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Insulin regular: Drug information

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Contributor Disclosures
For additional information see "Insulin regular: Patient drug information" and "Insulin regular: Pediatric drug
information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US
HumuLIN R U-500 (CONCENTRATED); HumuLIN R U-500 KwikPen; HumuLIN R [OTC]; Myxredlin;
NovoLIN R FlexPen ReliOn [OTC]; NovoLIN R FlexPen [OTC]; NovoLIN R ReliOn [OTC]; NovoLIN R
[OTC]

Brand Names: Canada

Entuzity Kwikpen; HumuLIN R; HumuLIN R KwikPen; Myxredlin; NovoLIN GE Toronto; NovoLIN
GE Toronto Penfill

Pharmacologic Category
Insulin, Short-Acting

Dosing: Adult
Dosage guidance:

Dosage form information: Regular insulin U-100 is not interchangeable with concentrated
U-500 regular insulin.

Clinical considerations: 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.

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Calcium channel blocker or beta-blocker overdose/toxicity 

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 

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 

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).

Diabetes mellitus, patients receiving enteral feedings 

Diabetes mellitus, patients 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).

Diabetes mellitus, patients receiving parenteral feedings 

Diabetes mellitus, patients 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).

Diabetes mellitus, patients undergoing surgery and using an insulin pump 

Diabetes mellitus, patients 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 

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 

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 

Hyperglycemia, hospitalized patients (off-label use):

Note: For use in patients with persistent hyperglycemia (eg, blood glucose ≥180
mg/dL on two occasions) with or without a history of diabetes. Individualize
glycemic targets depending on clinical status; 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 (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 

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.

Dosing: Kidney Impairment: Adult

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

Dosing: Liver Impairment: Adult

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.

Dosing: Older Adult

Refer to adult dosing; avoid this agent in the absence of basal or long-acting insulin (Ref).

Dosing: Pediatric
(For additional information see "Insulin regular: Pediatric drug information")

Dosage guidance:

Clinical considerations: 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.
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Diabetes mellitus, type 1 

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 

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 

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 

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 

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 

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Liver Impairment: Pediatric

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.

Adverse Reactions
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
Contraindications
Hypersensitivity to regular insulin or any component of the formulation; during episodes of
hypoglycemia.

Warnings/Precautions
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:
- Presurgical assessment of the indication for use, symptoms, and goals of therapy
should be documented to enable postsurgical assessment. Insulin therapy is the
preferred treatment for diabetes in the early postoperative period; however, due to
wide interpatient variability close monitoring and dosage adjustments are required
to maintain target blood glucose levels and avoid hypoglycemia
(AACE/ASMBS/OMA/ASA [Mechanick 2020]). Studies found that prior to discharge
persons with type 1 diabetes required an average insulin dose reduction of 31% to
50% and patients with type 2 diabetes required a 61% to 87% dose reduction
(Cruijsen 2014; Diemer 2017; Kassel 2022; Middelbeek 2014; Vilarrasa 2017;
Wirunsawanya 2021). Furthermore, 1 year following surgery 60% of persons with
type 2 diabetes were in remission and able to discontinue insulin therapy
(Ardestani 2015; Arterburn 2013; Buchwald 2009; Schauer 2003; Varban 2022).

- DPP4 inhibitors, glucagon-like peptide-1 agonists, insulin, and metformin are

preferred for outpatient glucose management following bariatric surgery
(AACE/ASMBS/OMA/ASA [Mechanick 2020]). Consider alternatives to insulin for
glucose management in type 2 diabetes due to the risk of hypoglycemia and
weight gain associated with long-term insulin therapy (AACE/ASMBS/OMA/ASA
[Mechanick 2020]; Apovian 2015). Monitor and adjust the insulin dose for
hypoglycemia, hyperglycemia, or weight gain in persons requiring insulin,
including persons with type 1 diabetes.

• 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 2023).

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 2023). 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.

Dosage Forms: US
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]

Generic Equivalent Available: US

No

Pricing: US
Solution (HumuLIN R Injection)

100 units/mL (per mL): $5.35

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): $5.78

Solution (NovoLIN R ReliOn Injection)

100 units/mL (per mL): $5.78

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): $7.29

Solution Pen-injector (NovoLIN R FlexPen ReliOn Injection)

100 units/mL (per mL): $7.29

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.

Dosage Forms: Canada

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, Intravenous:

Myxredlin: 100 units/100 mL in NaCl 0.9% (100 mL)

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]

Administration: Adult
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).

Administration: Pediatric
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.

Usual Infusion Concentrations: Adult

IV infusion: 100 units in 100 mL (concentration: 1 unit/mL) of NS

Usual Infusion Concentrations: Pediatric

IV infusion: 0.1 unit/mL, 0.2 unit/mL, 0.5 unit/mL, or 1 unit/mL.

Use: Labeled Indications

Diabetes mellitus, types 1 and 2, treatment: Treatment of type 1 diabetes mellitus and type 2
diabetes mellitus to improve glycemic control.

Note: Concentrated U-500 regular insulin is indicated only in patients requiring more than 200
units of insulin per day.
Use: Off-Label: Adult
Cadaveric organ recovery (hormonal resuscitation); Calcium channel blocker or beta-blocker
overdose/toxicity; Diabetic ketoacidosis; Gestational diabetes mellitus; Hyperglycemia,
hospitalized patients; Hyperkalemia, severe/emergent; Hyperosmolar hyperglycemic state

Medication Safety Issues

Collapse All

Sound-alike/look-alike issues: 

HumuLIN R may be confused with HumaLOG, Humira, HumuLIN 70/30, HumuLIN N,

NovoLIN 70/30, NovoLIN R, NovoLOG

HumuLIN R U-500 may be confused with Humulin R U-100

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.

High alert medication: 

The Institute for Safe Medication Practices (ISMP) includes this medication among its
list of drug classes (insulins, all formulations and strengths, SUBQ, IV; with
special emphasis on U-500 insulin) which have a heightened risk of causing
significant patient harm when used in error (High-Alert Medications in Acute
Care, Community/Ambulatory Care, and Long-Term Care Settings). Due to the
number of insulin preparations, it is essential to identify/clarify the type of
insulin to be used.

Older Adult: High-Risk Medication: 

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]).

Administration issues: 

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.

Other safety concerns: 

Cross-contamination may occur if insulin pens are shared among multiple patients.
Steps should be taken to prohibit sharing of insulin pens.

Metabolism/Transport Effects
None known.

Drug Interactions
(For additional information: Launch drug interactions program)

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 drug interactions program by clicking on the “Launch drug
interactions program” link above.
Alpha-Glucosidase Inhibitors: May increase hypoglycemic effects of Insulin. 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 increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects.
Risk C: Monitor

Antidiabetic Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents.

Risk C: Monitor

Beta-Blockers (Beta1 Selective): May increase adverse/toxic effects of Antidiabetic Agents.

Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents.
Risk C: Monitor

Beta-Blockers (Nonselective): May increase hypoglycemic effects of Insulin. Beta-Blockers

(Nonselective) may decrease therapeutic effects of Insulin. Risk C: Monitor

Bortezomib: May increase therapeutic effects of Antidiabetic Agents. Bortezomib may decrease
therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Chlorprothixene: May increase hypoglycemic effects of Insulin. Risk C: Monitor

Clarithromycin: May increase hypoglycemic effects of Insulin. Risk C: Monitor

Dipeptidyl Peptidase-IV Inhibitors: May increase hypoglycemic effects of Insulin. 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 increase hypoglycemic effects of Antidiabetic Agents.
Risk C: Monitor

Edetate CALCIUM Disodium: May increase hypoglycemic effects of Insulin. Risk C: Monitor

Etilefrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Glucagon-Like Peptide-1 Agonists: May increase hypoglycemic effects of Insulin. 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 increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Herbal Products with Glucose Lowering Effects: May increase hypoglycemic effects of
Hypoglycemia-Associated Agents. Risk C: Monitor

Hyperglycemia-Associated Agents: May decrease therapeutic effects of Antidiabetic Agents. Risk

C: Monitor

Hypoglycemia-Associated Agents: Antidiabetic Agents may increase hypoglycemic effects of

Hypoglycemia-Associated Agents. Risk C: Monitor

Hypoglycemia-Associated Agents: May increase hypoglycemic effects of Hypoglycemia-

Associated Agents. Risk C: Monitor

Liraglutide: May increase hypoglycemic effects of Insulin. 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: Coadministration of Insulin and Macimorelin may alter diagnostic results. Risk X:
Avoid

Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk
C: Monitor

Metreleptin: May increase hypoglycemic effects of Insulin. 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 increase hypoglycemic effects of Agents with Blood
Glucose Lowering Effects. Risk C: Monitor

Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering
Effects. Risk C: Monitor

Pioglitazone: May increase adverse/toxic effects of Insulin. 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 increase hypoglycemic effects of Insulin. 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 increase hypoglycemic effects of Agents with Blood Glucose Lowering
Effects. Risk C: Monitor

Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects.
Quinolones may decrease therapeutic effects 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

Reproterol: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Ritodrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Rosiglitazone: Insulin may increase adverse/toxic effects of Rosiglitazone. Specifically, the risk of
fluid retention, heart failure, and hypoglycemia may be increased with this combination.
Risk X: Avoid

Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects.
Risk C: Monitor

Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood
Glucose Lowering Effects. Risk C: Monitor

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May increase hypoglycemic effects of

Insulin. 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 decrease therapeutic effects of Antidiabetic Agents.
Risk C: Monitor

Reproductive Considerations
Patients diagnosed with diabetes who wish to conceive should use adequate contraception until
glycemic control is achieved (ADA 2023). Rapid acting insulin analogs are preferred over short
acting regular insulin in patients planning to become pregnant (Blumer 2013).

Pregnancy Considerations
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 2023; 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 2023).

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 2023). 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.

Breastfeeding Considerations
Both exogenous and endogenous insulin are present in breast milk (study not conducted with
this preparation) (Whitmore 2012).

Adverse events have not been reported in breastfeeding infants following maternal use of
regular insulin for injection. 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 2023; Blumer 2013). Breastfeeding also
influences maternal glucose tolerance; close monitoring of patients treated with insulin is
recommended as dose adjustments may be required (ADA 2023; 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.

Dietary Considerations
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral
part of therapy.

Monitoring Parameters
Calcium channel blocker or beta-blocker overdose/toxicity (off-label use): Monitor blood glucose
levels every 15 to 60 minutes, with frequent attention to blood glucose levels during the
first hour of therapy. Serum electrolytes, including potassium, should be measured hourly
until patient is stable, then monitor serum potassium levels every 1 to 2 hours and serum
electrolyte measurement every 4 to 6 hours once stable. Consider serial ECG monitoring
(Engebretsen 2011; Krenz 2018).

Diabetes mellitus and hyperglycemia: Blood glucose (individualize frequency based on

treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2023);
electrolytes; renal function; hepatic function; weight.

Gestational diabetes mellitus: Blood glucose 4 times daily (one fasting and three
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 2023; 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 at least every 0.5
to 2 hours, with more frequent monitoring if glucose levels are unstable; serum
potassium (ADA 2023; SCCM [Honarmand 2024]; manufacturer's labeling). Refer also to
institutional protocols. Note: Arterial or venous whole blood sampling should be
prioritized over point-of-care glucose testing (SCCM [Honarmand 2024]).

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 2023; KDIGO 2020).

Diabetic ketoacidosis or hyperosmolar hyperglycemic state: Frequent monitoring (eg, every 1 to

4 hours) of serum electrolytes (eg, sodium, potassium, bicarbonate, phosphate), serum
glucose, anion gap, venous pH (for DKA), 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 2022;
Kitabchi 2009).

Hyperkalemia: Serum potassium and glucose must be closely monitored to avoid hypokalemia,
rebound hyperkalemia, and hypoglycemia.

Reference Range
Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults (AACE [Samson 2023]; ADA 2023):

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 (SI: 4.4 to 7.2 mmol/L) (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 (SI:
<10 mmol/L) (more or less stringent goals may be appropriate based on patient-
specific characteristics).

Older adults (≥65 years of age) (ADA 2023):

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% (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 (SI: 4.4 to 7.2 mmol/L) (healthy);
90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180
mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).

Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100
to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200
mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).

Pregnant patients:

HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2023):

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 2023).

Gestational diabetes mellitus (ACOG 190 2018; ADA 2023):

Fasting: <95 mg/dL (SI: <5.3 mmol/L).

Postprandial: <140 mg/dL (SI: <7.8 mmol/L) (at 1 hour) or <120 mg/dL (SI: <6.7
mmol/L) (at 2 hours).

Pregestational diabetes mellitus (type 1 or type 2) (ADA 2023 ):

Fasting: 70 to 95 mg/dL (SI: 3.9 to 5.3 mmol/L).

Postprandial: 110 to 140 mg/dL (SI: 6.1 to 7.8 mmol/L) (at 1 hour) or 100 to 120
mg/dL (SI: 5.6 to 6.7 mmol/L) (at 2 hours).

Perioperative care in adult patients (ADA 2023): Target glucose range during perioperative
period: Consider targeting 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L).

Children and Adolescents:

Preprandial glucose: 70 to 130 mg/dL (SI: 3.9 to 7.2 mmol/L) (ISPAD [Dimeglio 2018]).

Postprandial glucose: 90 to 180 mg/dL (SI: 5 to 10 mmol/L) (ISPAD [Dimeglio 2018]).

Bedtime/overnight glucose: 80 to 140 mg/dL (SI: 4.4 to 7.8 mmol/L) (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 2023; ISPAD
[Dimeglio 2018]).

Surgical patients (ISPAD [Jefferies 2018]):

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).

Recommendations for hospitalized adult patients with hyperglycemia:

Critically ill adult patients: Target glucose range: 140 to 200 mg/dL (SI: 7.8 to 11.1 mmol/L) is
appropriate for most patients; may consider a lower target range (eg, 110 to 140 mg/dL
[SI: 6.1 to 7.8 mmol/L]) if it can be achieved with a low risk of hypoglycemia. Refer also
to institutional protocols (SCCM [Honarmand 2024]).

Noncritically ill adult patients: Target glucose range: 140 to 180 mg/dL (SI: 7.8 to 10 mmol/L);
<140 mg/dL (SI: <7.8 mmol/L) may be appropriate for selected patients, if it can be
achieved without excessive hypoglycemia (ADA 2023).

Classification of hypoglycemia (ADA 2023):

Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting
carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL (SI: <3 mmol/L); 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.

Mechanism of Action
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).

Pharmacokinetics (Adult Data Unless Noted)

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.

Brand Names: International

International Brand Names by Country 
For country code abbreviations ( show table)

(AE) United Arab Emirates: Actrapid hm | Humulin regular | Jusline R; (AR) Argentina: Actrapid hm |
Densulin isofan | Densulin regular | Humulin r | Insulina Densulin R | Insulina Humulin R | Insuman
r | Novolin r; (AT) Austria: Actrapid | Huminsulin normal | Insulin hm actrapid | Insuman rapid; (AU)
Australia: Actrapid | Actrapid hm | Humulin r; (BD) Bangladesh: Actrapid flexpen | Ansulin R |
Diasulin n | Diasulin r | Humulin r | Insulet n | Insulet r | Insulin actrapid hm | Insuman rapid |
Mysulin r; (BE) Belgium: Actrapid | Humuline regular | Insuman rapid; (BF) Burkina Faso: Insulet
rapide | Insuman rapid; (BG) Bulgaria: Actrapid hm | Actrapid hm novolet | Actrapid novolet |
Humulin r | Insuman rapid; (BR) Brazil: Bahiafarma insulina humana r | Biohulin regular | Humulin r |
Insuman r | Novolin r | Wosulin r; (CH) Switzerland: Actrapid hm | Actrapid novolet; (CI) Côte d'Ivoire:
Insuman rapid; (CL) Chile: Actrapid hm | Humulin r | Insuman; (CN) China: Actrapid | Biosynthetic
Human Insulin | Gan shu lin r | Humulin r | Novolin r; (CO) Colombia: Actrapid hm | Gansulin r |
Humulin c | Humulin r | Insugen r | Insulex r | Insuman r; (CZ) Czech Republic: Actrapid hm |
Actrapid innolet | Actrapid novolet | Humulin r | Insulin-HM R | Insuman rapid | Velosulin HM; (DE)
Germany: Actrapid | Actrapid flexpen | Actrapid novolet | Berlinsulin h normal | Huma ject normal |
Huminsulin normal | Humulin normal | Insulin B. Braun ratiopharm rapid | Insuman rapid; (DO)
Dominican Republic: Humulin regular | Insuman r | Novolin r | Recomulin r; (EC) Ecuador: Actrapid |
Humulin r | Insuman r | Novolin r; (EE) Estonia: Actrapid | Actrapid hm | Humaject R | Humulin r |
Insuman rapid | Isuhuman rapid; (EG) Egypt: Actrapid hm | Humulin regular | Insulin h r | Insuman
rapid; (ES) Spain: Actrapid | Actrapid innolet | Actrapid novolet | Humaplus regular | Humulina
regular; (ET) Ethiopia: Actapid | Biosynthetic Human Insulin | Jusline R; (FI) Finland: Actrapid |
Humulin regular | Insuman rapid; (FR) France: Actrapid hm | Actrapid novolet | Humulin regular |
Insuman rapid | Umuline rapide | Velosuline hm; (GB) United Kingdom: Actrapid | Actrapid novolet |
Humulin s | Insuman rapid | Pur in Neutral | Velosulin; (GR) Greece: Actrapid | Actrapid novolet |
Humulin regular | Insulin actrapid hm | Insuman rapid | Velosulin HM; (HK) Hong Kong: Actrapid hm
| Humulin r; (HR) Croatia: Actrapid innolet; (HU) Hungary: Actrapid | Actrapid novolet | Humulin r |
Ins actrapid hm | Insulin actrapid hm(ge) | Insuman rapid; (ID) Indonesia: Actrapid hm | Actrapid
novolet | Humulin r | Insuman rapid; (IE) Ireland: Actrapid | Humulin r | Humulin s | Insuman; (IL)
Israel: Actrapid | Humulin r; (IN) India: Actrapid flexpen | Actrapid hm | Actrapid novolet | Humaject R
| Human actrapid | Human Insunorm | Human monosulin | Human rapidica | Human-fastact |
Humarap | Huminsulin-r | Insugen r | Insuman rapid | Recosulin-r | Wosulin r; (IT) Italy: Actrapid |
Bio insulin r | Humulin r | Insuman rapid; (JO) Jordan: Actrapid hm | Gensulin r | Humulin r; (JP)
Japan: Actrapid human | Humacart r | Humulin r | Innolet r | Novolin r | Velosulin; (KE) Kenya:
Actrapid | Humodar c25 | Humulin r | Jusline R; (KR) Korea, Republic of: Actrapid hm | Humaject R |
Humulin r | Novolet r | Novolin r | Velosulin Human; (KW) Kuwait: Actrapid hm | Actrapid novolet |
Humulin regular; (LB) Lebanon: Actrapid | Humulin regular | Insuman rapid | Velosulin HM; (LT)
Lithuania: Actrapid hm | Biogulin | Humulin r | Insuman rapid; (LU) Luxembourg: Actrapid |
Humaject Regular | Humuline regular | Velosuline hm; (LV) Latvia: Actrapid hm | Biogulin | Humulin r
| Insuman rapid; (MA) Morocco: Insulet r | Insulet rapide | Umuline rapide; (MX) Mexico: Humulin r |
Insulex r | Insuman r | Novolin r | Wozulim r; (MY) Malaysia: Actrapid flexpen | Actrapid hm |
Actrapid novolet | Humulin r; (NL) Netherlands: Actrapid | Actrapid flexpen | Actrapid novolet |
Humuline regular | Inpremzia | Insuman rapid | Velosulin; (NO) Norway: Actrapid | H-tronin |
Humulin r | Humulin regular | Insuman rapid; (NZ) New Zealand: Actrapid | Humulin r; (PE) Peru:
Actrapid hm | Humulin c | Humulin r | Insuman r; (PH) Philippines: Actrapid hm | Actrapid novolet |
Glysolin r | Humulin r | Insulyf r | Insuman rapid | Jusline R | Wosulin r; (PK) Pakistan: Actrapid hm |
Dongsulin R | Humulin regular | Innogen R | Insuget R | Insuman rapid | Zansulin regular; (PL)
Poland: Actrapid hm novolet | Gensulin r | Humulin r | Insuman rapid; (PR) Puerto Rico: Humulin r |
Myxredlin | Novolin r | Novolin r innolet | Relion/Novolin R | Velosulin rdna br; (PT) Portugal: Actrapid
| Humulin regular | Insulina actrapid hm | Insuman rapid; (PY) Paraguay: Actrapid hm | Humulin r |
Insubest r | Insuman r | Sulina r; (QA) Qatar: Actrapid | Actrapid Penfill | Humulin R | Insuman Rapid;
(RO) Romania: Humulin r | Insuman rapid; (RU) Russian Federation: Actrapid hm | Berlinsulin h
normal | Biogulin | Biosulin r | Gensulin r | Humodar r | Humulin r | Humulin regular | Ins actrapid
hm | Ins actrapid nm | Insuman rapid | Insuman rapid gt | Rosinsulin p | Wozulim r; (SA) Saudi
Arabia: Actrapid hm | Humulin regular; (SE) Sweden: Actrapid | Actrapid novolet | Insuman rapid |
Insuman Rapid SoloStar; (SG) Singapore: Actrapid hm | Actrapid novolet | Humulin r; (SI) Slovenia:
Actrapid hm | Humulin r; (SK) Slovakia: Actrapid hm | Humulin r | Insulin-HM R | Insuman rapid; (SR)
Suriname: Humulin r | Insugen r; (TH) Thailand: Actrapid hm | Biosulin r | Gensulin r | Humulin r |
Winsulin r; (TN) Tunisia: Actrapid | Insuline actrapid hm | Insuman rapid | Jusline R; (TR) Turkey:
Actrapid hm | Actrapid novolet | Humulin regular | Insulin Protaphan HM; (TW) Taiwan: Actrapid hm |
Humulin r | Insulin Regular hm | Velosulin | Velosulin HM; (UA) Ukraine: Actrapid flexpen | Actrapid
hm | Gensulin r | Humulin regular | Insular active | Insuman rapid; (UG) Uganda: Actrapid | Actrapid
flexpen | Biosulin r | Gensulin r | Humulin regular | Insugen r | Insuman rapid | Wosulin r; (UY)
Uruguay: Actrapid hm | Humulin r | Insubest r | Insuman r | Wosulin r; (VE) Venezuela, Bolivarian
Republic of: Humulin c | Humulin r | Insulex r | Insuman r; (ZA) South Africa: Actrapid | Biosulin r |
Humaject R | Humulin r

Use of UpToDate is subject to the Terms of Use.

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