
IV (U-100): 10 units given as an IV bolus, along with separate administration of 25 to 50 g dextrose administered over 5 minutes (Ref). After initial dose of dextrose, some experts administer 10% dextrose continuous IV infusion at 50 to 100 mL/hour for ~5 hours (Ref). Note: Consider omitting dextrose if blood glucose is ≥250 mg/dL (Ref).
Patients with risk factors for hypoglycemia (eg, pretreatment serum glucose <140 mg/dL, kidney impairment, lower body weight):
IV (U-100): 5 units given as an IV bolus, along with separate administration of 25 g dextrose administered over 5 minutes (Ref). After initial dose of dextrose, some experts administer 10% dextrose continuous IV infusion at 50 to 100 mL/hour for ~5 hours (Ref).
Duration: May repeat dosing every 2 to 4 hours as needed; monitor serum potassium and blood glucose every hour for up to 6 hours after insulin has been administered (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as insulin requirements may be reduced due to changes in insulin clearance or metabolism. The following adjustments have been recommended.
SUBQ, IV:
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 10 to 50 mL/minute: Administer 75% of normal dose and monitor glucose closely.
CrCl <10 mL/minute: Administer 50% of normal dose and monitor glucose closely.
Hemodialysis: Because of a large molecular weight (6,000 daltons), insulin is not significantly removed by hemodialysis; supplemental dose is not necessary
Peritoneal dialysis: Because of a large molecular weight (6,000 daltons), insulin is not significantly removed by peritoneal dialysis; supplemental dose is not necessary
Continuous renal replacement therapy: Administer 75% of normal dose and monitor glucose closely; supplemental dose is not necessary
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); dosage requirements may be reduced and patients may require more frequent dose adjustment and glucose monitoring.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Peripheral edema
Dermatologic: Injection site pruritus
Endocrine & metabolic: Amyloidosis (localized at injection site), hypoglycemia, hypokalemia, weight gain
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Immunologic: Immunogenicity
Local: Erythema at injection site, hypertrophy at injection site, lipoatrophy at injection site, swelling at injection site
Hypersensitivity to regular insulin or any component of the formulation; during episodes of hypoglycemia.
Concerns related to adverse effects:
• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content, timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long-standing diabetes, diabetic nerve disease, patients taking beta-blockers, or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypersensitivity: Severe, life-threatening, generalized allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy, treat the patient with supportive care and monitor until signs and symptoms resolve.
• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia, and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium frequently with IV insulin use and supplement potassium when necessary.
Disease-related concerns:
• Bariatric surgery:
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2020). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of ≥75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones, may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Hepatic impairment: Use with caution in patients with hepatic impairment; increased risk of hypoglycemia. Dosage requirements may be reduced and patients may require more frequent dose adjustment and glucose monitoring.
• Renal impairment: Use with caution in patients with renal impairment; increased risk of hypoglycemia. Dosage requirements may be reduced and patients may require more frequent dose adjustment and glucose monitoring.
Special populations:
• Hospitalized patients: Prolonged use of a correctional-only (ie, sliding scale) insulin regimen in the inpatient setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin use is preferred, with correctional doses (insulin regular or rapid-acting insulin) as needed. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin along with nutritional and correctional components (insulin regular or rapid-acting insulin) is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia. A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2022).
Dosage form specific issues:
• Multiple-dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).
• Product variation: Human insulin differs from animal-source insulin. Any change of insulin should be made cautiously; changing manufacturers, type, and/or method of manufacture may result in the need for a change of dosage. Verify product label prior to administration to prevent medication errors.
• U-500 regular insulin: U-500 regular insulin is a concentrated insulin formulation which contains 500 units of insulin per mL and is intended for SUBQ administration only; do not administer IV or IM. U-500 regular insulin is generally not recommended for use in an insulin pump but may be used in select patients under the supervision of an experienced provider (AACE [Grunberger 2010]). Prescribe only to patients who require >200 units of insulin per day. Doses from a U-500 regular insulin vial should be drawn up only with a dedicated U-500 insulin syringe. Do not mix or dilute U-500 regular insulin with other insulin formulations. Insulin U-500 also has a delayed onset and longer duration of action compared to regular insulin U-100, and has both prandial and basal properties (ADA 2022). Do not perform dose conversions when using the KwikPen, the dose window shows the number of units to be injected. Do not transfer insulin from the KwikPen to a syringe for administration.
Other warnings/precautions:
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
HumuLIN R: 100 units/mL (3 mL, 10 mL) [contains metacresol]
NovoLIN R: 100 units/mL (10 mL) [contains metacresol]
NovoLIN R ReliOn: 100 units/mL (10 mL) [contains metacresol]
Solution, Intravenous [preservative free]:
Myxredlin: 100 units/100 mL in NaCl 0.9% (100 mL)
Solution, Subcutaneous:
HumuLIN R U-500 (CONCENTRATED): 500 units/mL (20 mL) [contains metacresol]
Solution Pen-injector, Injection:
NovoLIN R FlexPen: 100 units/mL (3 mL) [contains metacresol]
NovoLIN R FlexPen ReliOn: 100 units/mL (3 mL) [contains metacresol]
Solution Pen-injector, Subcutaneous:
HumuLIN R U-500 KwikPen: 500 units/mL (3 mL) [contains metacresol]
No
Solution (HumuLIN R Injection)
100 units/mL (per mL): $17.84
Solution (HumuLIN R U-500 (CONCENTRATED) Subcutaneous)
500 units/mL (per mL): $89.22
Solution (Myxredlin Intravenous)
100UT/100ML 0.9% (per mL): $0.42
Solution (NovoLIN R Injection)
100 units/mL (per mL): $16.52
Solution (NovoLIN R ReliOn Injection)
100 units/mL (per mL): $16.52
Solution Pen-injector (HumuLIN R U-500 KwikPen Subcutaneous)
500 units/mL (per mL): $114.84
Solution Pen-injector (NovoLIN R FlexPen Injection)
100 units/mL (per mL): $20.82
Solution Pen-injector (NovoLIN R FlexPen ReliOn Injection)
100 units/mL (per mL): $20.82
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
HumuLIN R: 100 units/mL (3 mL, 10 mL)
NovoLIN GE Toronto: 100 units/mL (10 mL) [contains metacresol]
Solution Cartridge, Injection:
NovoLIN GE Toronto Penfill: 100 units/mL (1.5 mL, 3 mL)
Solution Pen-injector, Injection:
HumuLIN R KwikPen: 100 units/mL (3 mL) [contains metacresol]
Solution Pen-injector, Subcutaneous:
Entuzity Kwikpen: 500 units/mL (3 mL) [contains metacresol]
Parenteral: Do not use if solution is viscous or cloudy; use only if clear and colorless.
SUBQ: Administer ~30 minutes before meals. Cold injections should be avoided. Administration is usually made into the subcutaneous fat of the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Per the manufacturer, Novolin regular insulin is not recommended for use in external SUBQ insulin infusion pump due to precipitation concerns.
U-100 regular insulin:
Vial: When mixing U-100 regular insulin with other insulin preparations, regular insulin should be drawn into the syringe first. While not preferred, regular insulin may be infused SUBQ by external insulin pump (eg, when rapid-acting insulin not available) (Ref); however, when used in an external pump, it is not recommended to be diluted with other solutions.
Prefilled pens: Novolin R FlexPen and Novolin R FlexPen ReliOn are available in a concentration of 100 units/mL. Devices are designed to display the actual insulin units administered (no dosage conversion needed) and will administer up to 60 units per injection in 1-unit increments. Prime the needle before each injection with 2 units of insulin (use a new needle for each injection); see manufacturer's labeling for specific procedure. Once primed, set dial to the appropriate dose, insert needle into clean skin, and activate device by holding the button down; continue to hold the button until the dose dial has returned to 0 units. After the insulin is injected, hold the needle in the skin for ≥6 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered. Do not rub the area. If dose is >60 units, >1 injection will be required; split dose and administer in multiple injections. Do not mix other insulin formulations with insulin regular contained in a prefilled pen.
U-500 regular insulin (concentrated): Concentrated U-500 regular insulin is indicated only in patients requiring >200 units/day of insulin. Do not dilute or mix U-500 regular insulin.
Vial: U -500 regular insulin vials are to be used only in conjunction with a dedicated U-500 insulin syringe; dosage conversion is not required with the U-500 syringe. Only in cases where the U-500 insulin syringe is not available, a U-100 insulin syringe or a tuberculin syringe may be necessary. When using a U-100 syringe or a tuberculin syringe to deliver Humulin R U-500 (from vial), a conversion step is required to ensure the correct amount of Humulin R U-500 is drawn up in the syringe. To avoid dosing errors when using a U-100 insulin syringe, the prescribed dose should be written in actual insulin units and as unit markings on the U-100 insulin syringe (eg, Humulin R U-500 50 units = 10 units on a U-100 insulin syringe). To avoid dosing errors when using a tuberculin syringe, the prescribed dose should be written in actual insulin units and as a volume (eg, Humulin R U-500 50 units = 0.1 mL on a tuberculin syringe).
Prefilled pen: Do not perform dose conversions when using the KwikPen; the dose window shows the number of units to be injected. The Humulin R KwikPen will administer up to 300 units per injection in 5-unit increments. Prime the needle before each injection with 5 units of insulin (use a new needle for each injection); see manufacturer's labeling for specific procedure. Once primed, set dial to the appropriate dose, insert needle into clean skin, and activate device by holding the button down; continue to hold the button until the dose dial has returned to 0 units. After the insulin is injected, hold the needle in the skin for 5 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered. Do not rub the area. If dose is >300 units, >1 injection will be required; split dose and administer in multiple injections. Do not transfer KwikPen insulin into a syringe for administration.
IM: U-100 regular insulin: May be administered IM in selected clinical situations; close monitoring of blood glucose and serum potassium as well as medical supervision is required. Do not administer U-500 regular insulin IM.
IV: U-100 regular insulin: Preferred insulin formulation approved for IV administration; requires close monitoring of blood glucose and serum potassium; appropriate medical supervision. Do not administer U-500 regular insulin or mixtures of insulin formulations intravenously.
Continuous IV Infusion: U-100 regular insulin: To minimize insulin adsorption to plastic IV tubing: Insulin loss will occur by adsorption to plastic (ie, PVC, polyethylene, polyolefin, polypropylene) IV containers and tubing (Ref). Therefore, flush IV tubing with a priming volume of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (Ref). Studies examining this issue in neonates suggest that flushing the IV tubing prior to administration reduces adsorption and provides improved and more predictable insulin delivery; however, the combination of flushing along with preconditioning (waiting a predefined time after flushing the IV line before infusing) provides the greatest reduction in insulin adsorption; wait times for preconditioning varied among studies from 20 to 60 minutes; flush volumes varied and were as high as 20 mL (Ref).
High-dose insulin therapy (for treating calcium channel blocker or beta-blocker toxicity): U-100 regular insulin: Administer as a continuous IV infusion. Additional precautions should be implemented to ensure accurate infusion pump settings, with particular attention to infusion concentration required (Ref). Refer to institution-specific protocols where appropriate.
Because of adsorption to plastic IV tubing or infusion bags, the actual amount of insulin being administered could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on the effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SUBQ dosing regimen (Ref); however, the transition to SUBQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy.
SUBQ administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. Regular insulin should be administered ~30 minutes before a meal. Cold injections should be avoided. SUBQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia.
U-100 regular insulin: When mixing U-100 regular insulin with other preparations of insulin, regular insulin should be drawn into syringe first.
FlexPen: Prime the needle before each injection with 2 units of insulin. Once injected, hold the needle in the skin for at least 6 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.
U-500 regular insulin (concentrated): Do not dilute or mix U-500 regular insulin.
Vials: U-500 regular insulin vials are to be used only in conjunction with a dedicated U-500 insulin syringe; dosage conversion is not required with the U-500 syringe. Only in cases where the U-500 insulin syringe is not available, a U-100 insulin syringe or a tuberculin syringe may be necessary. When using a U-100 syringe or a tuberculin syringe to deliver Humulin R U-500 (from vial), a conversion step is required to ensure the correct amount of Humulin R U-500 is drawn up in the syringe. To avoid dosing errors when using a U-100 insulin syringe, the prescribed dose should be written in actual insulin units and as unit markings on the U-100 insulin syringe (eg, Humulin R U-500 50 units = 10 units on a U-100 insulin syringe). To avoid dosing errors when using a tuberculin syringe, the prescribed dose should be written in actual insulin units and as a volume (eg, Humulin R U-500 50 units = 0.1 mL on a tuberculin syringe).
Humulin KwikPen (U-500): Do not perform dose conversions when using the KwikPen; the dose window shows the number of units to be injected. The KwikPen dials by 5-unit increments, resulting in delivery of doses in 5-unit increments. Do not transfer KwikPen insulin into a syringe for administration. Prime the needle before each injection with 5 units of insulin. Once the dose is injected, hold the needle in the skin for ~5 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.
Entuzity KwikPen (U-500) [Canadian product]: Do not perform dose conversions when using the KwikPen; the dose window shows the number of units to be injected. The KwikPen dials by 5-unit increments, resulting in delivery of doses in 5-unit increments. Do not transfer KwikPen insulin into a syringe for administration.
Continuous SUBQ insulin infusion: Novolin regular insulin (U-100) is not recommended for use in external SUBQ insulin infusion pump due to precipitation concerns (manufacturer labeling). Concentrated U-500 regular insulin is generally not recommended for use in an insulin pump but may be used in select patients under the supervision of an experienced provider (Ref).
IV administration: Do not administer concentrated U-500 regular insulin or mixtures of insulin formulations IV. Do not use if solution is viscous or cloudy; use only if clear and colorless. U-100 regular insulin may be administered IV with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Note: A 100 units/100 mL premixed solution is also available for IV infusion.
IV infusions: To minimize insulin adsorption to plastic IV tubing: Insulin loss will occur by adsorption to plastic (ie, PVC, polyethylene, polyolefin, polypropylene) IV containers and tubing (Ref). Therefore, flush the IV tubing with a priming infusion of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (Ref).
If insulin is required prior to the availability of the insulin infusion, regular insulin should be administered by IV push injection.
Because of insulin adsorption to plastic IV tubing or infusion bags, the actual amount of insulin being administered via IV infusion could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SUBQ dosing regimen (Ref); however, the transition to SUBQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy. In addition, SUBQ basal insulin should be administered ≥2 to 4 hours before discontinuing IV insulin infusion to prevent hyperglycemia (Ref).
IV Infusion: 0.1 unit/mL or 0.5 unit/mL
IV infusion: 0.1 unit/mL, 0.2 unit/mL, 0.5 unit/mL, or 1 unit/mL.
Humulin R U-100: Store unopened vials under refrigeration between 2°C and 8°C (36°F and 46°F) until expiration date or at room temperature ≤30°C (≤86°F) for 31 days; do not freeze and do not use if the vial has been frozen; keep away from heat and sunlight. Store in-use vials under refrigeration between 2°C and 8°C (36°F and 46°F) or at room temperature ≤30°C (≤86°F) and use within 31 days.
Humulin R U-500:
Vials: Store unopened vials under refrigeration between 2°C and 8°C (36°F and 46°F) until expiration date or at room temperature ≤30°C (≤86°F) for 40 days; do not shake; protect from heat and light; do not freeze and do not use if the vial has been frozen. Store in-use vials under refrigeration between 2°C and 8°C (36°F and 46°F) or at room temperature ≤30°C (≤86°F) and use within 40 days.
KwikPen: Store unopened prefilled pens under refrigeration between 2°C and 8°C (36°F and 46°F) until expiration date or at room temperature ≤30°C (≤86°F) for 28 days; protect from heat and light; do not freeze and do not use if the pen has been frozen. Store in-use prefilled pens at room temperature ≤30°C (≤86°F) and use within 28 days; do not refrigerate.
Myxredlin: Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze or shake. May be stored at room temperature (<25°C [<77°F]) for ≤30 days; do not return to refrigerator once stored at room temperature; discard after 30 days.
Novolin R:
Vials: Store unopened vials under refrigeration between 2°C and 8°C (36°F and 46°F) until expiration date or at room temperature ≤25°C (≤77°F) for 42 days; do not freeze; keep away from heat and sunlight. Store in-use vials at room temperature ≤25°C (≤77°F) and use within 42 days; do not refrigerate.
FlexPen: Store unopened prefilled pens under refrigeration between 2°C and 8°C (36°F and 46°F) until expiration date or at room temperature ≤30°C (≤86°F) for 28 days; do not use if frozen; keep away from heat and light. Store in-use prefilled pens at room temperature ≤30°C (≤86°F) and use within 28 days.
Canadian labeling (not in US labeling): All products: Store unopened vials, cartridges, and prefilled pens under refrigeration between 2°C and 8°C (36°F and 46°F) until expiration date; do not freeze; keep away from heat and sunlight. Store in-use Humulin vials, cartridges, and prefilled pens at room temperature <25°C (<77°F) and use within 4 weeks. Store in-use Novolin GE vials, cartridges, and prefilled pens at room temperature <25°C (<77°F) for vials or <30°C (<86°F) for prefilled pens/cartridges and use within 1 month; do not refrigerate. Store in-use Entuzity KwikPen prefilled pens at room temperature ≤30°C (≤86°F) and use within 4 weeks; do not refrigerate.
Diluted solution for SUBQ administration: Humulin R U-100: Diluted insulin solution may be stored at 30°C (86°F) for ≤14 days or at 5°C (41°F) for ≤28 days.
According to the manufacturer, do not store diluted insulin in a plastic syringe; store unused sterile diluent at room temperature; once in use, the sterile diluent vial should be used within 28 days (data on file [Eli Lilly 2018]).
For IV infusion: Note: A 100 units/100 mL premixed solution is also available for IV infusion.
Humulin R U-100: Stable for 48 hours at room temperature or for 48 hours under refrigeration followed by 48 hours at room temperature.
Novolin R: Stable for 24 hours at room temperature
Note: After dilution of 100 units of regular human insulin (product not specified) in 100 mL of 0.9% NaCl (PVC bag), the solution is stable under refrigeration between 2°C and 8°C (36°F to 46°F) for ≤336 hours (Rocchio 2013).
After dilution of 800 units of regular insulin (8 mL of a 100 units/mL solution) in 42 mL of 0.9% NaCl (PVC bag) to a final concentration of 16 units/mL, the solution is stable under refrigeration at 4°C (39°F) or at room temperature at 25°C (77°F) for 14 days (Laskey 2016).
Improvement of glycemic control in patients with diabetes mellitus (FDA approved in pediatric patients [age not specified] and adults); has also been used for treatment of diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), treatment of hyperkalemia (used in combination with glucose to cause intracellular shift of potassium and lower serum potassium levels), and treatment of calcium channel blocker or beta-blocker toxicity.
Note: Concentrated U-500 regular insulin is indicated only in patients requiring >200 units/day of insulin.
HumuLIN R may be confused with HumaLOG, Humira, HumuLIN 70/30, HumuLIN N, NovoLIN 70/30, NovoLIN R, NovoLOG
NovoLIN R may be confused with HumuLIN R, NovoLIN 70/30, NovoLIN N, NovoLOG
Insulin may be confused with influenza virus vaccine. Medication errors have occurred when insulin was inadvertently administered instead of influenza virus vaccine. These products are refrigerated and may be stored in close proximity to each other.
The Institute for Safe Medication Practices (ISMP) includes this medication (with special emphasis on U-500 insulin) among its list of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.
Beers Criteria: Insulin (short- or rapid-acting insulin products used for sliding scale) is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to higher risk of hypoglycemia associated with sliding scale insulin without improvements in hyperglycemia, regardless of care setting. Avoid insulin regimens that only use short- or rapid-acting insulins dosed based on current blood glucose levels in the absence of basal or long-acting insulin; recommendation does not apply to regimens containing basal or long-acting insulin (Beers Criteria [AGS 2023]).
Concentrated solutions (eg, U-500) should not be available in patient care areas. U-500 regular insulin should be stored, dispensed, and administered separately from U-100 regular insulin. U-500 insulin vials are to be used in conjunction only with a dedicated U-500 insulin syringe. Though no longer recommended by the manufacturer, in cases where the U-500 insulin syringe is not available, a U-100 insulin syringe or a tuberculin syringe may be used (conversion step required to ensure correct dose is drawn up). For patients who receive U-500 insulin in the hospital setting, highlighting the strength prominently on the patient's medical chart and medication record may help to reduce dispensing errors. For patients being discharged from the hospital and/or in the outpatient setting, a U-500 insulin syringe is available by prescription only and should be prescribed/dispensed in conjunction with U-500 insulin vials.
Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy
Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Chlorprothixene: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy
Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Monitor patients for hypoglycemia. Risk D: Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Risk D: Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Patients diagnosed with diabetes who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2022). Rapid acting insulin analogs are preferred over short acting regular insulin in patients planning to become pregnant (Blumer 2013).
Exogenous insulin bound to anti-insulin antibodies can be detected in cord blood (Menon 1990).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2022; Blumer 2013).
Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2022).
Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed (ACOG 190 2018; ACOG 201 2018; ADA 2022). Rapid acting insulin analogs are preferred over short acting regular insulin when treatment is needed during pregnancy due to improved outcomes and increased compliance (ACOG 198 2018; ACOG 201 2018; Blumer 2013). Regular insulin is used intravenously for glycemic control during labor.
Diabetes: Serum glucose, electrolytes, HbA1c (every 3 months; if patient is stable and meeting treatment goals, may only need twice-yearly testing; patients not stable on intensive therapy [eg, pregnancy] may need more frequent testing) (ADA 2020), renal function (at diagnosis and at least annually) (ADA [Chiang 2014]), hepatic function.
Diabetic ketoacidosis/hyperosmolar hyperglycemic state: Vital signs, arterial blood gases (initial), venous pH, CBC with differential, urinalysis, serum glucose, BUN, creatinine, electrolytes, calcium, magnesium, phosphate, anion gap, fluid status, blood β-hydroxybutyrate (BOHB) concentration; neurological observations; mental status (ISPAD [Wolfsdorf 2018]).
Hyperglycemia, neonatal: Monitor serum glucose 30 to 60 minutes after intermittent IV dose, initiation of continuous infusion, or rate change (Eichenwald 2017; Hemachandra 1999); must be closely monitored to avoid hypoglycemia and/or hypokalemia. Consult individual institutional policies and procedures.
Hyperkalemia: Serum potassium and glucose must be closely monitored to avoid hypoglycemia and/or hypokalemia.
Plasma Blood Glucose and HbA1c Goals for Diabetes Patients: Note: Postprandial blood glucose should be measured when there is a discrepancy between preprandial blood glucose concentrations and HbA1c values and to help assess glycemia for patients who receive basal/bolus or pump regimens. It is usually drawn 1 to 2 hours after starting a meal and is considered to be the "peak."
Children and Adolescents:
Blood glucose:
Type 1 diabetes:
Capillary glucose measurement: 70 to 180 mg/dL (SI: 3.9 to 10 mmol/L); tighter fasting target (ie, 70 to 144 mg/dL [SI: 3.9 to 8 mmol/L]) is recommended to attain HbA1c goals (ISPAD [de Bock 2022]).
Type 2 diabetes:
Fasting plasma glucose: 70 to 110 mg/dL (SI: 3.9 to 6.1 mmol/L) (ISPAD [Shah 2022]).
Postprandial glucose: 70 to 140 mg/dL (SI: 3.9 to 7.8 mmol/L) (ISPAD [Shah 2022]).
HbA1c: <7%; target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; lower targets may also be recommended when using insulin pumps and/or continuous glucose monitoring and during the "honeymoon" phase; less aggressive goals (<7.5% or <8%) may be appropriate in patients who cannot articulate symptoms of hypoglycemia, cannot check glucose frequently, have a history of severe hypoglycemia, have extensive comorbid conditions, or lack access to analog insulins, advanced insulin delivery technology, or continuous glucose monitoring (ADA 2023; ISPAD [de Bock 2022]).
Surgical patients (ISPAD [Kapellen 2022]):
Intraoperative: 90 to 180 mg/dL (SI: 5 to 10 mmol/L).
ICU, postsurgery: 140 to 180 mg/dL (SI: 7.8 to 10 mmol/L).
Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.
Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Insulin stimulates lipoprotein lipase synthesis and activity; this results in hydrolysis of triglycerides into free fatty acids and storage of free fatty acids in adipocytes, thereby reducing circulating triglyceride levels (Rawla 2018; Sadur 1982; Song 2019). In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.
Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Regular insulin has an identical structure to that of native human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin regular is a short-acting insulin analog.
The benefit of hyperinsulinemia-euglycemic therapy (HIET) in patients experiencing toxicity secondary to a calcium channel blocker (CCB) or beta blocker is not fully understood. It is hypothesized HIET improves myocyte glucose uptake and utilization; insulin may also act directly as a concentration-dependent inotrope. Exogenous insulin administration may help to overcome the hypoinsulinemia caused by CCB-induced blockage of L-type calcium channels in pancreatic beta cells (Krenz 2018).
Note: Onset and duration of hypoglycemic effects depend upon the route of administration (absorption and onset of action are more rapid after deeper IM injections than after SUBQ), site of injection (onset and duration are progressively slower with SUBQ injection into the abdomen, arm, buttock, or thigh respectively), volume and concentration of injection, and the preparation administered. Rate of absorption, onset, and duration of activity may be affected by exercise, presence of lipodystrophy, local blood supply, and/or temperature. Insulin regular is available in a U-100 (100 units/mL) formulation and a concentrated U-500 (500 units/mL) formulation, which have different pharmacodynamic/kinetic profiles.
Onset of action:
U-100 formulation: IV: ~10 to 21 minutes; SUBQ: ~30 minutes.
U-500 formulation: SUBQ: <15 minutes.
Peak effect:
U-100 formulation: IV infusion: ~5 hours; SUBQ: 1.5 to 3.5 hours.
U-500 formulation: SUBQ: 4 to 8 hours (dose dependent).
Duration:
U-100 formulation: IV infusion: 1.5 hours after stopping infusion; SUBQ: ~8 hours.
U-500 formulation: SUBQ: 13 to 24 hours.
Distribution: Vd: U-100 formulation: IV: 0.32 to 0.67 L/kg.
Bioavailability: U-100 formulation: SUBQ: 48% to 89%.
Half-life elimination:
U-100 formulation: IV: ~0.3 to 1 hour (dose dependent); SUBQ: 1.5 hours.
U-500 formulation: SUBQ: 4.5 hours.
Time to peak, plasma:
U-100 formulation: SUBQ: 0.5 to 2.5 hours.
U-500 formulation: SUBQ: 0.5 to 8 hours.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
