Insulin: A Comprehensive Overview

Insulin is a vital polypeptide hormone that plays a central role in glucose homeostasis, particularly in individuals with diabetes mellitus. Synthesised by beta cells in the pancreatic islets of Langerhans, insulin facilitates glucose uptake into muscle and adipose tissues while suppressing hepatic glucose production. In type 1 diabetes, endogenous insulin secretion is absent, whereas in type 2 diabetes, insulin resistance or impaired secretion necessitates exogenous administration. Clinically formulated insulin is essential for controlling hyperglycaemia and preventing both microvascular and macrovascular diabetic complications.

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Types and Uses

Insulin preparations vary based on their onset, peak, and duration of action. They are classified as follows:

Rapid-Acting Insulin (e.g., insulin lispro, aspart, glulisine): Begins action within 10–30 minutes, peaks at 30–90 minutes, and is suitable for managing postprandial glucose surges.
Short-Acting Insulin (e.g., regular insulin): Onset within 30–60 minutes, with a 2–4 hour peak. Administered before meals or intravenously in acute cases such as diabetic ketoacidosis (DKA).
Intermediate-Acting Insulin (e.g., NPH): Starts working in 1–2 hours, lasting 12–18 hours. Often combined with short-acting insulin for basal coverage.
Long-Acting Insulin (e.g., glargine, detemir): Provides steady basal insulin levels for 24 hours or more with minimal peak.
Ultra-Long-Acting Insulin (e.g., degludec): Offers over 42 hours of glycaemic control, improving adherence and reducing hypoglycaemic episodes.
Premixed Insulins: Fixed combinations of basal and prandial insulin (e.g., 70/30, 75/25) that simplify therapy, particularly in type 2 diabetes.

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Dosage and Administration

Insulin therapy must be tailored to individual needs. In type 1 diabetes, initial doses typically range from 0.4–1.0 units/kg/day, divided into basal and bolus components. In type 2 diabetes, therapy often begins at 0.1–0.2 units/kg/day, especially when combined with oral agents.

Routes of administration include:

Subcutaneous injections (via syringe or pen)
Continuous Subcutaneous Insulin Infusion (CSII) using insulin pumps
Intravenous infusion, primarily for regular insulin in hospitalised patients
Inhaled insulin (e.g., Technosphere insulin) for rapid prandial coverage

Dose Adjustments in Special Conditions

Renal Impairment: Impaired renal clearance heightens insulin's duration, necessitating dose reductions and vigilant glucose monitoring.
Hepatic Impairment: Altered insulin metabolism in hepatic dysfunction requires careful titration and increased frequency of blood glucose assessments.
Pregnancy: Physiological insulin resistance increases during the second and third trimesters. Dose adjustments are crucial for maternal and foetal wellbeing, with basal-bolus regimens and close monitoring as standard practice.

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Effects and Side Effects

Insulin promotes cellular glucose uptake, glycogenesis, lipogenesis, and protein synthesis while inhibiting gluconeogenesis. This action is central to preventing chronic complications of diabetes.

Common adverse effects include:

Hypoglycaemia
Weight gain
Lipodystrophy (either lipohypertrophy or lipoatrophy)
Localised injection site reactions

Rare but serious reactions:

Generalised insulin allergy
Insulin oedema
Formation of anti-insulin antibodies

Drug Combinations and Infusion Considerations

Insulin is frequently combined with:

Metformin: Lowers hepatic glucose output and enhances insulin sensitivity.
GLP-1 receptor agonists: Reduce appetite, slow gastric emptying, and support weight loss.
SGLT2 inhibitors: Promote urinary glucose excretion.
DPP-4 inhibitors: Prolong incretin activity.

During insulin infusion therapy:

Monitor blood glucose hourly
Regularly assess serum potassium levels (risk of hypokalaemia)
Use appropriate IV fluids (typically normal saline)
Maintain a dedicated infusion line and verify pump settings

Presentation and Dosage Table

Type	Example	Onset	Peak	Duration	Dosage Guidance
Rapid-Acting	Lispro, Aspart	10–30 mins	30–90 mins	3–5 hours	0.5–1 units/kg/day, in divided doses
Short-Acting	Regular Insulin	30–60 mins	2–4 hours	5–8 hours	0.1 units/kg pre-meal
Intermediate-Acting	NPH	1–2 hours	4–12 hours	12–18 hours	Once or twice daily
Long-Acting	Glargine, Detemir	1–2 hours	Minimal	24 hours	Once daily, same time each day
Ultra-Long-Acting	Degludec	~1 hour	Minimal	>42 hours	Once daily, flexible timing
Premixed	70/30, 75/25	15–60 mins	Dual peaks	Up to 24 hrs	1–2 times/day before meals

Pharmacokinetics, Pharmacodynamics, and Pathogen Coverage

Insulin’s absorption rate is influenced by injection site, depth, and formulation. Rapid-acting insulins are absorbed quickly, ideal for mealtime administration. Long-acting insulins maintain stable basal levels without prominent peaks.

Pharmacodynamically, insulin activates GLUT4 transporters in muscle and adipose tissue, suppresses hepatic glucose production, and promotes anabolic metabolism. While insulin has no direct antimicrobial activity, optimal glycaemic control indirectly enhances immune function and mitigates infection risk.

Drug Interactions

Beta-blockers: Can mask hypoglycaemia symptoms
Corticosteroids and thiazides: Increase blood glucose levels and insulin requirements
Alcohol: Increases the risk of hypoglycaemia
MAO inhibitors and salicylates: Potentiate insulin action

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Comparison with Other Agents

Drug Class	Drug Name	Duration	Route	Unique Benefit
Long-acting Insulin	Glargine	24 hours	Subcutaneous	Flat basal profile
Intermediate Insulin	NPH	12–18 hours	Subcutaneous	Economical
Premixed Insulin	70/30	Up to 24 hrs	Subcutaneous	Convenient for fixed schedules
Oral Antidiabetic	Metformin	8–12 hours	Oral	Cardioprotective, weight neutral
GLP-1 Agonist	Semaglutide	1 week	Subcutaneous	Significant weight loss, CV benefit

Precautions and Special Considerations

Store insulin between 2–8°C and avoid freezing
Inspect vials for cloudiness or particulate matter before use
Rotate injection sites to prevent lipodystrophy
Educate patients on recognising and treating hypoglycaemia
Adjust regimens in elderly or those with cognitive impairment

Toxicity and Overdose

Excess insulin administration causes hypoglycaemia, with symptoms such as confusion, dizziness, seizures, or coma.

Management includes:

Mild cases: Oral glucose intake
Moderate to severe cases: IV 50% dextrose or IM glucagon
Refractory hypoglycaemia: ICU admission and continuous glucose infusion

Recent Updates and 2025 Guidelines

Significant 2025 updates include:

Wider adoption of AI-integrated closed-loop insulin delivery systems
CGM-guided insulin titration becoming standard in type 1 diabetes
Expanded use of biosimilar insulins to improve accessibility
Availability of ultra-rapid insulin analogues for improved mealtime control
Updated NICE and ADA guidelines advocating individualised glycaemic targets and integrating patient preference into treatment decisions

Key Facts to Remember

Insulin is indispensable for type 1 diabetes management
Do not shake insulin vigorously; roll NPH gently to mix
Always label insulin vials with date of opening
Differentiate between basal and bolus preparations
Continuous glucose monitors enhance treatment precision and safety

References

American Diabetes Association. (2025). Standards of Medical Care in Diabetes.
National Institute for Health and Care Excellence (NICE). (2024). Type 1 Diabetes in Adults: Diagnosis and Management.
World Health Organization. (2024). WHO Model List of Essential Medicines.
Mayo Clinic. (2024). Insulin Therapy: Clinical Insights.
British National Formulary (BNF). (2025). Insulin Preparations and Clinical Use.