Note: Insulin lispro is a rapid-acting insulin analog available in a conventional formulation (eg, Admelog, Humalog) and an ultra-rapid formulation (Lyumjev), which differ in onset of action and administration instructions (Ref). Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose. When switching between insulin lispro products, continue with the same insulin dose.
Diabetes mellitus, type 1, treatment:
Note: Insulin lispro must be used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or via a continuous SUBQ insulin infusion device (U-100 only). The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.
General insulin dosing:
Initial TDD: SUBQ: ~0.4 to 0.5 units/kg/day (Ref); 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: 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 which 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: May be used if glycemic targets are not met despite adequately titrated basal insulin (eg, fasting glucose levels not 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: 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: 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 insulin lispro (Ref).
For hypoglycemia: SUBQ: 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).
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: 1 unit of insulin lispro per 10 to 15 g of carbohydrate prior to each bolus feeding; in patients receiving continuous feeds, administer every 4 hours based on the amount of carbohydrate administered over each 4-hour period (Ref).
Correctional: SUBQ: Administer correctional insulin as needed prior to each feeding (for bolus feeds) or every 4 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 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).
Diabetic ketoacidosis, mild to moderate, uncomplicated (alternative agent) (off-label use):
Note: SUBQ insulin lispro may be used as an alternative to IV regular insulin in patients in whom management of diabetic ketoacidosis (DKA) outside of a critical care area is appropriate; faster-acting insulin lispro products (eg, Lyumjev) have not been evaluated for this purpose. IV regular insulin (preferred over IV rapid-acting insulin analogs) should be used in patients with severe DKA, evidence of hyperosmolar hyperglycemic state (eg, altered mental status), persistent hypotension, or other critical illness, as well as during pregnancy (Ref). 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 (Kitabchi 2009). In patients with initial serum glucose <250 mg/dL, initiate dextrose-containing IV fluids at the time of insulin initiation (Ref). An example of a dosing regimen is as follows; refer to institutional protocols:
1-hour interval dosing: SUBQ: 0.3 units/kg once, followed by 0.1 units/kg every hour until blood glucose <250 mg/dL, then decrease to 0.05 units/kg every hour until resolution of ketoacidosis (Ref). May increase dose (eg, by double) if serum glucose does not decrease by ~50 to 75 mg/dL in the first hour (Ref).
2-hour interval dosing: SUBQ: 0.3 units/kg once, followed by 0.2 units/kg 1 hour later and then every 2 hours thereafter until blood glucose <250 mg/dL, then decrease to 0.1 units/kg every 2 hours until resolution of ketoacidosis. May increase dose (eg, by double) if serum glucose does not decrease by ~50 to 75 mg/dL in the first hour (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).
Correctional insulin:
Note: For use in addition to scheduled basal and nutritional insulin to achieve glycemic targets; prolonged use of correctional insulin without basal insulin is discouraged (Ref).
SUBQ: 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 4 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: 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: 1 unit of insulin lispro per 10 to 15 g of carbohydrate prior to each bolus feeding; in patients receiving continuous feeds, administer every 4 hours based on the amount of carbohydrate administered over each 4-hour period (Ref).
Patients receiving nutritional insulin prior to hospitalization: SUBQ: Continue the pre-hospitalization nutritional insulin dose; an empiric 25 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).
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.
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; monitor blood glucose closely.
(For additional information see "Insulin lispro (conventional and faster-acting): Pediatric drug information")
Insulin lispro is a rapid-acting insulin analog available in a conventional formulation (eg, Admelog, Humalog) and an ultra-rapid formulation (Lyumjev), which differ in onset of action, administration instructions, and approved ages for use.
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 dictates frequent monitoring and close medical supervision. Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.
Type 1 diabetes mellitus: Children and Adolescents: Note: Insulin lispro is generally used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or via a continuous SubQ insulin infusion pump (Humalog U-100 and Admelog U-100 only). 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 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 a 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).
Dosage 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 rapid-acting insulin (eg, aspart, glulisine, lispro) until after surgery and patient is able to eat unless it is needed to correct significant hyperglycemia and/or significant ketone (>0.1 mmol/mol) production is present.
Afternoon procedure: If allowed to eat breakfast, administer the usual dose of rapid-acting insulin (eg, aspart, glulisine, lispro) with breakfast.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to 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 changes related to surgery (ie, postoperative stress, medication changes, inactivity).
Type 2 diabetes mellitus: 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%, symptoms excluding acidosis) may include once-daily intermediate-acting insulin or basal insulin 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 (regular insulin or rapid-acting insulin) 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 doses or metformin monotherapy if able (Ref). Note: Patients who are ketotic or present with ketoacidosis require aggressive management.
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.
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.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Admelog: 100 units/mL (3 mL, 10 mL) [contains metacresol]
HumaLOG: 100 units/mL (3 mL, 10 mL) [contains metacresol, phenol]
Lyumjev: Insulin lispro-aabc 100 unit/mL (10 mL) [contains metacresol]
Generic: 100 units/mL (10 mL)
Solution, Subcutaneous:
HumaLOG: 100 units/mL (3 mL) [contains metacresol, phenol]
Solution Pen-injector, Subcutaneous:
Admelog SoloStar: 100 units/mL (3 mL) [contains metacresol]
HumaLOG Junior KwikPen: 100 units/mL (3 mL) [contains metacresol, phenol]
HumaLOG KwikPen: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]
HumaLOG Tempo Pen: 100 units/mL (3 mL) [contains metacresol, phenol]
Lyumjev KwikPen: Insulin lispro-aabc 100 unit/mL (3 mL); Insulin lispro-aabc 200 unit/mL (3 mL) [contains metacresol]
Lyumjev Tempo Pen: Insulin lispro-aabc 100 units/mL (3 mL) [contains metacresol]
Generic: 100 units/mL (3 mL)
Yes
Humalog Tempo Pen: The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.
Lyumjev Tempo Pen: The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Admelog: 100 units/mL (10 mL) [contains metacresol]
Solution Cartridge, Subcutaneous:
Admelog: 100 units/mL (3 mL) [contains metacresol]
Solution Pen-injector, Subcutaneous:
Admelog SoloStar: 100 units/mL (3 mL) [contains metacresol]
HumaLOG Junior KwikPen: 100 units/mL (3 mL) [contains metacresol]
HumaLOG KwikPen: 200 units/mL (3 mL) [contains metacresol]
Humalog Tempo Pen: FDA approved November 2019; anticipated availability is currently unknown. Information pertaining to this product within the monograph is pending revision. The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.
Use only if solution is clear and colorless; do not use if solution contains particulate matter or is colored.
SUBQ administration: 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.
Admelog: Administer within 15 minutes before or immediately after a meal. Do not mix with any other insulin. For Admelog SoloStar pen, prime the needle before each injection with 2 units of insulin. Once injected, hold the needle in the skin for ~10 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.
Humalog: Administer within 15 minutes before or immediately after a meal. Do not dilute or mix other insulins with insulin lispro contained in a cartridge or prefilled pen. Do not mix insulin lispro U-200 (200 units/mL) with any other insulin. May mix insulin lispro U-100 (100 units/mL) from a vial only with insulin NPH (do not mix with other types of insulin); insulin lispro should be drawn into syringe first; perform injection immediately. Prefilled pen devices are designed to dial doses in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen) or in 0.5-unit increments (U-100 Junior KwikPen). Do not perform dose conversion when using Humalog prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro U-200 to a syringe for administration. For Humalog prefilled pen devices, prime the needle before each injection with 2 units of insulin. Once 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.
Lyumjev: Administer at the start of a meal or within 20 minutes after starting a meal; routine postprandial use should be avoided due to reduced efficacy vs mealtime administration (Klaff 2020). Do not mix with any other insulin. Prefilled pen devices are designed to dial doses in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen) or in 0.5-unit increments (U-100 Junior KwikPen). Do not perform dose conversion when using prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro U-200 to a syringe for administration. For Lyumjev prefilled pen devices, prime the needle before each injection with 2 units of insulin. Once 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.
Continuous SUBQ insulin infusion administration: Insulin lispro U-100 (100 units/mL) may be administered via continuous SUBQ insulin infusion (CSII) device (ie, insulin pump); do not administer insulin lispro U-200 (200 units/mL) via a CSII device. Patients should be trained in the proper use of their CSII device and in intensive insulin therapy. Infusion sets and infusion set insertion sites should be changed every 3 days; rotate infusion sites. Insulin in reservoir should be changed at least every 7 days (Admelog, Humalog), 9 days (Lyumjev), or according to CSII device user manual (whichever is shorter). Do not dilute or mix other insulins with insulin lispro U-100 that is to be used in a CSII device.
IV administration: Insulin lispro U-100 (100 units/mL) may be administered IV with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Do not administer insulin lispro U-200 (200 units/mL) IV. Do not administer insulin mixtures IV.
IV infusions: To minimize adsorption to IV tubing: At low concentrations and flow rates, insulin lispro has been shown to adsorb to PVC IV bags and tubing (Ling 1999). 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).
Note: Also refer to institution-specific protocols where appropriate.
Because of insulin adsorption to 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. Transition to a protocol-driven basal/bolus insulin regimen should begin prior to stopping the IV infusion in order to avoid significant loss of glucose control (Ref).
Parenteral: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles.
SUBQ: Avoid cold injections. Administer into the subcutaneous fat of the thighs, arms, buttocks, or abdomen. Rotate injection sites within the same region to reduce the risk of 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.
Humalog: Administer within 15 minutes before or immediately after a meal. Do not dilute or mix other insulins with insulin lispro contained in a cartridge or prefilled pen. Do not mix insulin lispro U-200 (200 units/mL) with any other insulin.
Vial: Humalog U-100 (100 units/mL) from a vial may be mixed only with insulin NPH (do not mix with other types of insulin); insulin lispro should be drawn into syringe first. Use immediately after mixing.
Prefilled pens: Humalog prefilled pens are available in concentrations of 100 units/mL and 200 units/mL. Devices are designed to display the actual insulin units administered (no dosage conversion needed) and will administer up to 30 units per injection in 0.5-unit increments (U-100 Junior KwikPen) or up to 60 units per injection in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen). Do not transfer insulin lispro U-200 to a syringe for administration; markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia. For all Humalog prefilled pen devices, 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 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 >30 units (U-100 Junior KwikPen) or >60 units (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen), >1 injection will be required; split dose and administer in multiple injections.
Admelog: Admelog SoloStar prefilled pen will administer up to 80 units per injection in 1-unit increments. Prior to each injection, the needle must be primed 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 10 seconds after the dose dial has returned to 0 units to ensure the full dose has been administered. Do not rub the area. If dose is >80 units, >1 injection will be required; split dose and administer in multiple injections. Do not mix other insulin formulations with insulin lispro contained in a prefilled pen.
Continuous SUBQ insulin infusion (Insulin pump): Admelog and Humalog only: Insulin lispro U-100 (100 units/mL) may be administered via inulin pumps; do not administer insulin lispro U-200 (200 units/mL) via insulin pumps. Do not use if solution is viscous or cloudy; use only if clear and colorless. Patients should be trained in the proper use of their external insulin pump and in intensive insulin therapy. Infusion sets and infusion set insertion sites should be changed every 3 days; rotate infusion sites. Insulin in reservoir should be changed every 7 days or according to insulin pump user manual (whichever is shorter). Do not dilute or mix other insulin formulations with insulin lispro contained in an external insulin pump.
IV: Insulin lispro U-100 (100 units/mL) may be administered IV in selected clinical situations to control hyperglycemia. Closely monitor blood glucose and serum potassium; appropriate medical supervision is required. Further dilute with NS prior to administration. Do not administer insulin mixtures intravenously.
To minimize adsorption to IV tubing: At low concentrations and flow rates, insulin lispro has been shown to adsorb to PVC IV bags and tubing (Ref). Therefore, flush the 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). Also refer to institution-specific protocols where appropriate.
Because of adsorption, 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. Transition to a protocol-driven basal/bolus insulin regimen should begin prior to stopping the IV infusion in order to avoid significant loss of glucose control (Ref).
Diabetes mellitus, types 1 and 2, treatment: To improve glycemic control in pediatric patients (Lyumjev; ≥3 years of age [Admelog and Humalog]) and adults with type 1 diabetes mellitus; to improve glycemic control in adults with type 2 diabetes mellitus.
Diabetic ketoacidosis, mild to moderate, uncomplicated; Gestational diabetes mellitus; Hyperglycemia, hospitalized patients
HumaLOG may be confused with HumaLOG Mix 50/50, Humira, HumuLIN N, HumuLIN R, NovoLOG
Humapen Memoir (used with HumaLOG) may be confused with the Humira Pen
The Institute for Safe Medication Practices (ISMP) includes this medication 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 and strength 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 2019]).
Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics and may include concomitant basal insulin.
>10%:
Endocrine & metabolic: Severe hypoglycemia (≤14%)
Immunologic: Antibody development (19% to 33%)
Local: Infusion-site reaction (3% to 38%; includes infusion-site pain [16%])
Nervous system: Headache, pain
Respiratory: Cough, flu-like symptoms, nasopharyngitis (5% to 15%), pharyngitis, rhinitis
1% to 10%:
Dermatologic: Pruritus (≤1%)
Gastrointestinal: Abdominal pain, diarrhea, nausea
Local: Injection-site reaction (3% to 6%, may be secondary to excipient; including bruising at injection site, erythema at injection site, inflammation at injection site, injection-site pruritus, pain at injection site, rash at injection site)
Nervous system: Asthenia
Neuromuscular & skeletal: Myalgia (may be secondary to excipient)
Respiratory: Bronchitis, upper respiratory tract infection (1% to 7%)
<1%:
Cardiovascular: Peripheral edema
Hypersensitivity: Hypersensitivity reaction
Local: Hypertrophy at injection site, lipoatrophy at injection site
Frequency not defined: Endocrine & metabolic: Hypokalemia, weight gain
Postmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous)
Hypersensitivity to insulin lispro 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 or 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 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: Hypersensitivity reactions (serious, life-threatening and anaphylaxis) have occurred. If hypersensitivity reactions occur, discontinue administration and initiate supportive care measures.
• 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 (TZDs), 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. 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. Dosage requirements may be reduced, and patients may require more frequent dose adjustment and glucose monitoring.
Special populations:
• Hospitalized patients: Prolonged use of a sliding scale insulin regimen in the inpatient setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) 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:
• Prefilled pen devices: Do not perform dose conversion when using prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro from a prefilled pen to a syringe.
• Multiple-dose injection pens: According to the 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).
Other warnings/precautions:
• CSII administration: Insulin lispro U-100 (100 units/mL) may be administered via a CSII device; do not dilute or mix with other insulins. Rule out external pump failure if unexplained hyperglycemia or ketosis occurs; temporary SUBQ insulin administration may be required until the problem is identified and corrected. Insulin lispro U-200 (200 units/mL) is not indicated for use in a CSII device.
• IV administration: Insulin lispro U-100 (100 units/mL) may be administered IV in selected clinical situations to control hyperglycemia; close monitoring of blood glucose and serum potassium as well as medical supervision is required. Insulin lispro U-200 (200 units/mL) is not indicated for IV administration.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
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
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. 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
Patients with diabetes mellitus who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2022).
Insulin lispro is one of the preferred insulins for use in patients with diabetes mellitus planning to become pregnant (Blumer 2013).
Insulin lispro has not been shown to cross the placenta at standard clinical doses (Boskovic 2003; Holcberg 2004; Jovanovic 1999).
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 (ACOG 201 2018). 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). Insulin lispro is one of the preferred insulins for use in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013).
Both exogenous and endogenous insulin are present in breast milk (study not conducted with this preparation) (Whitmore 2012). Insulin is not systemically absorbed via breast milk but may provide local benefits to the infant GI tract (Anderson 2018).
Appropriate glycemic control is required for the establishment of lactation in patients with diabetes mellitus (Anderson 2018). Breastfeeding provides metabolic benefits to mothers with type 1, type 2, and gestational diabetes mellitus as well as their infants; therefore, breastfeeding is encouraged (ACOG 201 2018; ADA 2022; Blumer 2013). Breastfeeding also influences maternal glucose tolerance; close monitoring of patients treated with insulin is recommended as dose adjustments may be required (ADA 2022; Anderson 2018). A small snack before breastfeeding may help decrease the risk of hypoglycemia in patients with pregestational diabetes (ACOG 201 2018; Reader 2004). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Diabetes mellitus: Blood glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2022); electrolytes; renal function; hepatic function; weight.
Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 190 2018).
Hospitalized patients: In patients who are eating, monitor blood glucose before meals and at bedtime; in patients who are not eating or are receiving continuous enteral feeds, monitor blood glucose every 4 to 6 hours (ADA 2022; ES [Umpierrez 2012]). More frequent monitoring may be required in some cases (eg, recurrent hypoglycemia, changes in nutrition, medication changes affecting glycemic control) (ES [Umpierrez 2012]).
Critically ill patients receiving an IV insulin infusion: Monitor blood glucose every 1 to 2 hours; serum potassium (ADA 2022; SCCM [Jacobi 2012]; manufacturer’s labeling). Note: Arterial or venous whole blood sampling is recommended for patients in shock, on vasopressor therapy, or with severe edema, and when on a prolonged IV insulin infusion (SCCM [Jacobi 2012]).
HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2022; KDIGO 2020).
Diabetic ketoacidosis: Frequent monitoring (eg, every 1 to 4 hours) of serum electrolytes (eg, sodium, potassium, bicarbonate, phosphate), serum glucose, anion gap, venous pH, serum BUN, serum creatinine, serum osmolality, fluid status (eg, blood pressure, fluid intake/output, signs/symptoms of dehydration or fluid overload), anion gap, and mental status. Refer also to institutional protocols (Hirsch 2021; Kitabchi 2009).
Recommendations for glycemic control in patients with diabetes and/or hyperglycemia:
Nonpregnant adults (ADA 2022):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.
Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2022):
Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).
HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.
Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).
Pregnant patients:
HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2022):
Preconception (patients planning for pregnancy): <6.5%.
During pregnancy: <6% (if can be achieved without significant hypoglycemia) or <7% if needed to prevent hypoglycemia.
Capillary blood glucose: Note: Less stringent targets may be appropriate if goals cannot be achieved without causing significant hypoglycemia (ADA 2022).
Gestational diabetes mellitus (ACOG 190 2018; ADA 2022):
Fasting: <95 mg/dL.
Postprandial: <140 mg/dL (at 1 hour) or <120 mg/dL (at 2 hours).
Pregestational diabetes mellitus (type 1 or type 2) (ADA 2022 ):
Fasting: 70 to 95 mg/dL.
Postprandial: 110 to 140 mg/dL (at 1 hour) or 100 to 120 mg/dL (at 2 hours).
Hospitalized adult patients (ADA 2022): Target glucose range: 140 to 180 mg/dL (majority of critically ill and noncritically ill patients; <140 mg/dL may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia).
Perioperative care in adult patients (ADA 2022): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL.
Children and adolescents:
Preprandial glucose: 70 to 130 mg/dL (ISPAD [Dimeglio 2018]).
Postprandial glucose: 90 to 180 mg/dL (ISPAD [Dimeglio 2018]).
Bedtime/overnight glucose: 80 to 140 mg/dL (ISPAD [Dimeglio 2018]).
HbA1c: <7%; target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; 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, or have extensive comorbid conditions (ADA 2022; ISPAD [Dimeglio 2018]).
Surgical patients (ISPAD [Jefferies 2018]):
Intraoperative: 90 to 180 mg/dL.
ICU, postsurgery: 140 to 180 mg/dL.
Classification of hypoglycemia (ADA 2022):
Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
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. Insulin lispro differs from human insulin by containing a lysine and proline at positions B28 and B29, respectively, in comparison to the proline and lysine found at B28 and B29 in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin lispro is a rapid-acting insulin analog.
Note: Onset and duration of hypoglycemic effects depend upon the route of administration, 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 lispro is available in multiple formulations. Humalog and Admelog are highly similar (Kapitza 2017); Lyumjev formulation contains unique excipients (treprostinil and citrate) that facilitate more rapid SUBQ absorption (Leohr 2020; Linnebjerg 2020).
Onset of action: SUBQ:
Admelog: Similar onset to Humalog (Kapitza 2017).
Humalog: 31 minutes (patients with type 1 diabetes) (Linnebjerg 2020); 45 minutes (patients with type 2 diabetes) (Leohr 2020).
Lyumjev: ~15 to 17 minutes (manufacturer's labeling); 20.1 minutes (patients with type 1 diabetes) (Linnebjerg 2020); 32 minutes (patients with type 2 diabetes) (Leohr 2020).
Peak effect:
Admelog: ~2.1 hours.
Humalog: 2.4 to 2.8 hours.
Lyumjev: ~2 to 2.9 hours.
Duration: SUBQ:
Admelog: ~6.9 hours (patients with type 1 diabetes) (Kapitza 2017).
Humalog: ~5.7 to 6.6 hours (patients with type 1 diabetes) (Kapitza 2017; Linnebjerg 2020); ~6.7 hours (patients with type 2 diabetes) (Leohr 2020).
Lyumjev: ~4.6 to 7.3 hours (manufacturer's labeling); ~5 hours (patients with type 1 diabetes) (Linnebjerg 2020); ~6.4 hours (patients with type 2 diabetes) (Leohr 2020).
Distribution: Vd: IV: Humalog: 0.72 to 1.55 L/kg (inversely related to dose); Lyumjev: 34 L.
Bioavailability: SUBQ: Admelog, Humalog: 55% to 77%; Lyumjev: 65%.
Half-life elimination: Admelog, Humalog: 51 to 60 minutes; Lyumjev: 44 minutes.
Time to peak, plasma: SUBQ:
Admelog, Humalog: Median: ~50 minutes (Kapitza 2017; manufacturer's labeling [Admelog]); range: 30 to 90 minutes (manufacturer's labeling [Humalog]).
Lyumjev: 57 minutes; time to reach 50% of peak plasma concentration was 14 minutes shorter compared to Humalog in patients with type 1 diabetes (14.8 vs 29 minutes, respectively) (Linnebjerg 2020) and 11 minutes shorter compared to Humalog in patients with type 2 diabetes (18.6 vs 29.6 minutes respectively) (Leohr 2020).
Altered kidney function: Insulin clearance may be reduced in patients with impaired renal function.
Solution (Admelog Injection)
100 units/mL (per mL): $15.69
Solution (HumaLOG Injection)
100 units/mL (per mL): $32.96
Solution (Insulin Lispro Injection)
100 units/mL (per mL): $9.89
Solution (Lyumjev Injection)
100 units/mL (per mL): $32.96
Solution Cartridge (HumaLOG Subcutaneous)
100 units/mL (per mL): $40.84
Solution Pen-injector (Admelog SoloStar Subcutaneous)
100 units/mL (per mL): $15.15
Solution Pen-injector (HumaLOG Junior KwikPen Subcutaneous)
100 units/mL (per mL): $42.43
Solution Pen-injector (HumaLOG KwikPen Subcutaneous)
100 units/mL (per mL): $42.43
200 units/mL (per mL): $84.86
Solution Pen-injector (HumaLOG Tempo Pen Subcutaneous)
100 units/mL (per mL): $42.43
Solution Pen-injector (Insulin Lispro (1 Unit Dial) Subcutaneous)
100 units/mL (per mL): $12.73
Solution Pen-injector (Lyumjev KwikPen Subcutaneous)
100 units/mL (per mL): $42.43
200 units/mL (per mL): $84.86
Solution Pen-injector (Lyumjev Tempo Pen Subcutaneous)
100 units/mL (per mL): $42.43
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