Lithium can cause insulin resistance and hyperglycaemia, making regular insulin doses unstable; intensified glucose monitoring on the combination.
Lithium alters glucose metabolism and insulin sensitivity (hyperglycaemia described in lithium entries and Prontuário); short-acting regular insulin exposes fluctuations.
Capillary glucose, serum lithium, weight, polyuria/polydipsia.
New polyuria and polydipsia (hyper) or sweating/confusion (hypo).
Monitor capillary glucose and HbA1c; adjust insulin doses if fasting glucose rises; assess serum lithium in decompensation.
INFARMED Prontuário Terapêutico (11th ed., 2012), Lithium Carbonate entry; DailyMed — Lithium Carbonate and Humulin R labels: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b839ff4b-f62d-41ab-a823-550a756d58ec
Metoprolol masks the adrenergic symptoms of hypoglycaemia (tachycardia, tremor) and may prolong insulin-induced hypoglycaemia.
Beta-blockade blunts the compensatory adrenergic response (tachycardia, tremor) and blocks hepatic β2 (glycogenolysis); Prontuário 8.4.1: "special concern with insulin administration in patients ... on beta-adrenergic blockers".
Capillary glucose, atypical heart rate, neurological status.
Sudden sweating without tachycardia, confusion, loss of consciousness (unrecognised hypoglycaemia).
Reinforce education on "neuroglycopenic" hypoglycaemia (persistent sweating, confusion); more frequent capillary glucose; consider cardioselective beta-blocker at minimum dose.
INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4.1 Insulins (p. 358) — beta-adrenergic blockers; DailyMed — Humulin R (human regular insulin) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921
Non-selective propranolol blocks hepatic β2 glycogenolysis and masks the warning symptoms of insulin-induced hypoglycaemia, potentially worsening and prolonging episodes.
Hepatic β2 blockade reduces compensatory glycogenolysis; cardiac β1 blockade removes the tachycardia warning (Prontuário 8.4.1; insulin label: agents increasing hypoglycaemia risk).
Capillary glucose, neurological status, sweating.
Sudden confusion, strange behaviour, loss of consciousness.
Monitor capillary glucose; prefer a cardioselective beta-blocker (metoprolol/bisoprolol) if needed; teach recognition of hypoglycaemia "without tachycardia".
DailyMed — Humulin R (regular insulin) and Inderal (propranolol) labels, Drug Interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921; INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4.1.
Combining regular insulin with metformin is intentional therapy in T2DM, but requires dose titration of both: additive hypoglycaemia risk when doses are not titrated.
Metformin ↓ hepatic glucose production and insulin ↑ peripheral uptake; the sum requires recalibrating doses and meals (label/EMC: adjust insulin dose).
Capillary glucose (fasting and post-prandial), 3-month HbA1c, renal function.
Sweating, confusion, cramps, lactic acidosis (rare, metformin).
Gradual insulin titration when metformin is continued; capillary/continuous glucose; hypoglycaemia education; review renal function (metformin).
DailyMed — Metformin HCl Tablet [Glenmark] and Humulin R labels: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0ef9de1a-b786-4b6c-a250-3f5ac532b16a; INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4/8.5.
Alcohol inhibits hepatic gluconeogenesis and potentiates insulin-induced hypoglycaemia; the risk is highest on an empty stomach.
Avoid alcohol, especially while fasting; if consumed, take it with food and monitor blood glucose (site monograph).
Prontuário Terapêutico INFARMED, 8.4.1 Insulins: "special concern … alcoholics"; site monograph (avoid alcohol).
Alcohol potentiates insulin-induced hypoglycaemia (inhibits hepatic gluconeogenesis); the Prontuário flags "special concern" in alcoholics.
Advise avoiding alcohol while fasting; reinforce glucose self-monitoring and hypoglycaemia awareness education.
Prontuário Terapêutico INFARMED, 8.4 Insulins: "special concern... alcoholics".
Hypoglycaemia in patients with coronary or cerebrovascular disease can precipitate ischaemia/arrhythmia — the Prontuário requires "special concern".
Less aggressive glycaemic targets; avoid documented hypoglycaemia; enhanced surveillance.
Prontuário Terapêutico INFARMED, 8.4: "individuals with coronary or cerebrovascular disease".
Insulin is the ANTIDIABETIC OF CHOICE in pregnancy (it does not cross the placenta in relevant amounts and controls maternal glycaemia). Annex 1 records "insulin requirements should be assessed frequently by a diabetologist... with insulin lispro there is no increase in congenital malformations. Avoid inhaled insulins." Requirements rise in the 2nd–3rd trimesters and fall sharply after delivery.
Compatible and indicated; adjust requirements frequently (NPH/regular or lispro/aspart analogues); specialised obstetric surveillance (malformations are linked to maternal hyperglycaemia, not insulin).
Compatible: "present in milk in amounts too small to be harmful" (Annex 2, l. 42790); insulin is degraded in the infant gut.
Prontuário Terapêutico INFARMED — Annex 1: "Insulins" (l. 40605, 40619-23); Annex 2 (l. 42790). EMC-UK (MHRA) — Insulin Human SmPC (Actrapid): https://www.medicines.org.uk/emc/product/1221/smpc.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
↓ blood glucose via ↑ peripheral glucose uptake and ↓ hepatic production; onset 30 min, peak 1.5–3.5 h, duration 7–8 h (SC).
Insulin receptor agonist (RTK): phosphorylates IRS substrates → PI3K/Akt → GLUT4 membrane translocation; also activates the MAPK (mitogenic) pathway.
SC: rapid and variable absorption (peak 1.5–3.5 h; influenced by dose, site, blood flow); IV: 100% bioavailability, immediate action (ketoacidosis).
Proteolytic degradation by insulin-degrading enzyme (IDE) in liver, kidney and muscle; ~ 50% cleared by endogenous hepatic first pass (not applicable to SC exogenous).
~ 5–10 min (IV); ~ 1–1.5 h (SC; 7–8 h duration of effect from absorption).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
