Injectable therapy is essential in type 1 diabetes and frequently required in type 2 diabetes, gestational diabetes, pancreatic diabetes, severe hyperglycaemia, diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS), surgery and acute illness. This lesson integrates insulin pharmacology, preparation selection, practical dosing, injection technique, regimen design, GLP-1 receptor agonists and emergency use. Every dose must be individualised to the patient, product concentration, meal pattern, renal function, glucose readings and local protocol.
Learning objectives
- Explain insulin structure, receptor action and why it must usually be injected.
- Compare rapid-, short-, intermediate-, long-acting and premixed insulins by timing and clinical role.
- Calculate safe starting doses, basal–bolus regimens, correction doses and emergency IV insulin concepts without confusing units or concentrations.
- Teach vial, syringe, pen, pump and injection-site safety, including U-40/U-100 errors and lipodystrophy prevention.
- Use GLP-1 receptor agonists safely, including titration, contraindications and recognition of pancreatitis or dehydration.
- Manage hypoglycaemia, DKA, HHS and peri-operative insulin problems as emergencies.
1. When injectable therapy is indicated
| Situation | Why injectable treatment is needed |
|---|---|
| Type 1 diabetes | Absolute beta-cell failure; insulin is required lifelong to prevent ketosis and death. |
| Type 2 diabetes with severe symptomatic hyperglycaemia | Polyuria, polydipsia, weight loss, ketosis or very high glucose may indicate insulin deficiency requiring rapid control. |
| Oral-agent failure or intolerance | Progressive beta-cell dysfunction may make basal or basal–bolus insulin necessary. |
| DKA or HHS | IV fluids, IV insulin and electrolyte management are emergency treatments. |
| Major surgery, sepsis or acute myocardial/cerebral illness | Stress hormones raise glucose and oral drugs may be unsafe during fasting, renal injury or haemodynamic instability. |
| Gestational diabetes not controlled with nutrition therapy | Insulin is commonly preferred when medication is needed; follow obstetric protocol. |
| Pancreatic diabetes, steroid-induced diabetes or endocrine disease | Insulin requirements vary with endogenous insulin reserve and steroid exposure. |
2. Insulin: structure and mechanism
Human insulin is a 51-amino-acid polypeptide composed of A and B chains linked by disulfide bonds. Beta cells release insulin and C-peptide from proinsulin in response to glucose. Recombinant human insulin is produced using engineered bacteria or yeast. Peptide insulin is destroyed by gastrointestinal proteases, so routine therapy is parenteral.
- Insulin binds the transmembrane insulin receptor, a receptor tyrosine kinase.
- Autophosphorylation activates IRS–PI3K–Akt and other pathways.
- GLUT4 transporters move to the skeletal-muscle and adipocyte membrane, increasing glucose uptake.
- Insulin promotes glycogen, fat and protein synthesis; suppresses hepatic gluconeogenesis, glycogenolysis, lipolysis and ketogenesis; and shifts potassium into cells.
Insulin lowers glucose and potassium. In DKA, potassium may initially appear normal or high despite total-body depletion; never begin insulin without checking potassium and replacing it when required by protocol.
3. Insulin preparations and time-action profiles
| Class/examples | Approximate onset/peak/duration | Timing and main role |
|---|---|---|
| Rapid acting: lispro, aspart, glulisine | Onset about 5–15 min; peak about 1–2 h; duration 3–5 h | Inject immediately before eating (product-specific; aspart is commonly within 5–10 min before a meal) or lispro within 15 min before/immediately after. Meal bolus and correction. |
| Short acting: regular human insulin | Onset 30–60 min; peak 2–4 h; duration 5–8 h (variable) | Usually inject 30 minutes before a meal. The only commonly used insulin that can be given IV in emergencies, using a protocol-approved formulation. |
| Intermediate: NPH/isophane | Onset 1–2 h; peak 4–12 h; duration 12–18 h (variable) | Once or twice daily basal coverage; cloudy suspension that must be gently resuspended. |
| Long acting: glargine U-100/U-300, detemir | Relatively flat; about 20–36 h depending on product | Basal insulin once daily (detemir may require twice daily); do not mix glargine or detemir in the same syringe. |
| Ultra-long: degludec | Flat profile; duration beyond 42 h in many adults | Once daily basal; flexible timing in adults only as the label permits, while maintaining at least the required interval. |
| Premixed human 30/70 | Regular plus NPH | Inject about 30 minutes before meals, usually twice daily. |
| Premixed analogue 25/75 or 30/70 | Rapid analogue plus protaminated analogue | Inject shortly before meals; typically twice daily, with product-specific timing. |
| Co-formulation 30% aspart/70% degludec (for example, Ryzodeg) | Meal-time rapid component plus basal component | Individualise meal dosing; do not substitute units between products without a conversion plan. |
Onset, peak and duration vary with injection site, dose, temperature, exercise, renal function and product. Treat these times as teaching ranges, not permission to interchange brands.
4. Practical insulin dosing
4.1 Starting basal insulin in insulin-naïve type 2 diabetes
- Common starting options: 10 units once daily or approximately 0.1–0.2 units/kg/day of glargine, degludec, detemir or NPH.
- Titrate by 2 units every 3 days, or 10–15% once or twice weekly, toward the fasting glucose target while avoiding nocturnal hypoglycaemia. The local protocol determines the target.
- If fasting glucose is low or nocturnal hypoglycaemia occurs, reduce basal insulin by about 10–20% and investigate meals, alcohol, renal function and timing.
4.2 Type 1 total daily dose and basal–bolus
Newly diagnosed adults often start around 0.2–0.4 units/kg/day when residual insulin secretion or hypoglycaemia risk is significant; established type 1 diabetes frequently requires approximately 0.4–1.0 units/kg/day, adjusted individually. Give about 40–50% as basal and the remainder as pre-meal boluses. Start lower in renal failure, frailty, pregnancy or recurrent hypoglycaemia.
- Carbohydrate ratio: the 500 rule is a teaching estimate: 500 divided by total daily dose gives grams of carbohydrate covered by 1 unit of rapid insulin.
- Correction factor: the 1800 rule estimates the fall in mg/dL from 1 unit of rapid insulin; use 100 instead of 1800 when working in mmol/L-based local protocols after appropriate conversion. Never use a correction factor without a clinician-approved plan.
- Basal testing: fasting and overnight trends—not a single glucose—guide basal adjustment. Frequent nocturnal lows mean the basal dose is too high or meals/exercise need review.
4.3 Prandial and correction insulin
Rapid insulin is calculated from carbohydrate intake plus a correction for pre-meal hyperglycaemia. If the patient is not eating, scheduled meal insulin is usually withheld but basal insulin is not stopped in type 1 diabetes. Hospitals often use a validated basal–bolus or variable-rate IV insulin protocol rather than an improvised sliding scale.
4.4 Premixed regimens
- Premixed insulin is useful when meals and schedules are regular and a simpler regimen is needed.
- A common approach is twice-daily dosing: approximately two-thirds before breakfast and one-third before the evening meal, then titrate according to pre-meal and fasting readings. Exact starting units must be individualised.
- Premixed insulin is less flexible than basal–bolus and is hazardous when meals are skipped. Do not mix different premixes or alter the ratio without a prescription.
5. Injectable insulin administration
5.1 Syringe from a vial
- Wash hands, check the insulin name, concentration, expiry, appearance and storage.
- Use the syringe that matches the concentration. U-40 insulin requires a U-40 syringe; U-100 insulin requires a U-100 syringe. Never convert by guessing.
- Inject air equal to the prescribed dose into the vial, invert, withdraw insulin, remove bubbles and recheck the units.
- Choose abdomen, thigh, upper arm or buttock; rotate within a region to reduce lipodystrophy.
- Insert into subcutaneous tissue, inject steadily, hold the needle in place for about 5–10 seconds as the device instructions direct, then withdraw safely.
5.2 Pens and pumps
- Use a new pen needle for each injection, prime as instructed, dial the correct units and never share a pen, even with a new needle.
- Insulin pumps deliver rapid-acting insulin continuously through a subcutaneous cannula. Interruption can cause DKA within hours; patients need a backup injection plan and ketone testing.
- Change cannula/sites according to the pump manufacturer, inspect for redness or leakage and confirm the pump is delivering before correcting high glucose.
5.3 Concentration safety
| Concentration | Meaning | Safety rule |
|---|---|---|
| U-40 | 40 units/mL | Use U-40 syringe or an approved device; a U-100 syringe can deliver a dangerous overdose if markings are misread. |
| U-100 | 100 units/mL | Use U-100 syringe/pen; do not draw U-200/U-300/U-500 insulin into a standard syringe. |
| U-200, U-300, U-500 | Concentrated products | Use only the dedicated pen/device and express the dose in units, never mL alone. Verify with a second clinician in hospital. |
5.4 Mixing insulin
Regular insulin may be mixed with NPH in the same syringe when prescribed: draw clear (regular) before cloudy (NPH). Never mix glargine, detemir, degludec or most premixed preparations with another insulin. Follow the product label and local policy.
6. Insulin adverse effects and precautions
| Effect | Mechanism/feature | Prevention and response |
|---|---|---|
| Hypoglycaemia | Excess insulin relative to food, exercise or renal clearance | Confirm glucose, treat rapidly, investigate timing and reduce the relevant dose. |
| Weight gain | Reduced glycosuria and anabolic effect | Nutrition/exercise review; avoid intentional underdosing. |
| Lipohypertrophy | Repeated injections at one site | Rotate sites; do not inject into a lump because absorption is unpredictable. |
| Lipoatrophy | Rare immune/local reaction | Change site and assess for allergy. |
| Local allergy or systemic hypersensitivity | Reaction to insulin or excipient | Urgent assessment for urticaria, wheeze or hypotension; do not simply stop essential insulin without an alternative. |
| Hypokalaemia | Insulin drives potassium intracellularly | Monitor potassium in DKA/HHS and replace according to protocol. |
| Oedema | Renal sodium retention after glycaemic improvement | Assess cardiac/renal causes and review dose escalation. |
7. GLP-1 receptor agonists
GLP-1 receptor agonists are injectable incretin mimetics used mainly in type 2 diabetes and, for selected products, obesity or cardiovascular-risk reduction. They increase glucose-dependent insulin, reduce glucagon, slow gastric emptying and increase satiety. They are not insulin and must not be used as sole therapy for type 1 diabetes or DKA.
| Agent | Typical adult diabetes regimen | Half-life/interval |
|---|---|---|
| Exenatide twice daily | 5 micrograms SC twice daily within 60 minutes before morning and evening meals; after at least one month may increase to 10 micrograms twice daily. | About 2.4 h; twice daily. |
| Exenatide extended release | 2 mg SC once weekly on the same day each week. | About 14 days; weekly. |
| Lixisenatide | 10 micrograms once daily for 14 days, then 20 micrograms once daily, usually within one hour before the first meal. | About 3 h; once daily. |
| Liraglutide | 0.6 mg SC once daily for one week (starter dose), then 1.2 mg daily; may increase to 1.8 mg daily for glycaemic control. | About 13 h; once daily. |
| Dulaglutide | 0.75 mg SC once weekly initially; increase to 1.5 mg and, where approved, higher weekly doses after at least four weeks at each step. | About 4 days; weekly. |
| Semaglutide injection | 0.25 mg SC once weekly for four weeks (starter, not therapeutic), then 0.5 mg weekly; increase to 1 mg or 2 mg weekly only as product and response permit. | About one week; weekly. |
Benefits
- Glucose lowering with low hypoglycaemia risk unless combined with insulin or a secretagogue.
- Weight loss and reduced appetite; some agents have proven cardiovascular benefit in appropriate populations.
- Some agents may reduce albuminuria or cardiovascular risk, but they are not substitutes for blood-pressure, lipid and renal care.
Adverse effects and contraindications
- Nausea, early satiety, vomiting, diarrhoea or constipation—titrate slowly and maintain hydration.
- Acute pancreatitis is rare but serious: stop the drug and investigate persistent severe abdominal pain radiating to the back with vomiting.
- Gallbladder disease, dehydration-related acute kidney injury, delayed gastric emptying and worsening of diabetic retinopathy during rapid glucose improvement can occur.
- Avoid or seek specialist advice in severe gastroparesis, active pancreatitis, pregnancy or significant dehydration.
- Contraindicated for products carrying the warning in patients with personal/family history of medullary thyroid carcinoma or MEN2.
- Do not combine two GLP-1 receptor agonists or a GLP-1 receptor agonist with a DPP-4 inhibitor.
8. Insulin regimens
| Regimen | Structure | When useful | Limitations |
|---|---|---|---|
| Basal only | One long/intermediate-acting injection daily | Type 2 diabetes with fasting hyperglycaemia or as first injectable step | Does not control meal spikes; over-titration causes nocturnal hypoglycaemia. |
| Oral agent + basal | Continue selected oral medicines plus basal insulin | Common type 2 strategy; metformin often continued if safe | Secretagogues may need reduction or discontinuation. |
| Basal-plus | Basal insulin plus one rapid meal bolus, then additional meals if needed | Postprandial hyperglycaemia with fewer injections than full basal–bolus | Requires meal and glucose education. |
| Basal–bolus | Long/ultra-long basal plus rapid insulin before each meal | Type 1 diabetes, pregnancy or marked meal-related excursions | Most flexible but highest education and hypoglycaemia burden. |
| Premixed OD/BID | Fixed rapid/short plus intermediate component | Regular meal schedule or resource-limited settings | Less flexible; missed meals cause hypoglycaemia. |
| CSII/pump | Continuous rapid insulin with meal boluses | Selected type 1 patients with education and reliable supplies | Interruption quickly causes ketosis; requires backup plan. |
9. Emergency insulin therapy
9.1 DKA
- Assess airway, breathing, circulation, mental status and precipitating cause; obtain venous blood gas, electrolytes, glucose, ketones, renal function, ECG and infection/ischemia tests.
- Start isotonic crystalloid according to haemodynamic status and local protocol.
- Check potassium before insulin. If potassium is severely low, replace potassium and delay insulin until safe. If potassium is normal/low-normal, add replacement while insulin runs as protocol directs.
- Use IV regular insulin, commonly 0.1 units/kg/hour after local protocol decisions. A bolus is not universal and should not be improvised.
- When glucose falls but ketonaemia persists, add dextrose while continuing insulin to close the anion gap and clear ketones.
- Search for infection, missed insulin, myocardial infarction, stroke, pancreatitis, drugs or pump failure. Transition to SC basal insulin with overlap before stopping IV insulin.
9.2 HHS
Fluids are the immediate priority. Correct sodium and osmolality gradually, monitor potassium and start IV insulin after adequate fluid resuscitation according to protocol. Avoid rapid osmotic shifts and monitor neurological status. Treat the trigger.
9.3 Intravenous insulin safety
Use a dedicated infusion pump, concentration-labelled line, hourly glucose checks initially, frequent potassium/electrolyte checks and a written hospital protocol. Never use a patient’s home concentrated pen to improvise an IV infusion.
10. Treating insulin-induced hypoglycaemia
- Conscious and able to swallow: give 15–20 g fast-acting carbohydrate (glucose gel/tablets or sugary drink), recheck in 15 minutes and repeat until corrected; then provide a longer-acting carbohydrate or meal.
- Unconscious, seizing or unable to swallow: recovery position, airway protection, IV dextrose or IM glucagon per local protocol; check for trauma and recurrent hypoglycaemia.
- Long-acting insulin or pump overdose: prolonged observation, serial glucose/electrolytes and specialist consultation may be required.
- Driving/work: counsel patients to check glucose before driving and carry rapid glucose; recurrent unawareness requires specialist review.
11. Storage, transport and patient education
- Store unopened insulin refrigerated as the product label directs; do not freeze or use insulin exposed to excessive heat or direct sunlight.
- In-use pens/vials have product-specific room-temperature expiry. Write the opening date and discard after the labelled interval.
- Cloudy NPH/premix should be gently rolled to resuspend; clear rapid and long-acting solutions should not be used if cloudy, discoloured or particulate unless the label specifically allows suspension.
- Carry identification and a carbohydrate source; teach family members how to administer glucagon where available.
- Never share needles, syringes or pens. Dispose of sharps in a puncture-resistant container.
- During vomiting, fever or infection, never stop basal insulin in type 1 diabetes without urgent clinical advice. Check glucose and ketones and follow sick-day rules.
12. Important interactions
| Interaction | Effect | Action |
|---|---|---|
| Beta-blockers | May mask tremor, palpitations and other adrenergic warnings of hypoglycaemia. | Teach patients to recognise sweating, confusion and neuroglycopenic symptoms; increase monitoring. |
| Corticosteroids, sympathomimetics, some antipsychotics | Increase insulin requirements and hyperglycaemia. | Temporary dose adjustment and closer monitoring. |
| ACE inhibitors, alcohol, salicylates and some antimicrobials | May increase hypoglycaemia risk in some patients. | Review glucose after starting/stopping the interacting drug. |
| GLP-1 agonist + insulin/sulfonylurea | Additive hypoglycaemia and delayed gastric emptying. | Reduce secretagogue/insulin when appropriate; monitor during titration. |
| Insulin + potassium-lowering diuretic | Hypokalaemia may worsen during insulin treatment. | Check potassium in acutely ill patients. |
13. Clinical cases
Case 1 — new type 1 diabetes with ketosis
A young adult has polyuria, vomiting, glucose 28 mmol/L, positive ketones and pH 7.18. This is DKA until proven otherwise. Begin fluids, potassium-guided IV regular insulin and trigger treatment; do not use subcutaneous long-acting insulin alone as the emergency treatment.
Case 2 — insulin pen concentration error
A patient using U-300 glargine draws the dose into a U-100 syringe and becomes drowsy. Treat the hypoglycaemia, observe for prolonged recurrence and report the medication error. Teach that concentrated pens must deliver units through their dedicated device and must not be converted by volume.
Case 3 — pump failure
A pump user has glucose 24 mmol/L, nausea and moderate ketones. Check the cannula, infusion set and pump, but do not wait for troubleshooting if ketones or acidosis are present. Give prescribed backup rapid insulin, fluids and urgent DKA assessment.
Case 4 — GLP-1 agonist abdominal pain
A patient taking semaglutide has persistent severe epigastric pain radiating to the back and vomiting. Stop the medicine, assess lipase, liver tests, hydration and imaging indications, and manage possible pancreatitis or gallbladder disease urgently.
Case 5 — fasting before surgery
A patient with type 1 diabetes is told to stop all insulin before surgery. Correct the plan: basal insulin is usually continued with a dose adjustment and IV glucose/insulin or a variable-rate infusion may be used. Coordinate with anaesthesia and the surgical protocol to prevent DKA.
14. High-yield revision points
- Insulin is always required in type 1 diabetes and is the emergency treatment for DKA.
- Rapid analogues are given immediately before or just after eating; regular insulin is usually given about 30 minutes before meals and is the common IV insulin.
- NPH is cloudy and peaks; glargine, detemir and degludec are basal preparations and should not be mixed casually.
- Basal insulin is usually started in type 2 diabetes at 10 units daily or about 0.1–0.2 units/kg/day, then titrated from fasting glucose.
- U-40, U-100 and concentrated insulins are not interchangeable by syringe volume.
- Insulin causes hypoglycaemia, weight gain, lipodystrophy and potassium shift; rotate sites and monitor potassium in emergencies.
- GLP-1 agonists lower glucose and weight with low hypoglycaemia risk alone but can cause gastrointestinal intolerance, dehydration, pancreatitis and gallbladder disease.
- Never stop basal insulin in type 1 diabetes during illness without a replacement plan.
15. Sources and further reading
- Supplied SlideShare: Injectable therapy in diabetes mellitus management.
- DailyMed: insulin lispro.
- DailyMed: insulin aspart.
- DailyMed: insulin glargine.
- DailyMed: insulin degludec.
- DailyMed: liraglutide injection.
- DailyMed current product labels.
This is an educational resource for supervised clinical learning. Insulin is a high-alert medicine. Confirm product name, concentration, units, timing, patient identity and local protocol before every administration.
