Version July 2025
Dosage guidance:
Clinical considerations: Insulin icodec is a basal insulin. Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose.
Diabetes mellitus, type 1, treatment:
Note: Insulin icodec must be used concomitantly with rapid- or short-acting insulins (ie, multiple daily injections regimen). Insulin icodec has not been studied in patients with type 1 diabetes not previously on a basal-bolus regimen.
Conversion from other basal insulin to insulin icodec:
Initial: SUBQ: Multiply the previous daily basal insulin dose by 7 and round to the nearest 10 units (eg, a daily basal insulin dose of 35 units corresponds to a weekly insulin icodec dose of 250 units). Administer first insulin icodec dose on the day following the last dose of previous basal insulin and administer subsequent doses once weekly.
Note: Select patients may benefit from a 50% higher initial dose (depending on glycemic control and hypoglycemia history) for the first dose only. In these patients, multiply previous daily basal insulin dose by 10.5 and round to the nearest 10 units (eg, a daily basal insulin dose of 35 units corresponds to a one-time insulin icodec dose of 370 units). Subsequent once-weekly doses are determined by multiplying the previous daily basal insulin dose by 7 and rounding to the nearest 10 units.
Dosage adjustment for glycemic control: Increase or decrease weekly dose (eg, in 20-unit increments every 1 to 2 weeks) to maintain glucose in target range (Ref).
Diabetes mellitus, type 2, treatment:
Note: Preferred in patients with symptomatic hyperglycemia (eg, weight loss, polydipsia, polyuria) or ketonuria; may also be used in patients with severe hyperglycemia (eg, fasting glucose >250 mg/dL, random glucose consistently >300 mg/dL, HbA1c >9%), or if glycemic goals are not met despite adequately titrated noninsulin agents (Ref). Consider discontinuation or a dose reduction of sulfonylureas and thiazolidinediones when initiating basal insulin therapy (Ref).
Patients not currently on basal insulin:
Initial: SUBQ: 70 units once weekly.
Dosage adjustment for glycemic control: Increase or decrease weekly dose (eg, in 20-unit increments every 1 to 2 weeks) to maintain glucose in target range (Ref).
Conversion from other basal insulin to insulin icodec:
Initial: SUBQ: Multiply the previous daily basal insulin dose by 7 and round to the nearest 10 units (eg, a daily basal insulin dose of 35 units corresponds to a weekly insulin icodec dose of 250 units). Administer first insulin icodec dose on the day following the last dose of previous basal insulin and administer subsequent doses once weekly.
Note: Select patients may benefit from a 50% higher initial dose (depending on glycemic control and hypoglycemia history) for the first dose only. In these patients, multiply previous daily basal insulin dose by 10.5 and round to the nearest 10 units (eg, a daily basal insulin dose of 35 units corresponds to a one-time insulin icodec dose of 370 units). Subsequent once-weekly doses are determined by multiplying the previous daily basal insulin dose by 7 and rounding to the nearest 10 units.
Dosage adjustment for glycemic control: Increase or decrease weekly dose (eg, in 20-unit increments every 1 to 2 weeks) to maintain glucose in target range (Ref).
Missed doses:
If 3 or fewer days until next regularly scheduled dose: Administer missed dose as soon as possible; reset weekly dosing schedule to start 1 week later.
If 4 or more days until next regularly scheduled dose: Administer missed dose as soon as possible; continue current weekly dosing schedule.
There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
Refer to adult dosing; consider conservative initial and maintenance doses as well as dosage adjustments to avoid hypoglycemia.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Severe hypoglycemia (9% to 85%)
Immunologic: Antibody development (70% to 79%; neutralizing: 13%)
1% to 10%:
Cardiovascular: Hypertension (2%), peripheral edema (≤1%), premature ventricular contractions (1%)
Dermatologic: Alopecia (1%), dermatitis (1%), skin rash (1%)
Endocrine & metabolic: Dyslipidemia (1%), weight gain (1%)
Gastrointestinal: Diarrhea (2% to 5%), gastroenteritis (1% to 2%), nausea (2%), upper abdominal pain (1%), vomiting (1% to 2%)
Genitourinary: Cystitis (1%), urinary tract infection (2%)
Hematologic & oncologic: Anemia (1%)
Hepatic: Liver steatosis (1%)
Infection: Influenza (2%)
Local: Injection-site reaction (2%)
Nervous system: Dizziness (2%), falling (1%), fatigue (1% to 2%), headache (3% to 5%), malaise (1%), pain (1%)
Neuromuscular & skeletal: Back pain (3%), limb pain (2%), muscle spasm (1%), osteoarthritis (1%), sprain (1%)
Ophthalmic: Cataract (1%), conjunctivitis (1%), macular edema (1%)
Respiratory: Bronchitis (1%), cough (1%), flu-like symptoms (1%), nasopharyngitis (4%), oropharyngeal pain (1% to 2%), pharyngitis (2%), respiratory system disorder (1%), sinusitis (2%), upper respiratory tract infection (3%), viral respiratory tract infection (1%)
Miscellaneous: Fever (3%)
<1%: Hypersensitivity: Hypersensitivity reaction
Hypersensitivity to insulin icodec or any component of the formulation; during episodes of hypoglycemia.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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; the maximal glucose-lowering effect of insulin icodec occurs during days 2 to 4 following each weekly injection. 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, insulin icodec) 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 allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy.
• 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 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 2019). Insulin secretion and sensitivity may be partially or completely restored early after these procedures (gastric bypass is most effective, followed by sleeve, and finally band) (Korner 2009; Peterli 2012). Monitoring of hospital insulin requirements is recommended to guide discharge insulin dose. 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 beta-cell failure (fasting C-peptide <0.3 nmol/L) (Cruijsen 2014).
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones, may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Diabetic ketoacidosis: Should not be used in patients with diabetic ketoacidosis; use of a rapid-acting or short-acting insulin is required.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.
• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.
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 2024).
Dosage form specific issues:
• 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 2024).
Other warnings/precautions:
• Administration: Insulin icodec is a clear solution, but it is NOT intended for IV or IM administration or via an insulin pump.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Awiqli: Insulin icodec-f214 700 units/mL (1 mL, 1.5 mL, 3 mL) [contains metacresol, phenol]
SUBQ: For SUBQ administration into the thigh, upper arm, or abdomen; do not administer IM or IV, or in an insulin infusion pump. Absorption rates vary amongst injection sites; be consistent with area used while rotating 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. Insulin icodec should be administered once weekly on the same day each week at any time of the day.
The FlexTouch pen delivers doses in 10-unit increments and can deliver up to 700 units in a single injection. If the required dose is >700 units, the dose should be split into 2 injections. The dose window for FlexTouch pens shows the number of insulin units to be delivered. Do not dilute or mix insulin icodec with any other insulin formulation or solution; do not transfer from the FlexTouch pen into a syringe for administration. Prime the needle before each injection with 10 units of insulin (use a new needle for each injection). Once injected, continue to depress the button until the dial has returned to 0 and for an additional 6 seconds. Then, remove the needle.
Diabetes mellitus, types 1 and 2, treatment: To improve glycemic control in adults with type 1 or type 2 diabetes mellitus.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (insulins, all formulations and strengths, SUBQ, IV) 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.
Insulin icodec is not intended for IV or IM administration.
Cross contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the 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
Effective contraception is recommended for patients who could become pregnant, including those immediately postpartum. Pregnancy should be planned when optimal glycemic control is achieved (ADA 2024).
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 (ACOG 2018; ADA 2024).
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 2018; ADA 2024).
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. Use of a preparation with pregnancy data from randomized controlled trials is preferred (ADA 2024). Use of insulin icodec during pregnancy is not recommended by the manufacturer.
It is not known if insulin icodec is present in breast milk.
Breastfeeding is not recommended by the manufacturer.
Diabetes mellitus: Blood glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2024); 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 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 2024; 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]).
HbA 1c: 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 2024; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (AACE [Samson 2023]; ADA 2024):
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 2024):
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 2024):
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 2024).
Gestational diabetes mellitus (ACOG 2018; ADA 2024):
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 2024):
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 2024): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L).
Recommendations for hospitalized adult patients with hyperglycemia:
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 2024).
Classification of hypoglycemia (ADA 2024):
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.
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. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. 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 Escherichia coli or Saccharomyces cerevisiae. Insulin icodec differs from human insulin by the omission of the amino acid threonine in position B30, substitution of the tyrosine in position A14 with glutamine, and substitution of both the tyrosine in position B16 and the phenylalanine in position B25 with histidine. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin icodec is an ultra-long-acting, human insulin analog that binds reversibly to albumin, creating a depot from which insulin icodec is slowly released.
Onset: Peak effect: 2 to 4 days.
Duration: ≥168 hours (Pieber 2023).
Distribution: Vd: 9.79 L.
Protein binding: >99% (albumin).
Half-life elimination: ~1 week (independent of dose).
Time to peak: 15 to 18 hours.
