Pharmacology chapters
Insulin and oral antidiabetic drugs
How insulin preparations differ in onset and duration, how to treat diabetic ketoacidosis and hypoglycaemia, and how each class of non-insulin diabetes drug works (metformin, sulphonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists, pioglitazone, acarbose) with its key adverse effects.
- Insulin types: rapid-acting analogues (lispro, aspart: inject with meals), short-acting soluble/regular (the only type given IV, used in DKA), intermediate NPH (isophane) and long-acting basal analogues (glargine, detemir, degludec); the main adverse effect is hypoglycaemia, plus weight gain and lipohypertrophy at injection sites.
- Metformin (first-line in type 2) lowers hepatic glucose output, causes no hypoglycaemia or weight gain, but causes gut upset, vitamin B12 deficiency and rarely lactic acidosis (avoid in severe renal failure, hypoxia, before iodinated contrast in kidney impairment); sulphonylureas (gliclazide, glimepiride, glibenclamide) close KATP channels on β cells → insulin release → hypoglycaemia and weight gain.
- SGLT2 inhibitors (empagliflozin, dapagliflozin) cause glycosuria → genital fungal infections, euglycaemic DKA, but protect heart and kidneys; GLP-1 agonists (liraglutide, semaglutide: injected) cause weight loss and nausea; DPP-4 inhibitors (sitagliptin) are weight-neutral; pioglitazone (PPAR-γ) causes fluid retention (avoid in heart failure) and fractures.
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Insulin
Actions: acts on a tyrosine kinase receptor: increases glucose uptake into muscle and fat (GLUT4), glycogen synthesis, fat and protein synthesis; reduces gluconeogenesis, glycogenolysis, lipolysis and ketone formation; drives potassium into cells.
Types of insulin
| Type | Examples | Onset | Peak | Duration | Use |
|---|---|---|---|---|---|
| Rapid-acting analogues | Lispro, aspart, glulisine | About 15 min | About 1 h | 3–5 h | With meals (bolus); pumps |
| Short-acting (soluble, regular) | Human soluble insulin | About 30 min | 2–4 h | Up to about 8 h | 30 minutes before meals; IV in DKA, hyperkalaemia, peri-operative |
| Intermediate | NPH (isophane) | 1–2 h | 4–8 h | 12–18 h | Basal, often twice daily; pre-mixed 70/30 |
| Long-acting analogues | Glargine, detemir, degludec | 1–2 h | Little or no peak | About 24 h (degludec longer) | Basal once daily |
Times are approximate and vary with dose and injection site.
Only soluble (regular) insulin is routinely given intravenously.
Regimens: basal-bolus (long-acting once daily + rapid-acting with meals) for type 1; twice-daily pre-mixed; basal insulin added to tablets in type 2.
Adverse effects: hypoglycaemia (commonest and most important), weight gain, lipohypertrophy (rotate sites), hypokalaemia (IV), allergy (rare).
Hypoglycaemia (blood glucose below about 4 mmol/L)
- Symptoms: sweating, tremor, palpitations, hunger (adrenergic); confusion, odd behaviour, seizures, coma (neuroglycopenic). β blockers can mask the warning symptoms.
- Conscious and able to swallow: 15–20 g fast-acting glucose (glucose tablets, juice), recheck after 10–15 minutes, then a longer-acting carbohydrate.
- Unconscious: IV glucose (for example 100 mL of 20% or 150–200 mL of 10% in adults) or IM glucagon 1 mg (less effective in alcohol excess or starvation, when liver glycogen is low).
- Sulphonylurea-induced hypoglycaemia can be prolonged: admit and observe.
Diabetic ketoacidosis (DKA)
Insulin deficiency → hyperglycaemia, ketosis and metabolic acidosis, with dehydration and total-body potassium loss.
- IV fluids first: 0.9% sodium chloride (large deficit).
- Fixed-rate IV insulin infusion: 0.1 unit/kg/hour of soluble insulin. Continue basal long-acting insulin.
- Potassium: add to fluids once potassium is below the upper normal range and urine is passing (insulin drives K⁺ into cells → hypokalaemia risk).
- Add 10% glucose when blood glucose falls below about 14 mmol/L, so insulin can continue until ketones clear.
- Treat the cause (infection, missed insulin); watch for cerebral oedema (especially children) and hypoglycaemia.
Fixed-rate IV insulin = 0.1 unit per kg per hour
70 kg patient: 0.1 × 70 = 7 units per hour
Typical syringe: 50 units soluble insulin in 50 mL saline = 1 unit/mL
Pump rate = 7 mL per hour
Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻)
Na 135, Cl 98, HCO₃ 8 → 135 − (98 + 8) = 29 mmol/L (raised; normal about 8–14)
Follows UK Joint British Diabetes Societies teaching; use your hospital protocol.
Non-insulin drugs for type 2 diabetes
| Class | Examples | Mechanism | Main adverse effects | Notes |
|---|---|---|---|---|
| Biguanide | Metformin | ↓ hepatic glucose production; ↑ insulin sensitivity (activates AMP kinase) | Gut upset (diarrhoea), vitamin B12 deficiency, rare lactic acidosis | First-line; no hypoglycaemia, weight-neutral or loss; avoid in severe renal impairment, liver failure, hypoxia, shock; pause around iodinated contrast if kidney function poor; used in PCOS and gestational diabetes |
| Sulphonylureas | Gliclazide, glimepiride, glibenclamide | Close ATP-sensitive K⁺ channels on β cells → depolarisation → insulin release | Hypoglycaemia (glibenclamide long-acting: worst in elderly and renal failure), weight gain | Need working β cells; interactions raise risk |
| Meglitinides | Repaglinide, nateglinide | Same as sulphonylureas, short-acting | Hypoglycaemia (less) | Taken with meals |
| Thiazolidinediones | Pioglitazone | Activate PPAR-γ → ↑ insulin sensitivity in fat and muscle | Fluid retention (avoid in heart failure), weight gain, fractures, bladder cancer concern, liver toxicity (older drug troglitazone) | No hypoglycaemia alone |
| DPP-4 inhibitors ("gliptins") | Sitagliptin, vildagliptin, linagliptin | Block breakdown of incretins (GLP-1, GIP) → glucose-dependent insulin release, less glucagon | Generally well tolerated; rare pancreatitis | Weight-neutral; low hypoglycaemia risk |
| GLP-1 receptor agonists | Liraglutide, semaglutide, exenatide, dulaglutide | Mimic GLP-1: ↑ insulin (glucose-dependent), ↓ glucagon, slow gastric emptying, ↓ appetite | Nausea, vomiting; pancreatitis risk | Weight loss; cardiovascular benefit (some); injected (oral semaglutide exists) |
| SGLT2 inhibitors ("gliflozins") | Empagliflozin, dapagliflozin, canagliflozin | Block glucose reabsorption in the proximal tubule → glycosuria | Genital fungal infections, UTIs, volume depletion, euglycaemic DKA, Fournier gangrene (rare) | Heart failure and kidney protection; weight loss |
| α-glucosidase inhibitors | Acarbose | Slow carbohydrate digestion in the gut | Flatulence, diarrhoea | Treat hypoglycaemia with glucose, not sucrose |
No hypoglycaemia when used alone: metformin, pioglitazone, DPP-4 inhibitors, GLP-1 agonists, SGLT2 inhibitors, acarbose. Hypoglycaemia: insulin, sulphonylureas, meglitinides.
Weight: gain with insulin, sulphonylureas, pioglitazone; loss with GLP-1 agonists, SGLT2 inhibitors, metformin (slight).
Diabetes in pregnancy
- Insulin is the standard; metformin is also used; glibenclamide in some settings.
- Most other oral drugs are avoided.
- Aim for tight glucose control before conception and give higher-dose folic acid.
Expect: insulin types and which is given IV, hypoglycaemia treatment and glucagon, DKA management (fluids, 0.1 unit/kg/h, potassium), metformin mechanism and adverse effects (lactic acidosis, B12), sulphonylurea mechanism (KATP) and hypoglycaemia, pioglitazone and heart failure, DPP-4, GLP-1 and SGLT2 drugs with their characteristic effects, drugs that do and do not cause hypoglycaemia or weight gain, and diabetes drugs in pregnancy.
Quick revision
- Rapid (lispro, aspart), short (soluble: IV), intermediate (NPH), long (glargine, degludec).
- Insulin: hypoglycaemia, weight gain, lipohypertrophy.
- DKA: fluids, fixed-rate insulin 0.1 unit/kg/h, potassium, add glucose later.
- Metformin: first-line; no hypoglycaemia; B12 deficiency; lactic acidosis.
- Sulphonylureas: KATP closure; hypoglycaemia, weight gain.
- Pioglitazone: PPAR-γ; fluid retention, heart failure.
- SGLT2: glycosuria, thrush, euglycaemic DKA. GLP-1: weight loss, nausea.
Written by The House Job from standard pharmacology references (Katzung's Basic and Clinical Pharmacology).
FAQ
Which insulin can be given intravenously?
Soluble (regular, short-acting) insulin.
How do sulphonylureas work?
They close ATP-sensitive potassium channels on pancreatic beta cells, which depolarises them and releases insulin.
Why can metformin cause lactic acidosis?
It reduces the liver's use of lactate for glucose production; the risk rises when the drug accumulates (kidney failure) or when lactate production is high (hypoxia, shock).
What are the main adverse effects of SGLT2 inhibitors?
Genital fungal infections, urinary infections, dehydration and euglycaemic diabetic ketoacidosis.