Insulin

INN: Insulin
Drug Class: Hormone – Blood glucose regulator
Pharmacological Class: Peptide hormone; antihyperglycemic agent
Therapeutic Class: Antidiabetic agent
Regulatory Status: Prescription-only
ATC Code: A10A (Insulins and analogues)
Sources of Insulin: Human recombinant DNA technology (biosynthetic); some older animal-sourced (bovine or porcine) insulins exist but are largely obsolete

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Overview

Insulin is a peptide hormone produced by the β-cells of the pancreatic islets of Langerhans. It plays a central role in the regulation of glucose homeostasis by facilitating the uptake of glucose into cells, promoting glycogenesis, and inhibiting gluconeogenesis and lipolysis. In patients with diabetes mellitus—especially type 1 diabetes, but also sometimes type 2—insulin therapy is necessary to replace or supplement endogenous insulin secretion.

Synthetic or biosynthetic insulin preparations are used to manage blood glucose levels. These include regular human insulin and analogs with modified pharmacokinetics designed to act more rapidly, more slowly, or over longer durations.

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Mechanism of Action

Insulin exerts its effects by binding to insulin receptors on cell surfaces, primarily in muscle, fat, and liver cells. Binding activates the insulin receptor tyrosine kinase, which initiates a cascade of phosphorylation events and signaling pathways:

• Increases glucose transporter (GLUT4) translocation to cell membranes, enhancing glucose uptake

• Stimulates glycogen synthesis via activation of glycogen synthase

• Inhibits hepatic glucose production

• Suppresses lipolysis and proteolysis

• Promotes lipid synthesis

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Types of Insulin

Insulin products are categorized based on their onset, peak, and duration of action:

1. Rapid-Acting Insulins

• Examples: Insulin lispro (Humalog), insulin aspart (NovoLog), insulin glulisine (Apidra)

• Onset: 10–30 minutes

• Peak: 30 minutes–3 hours

• Duration: 3–5 hours

• Use: Administered before meals to control postprandial hyperglycemia

2. Short-Acting Insulins

• Example: Regular insulin (Humulin R, Novolin R)

• Onset: 30–60 minutes

• Peak: 2–4 hours

• Duration: 6–10 hours

• Use: Pre-meal injection; also used intravenously in emergencies (e.g., diabetic ketoacidosis)

3. Intermediate-Acting Insulins

• Example: NPH insulin (Humulin N, Novolin N)

• Onset: 1–3 hours

• Peak: 4–12 hours

• Duration: 12–18 hours

• Use: Often combined with rapid or short-acting insulins

4. Long-Acting Insulins

• Examples: Insulin glargine (Lantus, Toujeo), insulin detemir (Levemir), insulin degludec (Tresiba)

• Onset: 1–4 hours

• Peak: Minimal or no peak

• Duration: Up to 24–42 hours

• Use: Basal insulin to maintain fasting glucose

5. Pre-Mixed Insulins

• Examples: 70/30 (NPH/regular), 75/25 (lispro protamine/lispro), 70/30 (aspart protamine/aspart)

• Use: Covers both basal and prandial insulin needs in fewer injections

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Indications

1. Type 1 Diabetes Mellitus

   • Essential, lifelong therapy due to absolute insulin deficiency

2. Type 2 Diabetes Mellitus

   • When oral antidiabetic agents fail or are contraindicated

   • During periods of stress, illness, or pregnancy

3. Gestational Diabetes

   • When dietary modifications are insufficient to achieve glycemic targets

4. Hyperkalemia (adjunct)

   • Drives potassium into cells when combined with glucose

5. Diabetic Ketoacidosis (DKA)

   • Regular insulin given IV in a hospital setting to reverse ketogenesis

6. Hyperosmolar Hyperglycemic State (HHS)

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Dosage and Administration

• Individualized based on patient’s weight, age, insulin sensitivity, and blood glucose targets

• Type 1 diabetes: Basal-bolus regimen common (e.g., glargine + rapid-acting insulin with meals)

• Type 2 diabetes: May start with basal insulin alone; dose titrated according to fasting blood glucose

• Total daily insulin requirement (TDD): 0.4–1.0 units/kg/day (varies by patient)

Routes of Administration:

• Subcutaneous (routine use)

• Intravenous (short-acting insulin for emergencies)

• Inhaled (e.g., Afrezza – limited use)

• Intramuscular (rarely used)

Devices:

• Vials and syringes

• Insulin pens

• Insulin pumps (CSII – continuous subcutaneous insulin infusion)

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Contraindications

• Hypoglycemia

• Known hypersensitivity to insulin or its excipients (may vary by product)

• Relative caution in patients with hypokalemia or liver dysfunction

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Precautions and Monitoring

• Blood glucose monitoring: Frequent checks required for dose adjustment and hypoglycemia prevention

• HbA1c: Targeted every 3–6 months to assess long-term control

• Renal/hepatic dysfunction: May require dose adjustment due to altered metabolism and clearance

• Injection site rotation: Prevent lipodystrophy

• Dose timing: Must be synchronized with meals (especially short- and rapid-acting insulins)

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Adverse Effects

Common

• Hypoglycemia: Most serious and frequent adverse effect; can be life-threatening

• Weight gain: Due to anabolic effect

• Injection site reactions: Redness, swelling, or pruritus

Less Common

• Lipohypertrophy or lipoatrophy: Fat tissue abnormalities at injection sites

• Allergic reactions: Rare with human insulin

• Hypokalemia: Especially when used intravenously

• Edema: May occur due to sodium retention in early therapy

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Drug Interactions

Potentiation of Hypoglycemia:

• Oral antidiabetic agents (e.g., sulfonylureas, metformin)

• Beta-blockers (mask symptoms of hypoglycemia)

• Alcohol

• Salicylates

• ACE inhibitors

• MAO inhibitors

Antagonism of Insulin Effect (Hyperglycemia Risk):

• Corticosteroids

• Thiazide diuretics

• Sympathomimetics (e.g., epinephrine)

• Atypical antipsychotics (e.g., olanzapine)

• Niacin

• Danazol

Other Interactions:

• Beta-blockers: May blunt sympathetic signs of hypoglycemia (e.g., tachycardia)

• GLP-1 analogs or SGLT2 inhibitors: Often co-administered in Type 2 diabetes; require careful adjustment

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Pharmacokinetics (Varies by Formulation)

• Absorption: SC route bioavailability ~70–80%; varies by site (abdomen > arm > thigh)

• Distribution: Does not cross BBB; binds weakly to plasma proteins

• Metabolism: Degraded in liver, kidneys, and target tissues

• Half-life: Short (minutes); duration determined by formulation additives (e.g., protamine, zinc)

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Insulin Resistance

• Occurs in obesity, metabolic syndrome, infection, inflammation

• Requires higher doses for glucose control

• Associated with receptor/post-receptor defects

• Often managed with lifestyle modification, metformin, or insulin sensitizers

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Special Populations

• Pregnancy: Human insulin is the gold standard; does not cross the placenta

• Elderly: Risk of hypoglycemia increased; simplified regimens preferred

• Children: Insulin is mandatory in pediatric Type 1 diabetes; dose based on weight and growth stage

• Renal impairment: Clearance reduced; requires lower doses and increased monitoring

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Storage and Stability

• Unopened vials or pens: Refrigerate (2–8°C)

• Opened vials/pens: Can be stored at room temperature (~25°C) for 28 days (varies by brand)

• Do not freeze insulin

• Protect from direct sunlight and excessive heat

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Patient Education and Counseling Points

• Recognize signs of hypoglycemia: shakiness, sweating, confusion, irritability

• Always carry glucose or glucagon

• Inject into clean, dry skin; rotate sites

• Monitor blood glucose regularly

• Ensure understanding of timing with meals

• Keep extra insulin on hand; monitor expiration dates

• Travel tips: Carry insulin in hand luggage; notify security

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Advances and Future Therapies

• Ultra-long-acting insulins: Insulin icodec (weekly dosing under investigation)

• Closed-loop insulin delivery: “Artificial pancreas” with continuous glucose monitoring and automated insulin pump systems

• Oral insulin and transdermal patches: Under development for non-invasive delivery

• Biosimilar insulins: Affordable alternatives to branded analogs (e.g., Semglee vs. Lantus)

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Examples of Branded Insulin Products

Type	Brand	Generic
Rapid-Acting	Humalog	Insulin lispro
Rapid-Acting	NovoLog	Insulin aspart
Short-Acting	Humulin R	Regular insulin
Intermediate	Humulin N	NPH insulin
Long-Acting	Lantus	Insulin glargine
Long-Acting	Levemir	Insulin detemir
Long-Acting	Tresiba	Insulin degludec
Inhaled	Afrezza	Inhaled human insulin