Introduction
Humalog (insulin lispro) is a rapid-acting human insulin analog used for the management of diabetes mellitus. Developed as a recombinant DNA-derived human insulin analog, it was designed to provide more physiologic insulin replacement by mimicking the body's natural prandial insulin response. Humalog offers faster onset and shorter duration of action compared to regular human insulin, making it particularly valuable for mealtime glucose control.
Mechanism of Action
Humalog exerts its effects through the same mechanism as endogenous insulin. It binds to insulin receptors on target cells (primarily muscle, fat, and liver tissues), initiating a cascade of intracellular signaling events. This binding promotes cellular glucose uptake, inhibits hepatic glucose production, promotes protein synthesis, and inhibits lipolysis. The structural modification of insulin lispro (reversal of proline and lysine at positions B28 and B29) reduces self-association into hexamers, allowing for more rapid dissociation into monomers after subcutaneous injection and consequently faster absorption into the bloodstream.
Indications
- Treatment of type 1 diabetes mellitus
- Treatment of type 2 diabetes mellitus
- Continuous subcutaneous insulin infusion (insulin pump therapy)
- Use in combination with longer-acting insulins for basal-bolus regimens
Dosage and Administration
Standard dosing: Highly individualized based on metabolic needs, blood glucose monitoring results, and glycemic control goals Administration:- Subcutaneous injection (abdomen, thigh, buttocks, or upper arm)
- Typically administered 0-15 minutes before meals
- May be administered intravenously under medical supervision
- Renal impairment: Reduced insulin requirements may be necessary
- Hepatic impairment: Reduced insulin requirements may be necessary
- Elderly: Monitor closely for hypoglycemia
- Pregnancy: Category B - requires careful glucose monitoring and dose adjustment
Pharmacokinetics
Absorption: Rapid subcutaneous absorption with onset of action within 15 minutes Peak effect: 30-90 minutes after administration Duration: 3-5 hours Distribution: Circulates in blood bound to plasma proteins Metabolism: Primarily metabolized in liver, kidney, and muscle tissues Elimination: Renal elimination of metabolites; half-life approximately 1 hourContraindications
- Hypersensitivity to insulin lispro or any component of the formulation
- During episodes of hypoglycemia
- In insulin infusion pumps that are not approved for use with Humalog
Warnings and Precautions
- Hypoglycemia: Most common adverse effect; can be severe and life-threatening
- Hypokalemia: May cause potassium shifts leading to hypokalemia
- Lipodystrophy: May occur at injection sites
- Weight gain: Can occur with insulin therapy
- Peripheral edema: Particularly with improved glycemic control
- Allergic reactions: Both local and systemic reactions possible
- Medication errors: Potential for confusion with other insulin products
Drug Interactions
Drugs that may increase hypoglycemic risk:- Oral antidiabetic agents
- ACE inhibitors
- Disopyramide
- Fluoxetine
- MAO inhibitors
- Pentoxifylline
- Propoxyphene
- Salicylates
- Somatostatin analogs
- Sulfonamide antibiotics
- Corticosteroids
- Danazol
- Diuretics
- Estrogens
- Glucagon
- Isoniazid
- Niacin
- Phenothiazines
- Protease inhibitors
- Somatropin
- Sympathomimetic agents
- Thyroid hormones
Adverse Effects
Common (>10%):- Hypoglycemia
- Injection site reactions (redness, swelling, itching)
- Weight gain
- Hypokalemia
- Peripheral edema
- Lipodystrophy
- Allergic reactions
- Anaphylaxis
- Severe hypoglycemia requiring assistance
Monitoring Parameters
- Blood glucose levels (fasting and postprandial)
- HbA1c every 3 months until stable, then every 6 months
- Hypoglycemia symptoms and awareness
- Injection site rotation and examination
- Weight changes
- Renal and hepatic function in patients with impairment
- Potassium levels in at-risk patients
Patient Education
- Proper injection technique and site rotation
- Recognition and treatment of hypoglycemia symptoms
- Importance of consistent meal timing with insulin administration
- Never share pens or needles
- Proper storage (refrigerate unopened vials/pens; room temperature for in-use products)
- Carry glucose source at all times
- Wear diabetes identification
- Regular blood glucose monitoring
- When to seek medical attention (severe hypoglycemia, illness, surgery)
- Travel considerations (time zone changes, storage)
References
1. American Diabetes Association. Standards of Medical Care in Diabetes - 2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 2. Plank J, et al. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care. 2005;28(5):1107-1112. 3. Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):174-183. 4. Humalog [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022. 5. Seaquist ER, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013;36(5):1384-1395. 6. Inzucchi SE, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2022;45(11):2753-2786.