Metformin

Mechanism

Fluoroquinolones disturb glucose homeostasis — they can cause both hypoglycaemia (especially in older patients on glucose-lowering therapy) and hyperglycaemia. The mechanism involves pancreatic beta-cell effects.

Symptoms

Hypoglycaemia: sweating, tremor, hunger, confusion at glucose below 3.9 mmol/L. Hyperglycaemia: thirst, polyuria, fatigue.

Management

For short ciprofloxacin courses (5–7 days) on metformin, intensify glucose self-monitoring (twice daily) for the first week. In older patients and diabetics on insulin or sulfonylureas, choose an alternative antibiotic (cephalosporin, amoxicillin-clavulanate).

Mechanism

Metformin suppresses calcium-dependent absorption of the B12-intrinsic factor complex in the terminal ileum. With over 4 years of therapy, clinically significant B12 deficiency is reported in 10–30% of patients.

Symptoms

Fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline. Develops over 2–4 years of unrecognised therapy.

Management

On long-term metformin, check B12 yearly. If it falls below 200 pg/mL, give cyanocobalamin 500–1000 mcg/day orally or 1000 mcg/week intramuscularly (in significant neuropathy). Supplementation does not cancel the metformin indication.

Mechanism

Dexamethasone stimulates gluconeogenesis and reduces tissue insulin sensitivity. The glycaemic effect is stronger than with prednisolone due to long half-life and high potency.

Symptoms

Return of thirst and polyuria, rising fasting glucose, fatigue. In type 2 diabetes, possible decompensation with HbA1c rise of 0.5–1.5%.

Management

For short dexamethasone pulses (1–3 days, e.g. cerebral oedema or post-chemotherapy), no metformin adjustment needed — transient hyperglycaemia is tolerated. For long-term therapy, increase metformin or add long-acting insulin. Check glucose twice daily in the first week.

Mechanism

ACE inhibitors improve tissue insulin sensitivity and potentiate metformin's glucose-lowering effect. They do not cause hypoglycaemia alone but lower the threshold on insulin or sulfonylureas.

Symptoms

Signs of hypoglycaemia: sweating, tremor, hunger, tachycardia, confusion. Symptoms appear at glucose below 3.9 mmol/L.

Management

On metformin alone, no dose adjustment needed. In patients on insulin or sulfonylureas, intensify glucose self-monitoring for the first 2 weeks after starting enalapril. The effect is helpful in type 2 diabetes with arterial hypertension.

Mechanism

Thiazide diuretics reduce glycaemic control via hypokalaemia-driven suppression of insulin secretion. HbA1c may rise by 0.3–0.5%, especially in the first 6 months.

Symptoms

Return of thirst and polyuria, rising fasting glucose, signs of worsening control. Symptoms are typically mild.

Management

Check fasting glucose and HbA1c 3 months after starting hydrochlorothiazide. If HbA1c rises, increase metformin or add another glucose-lowering agent. Potassium every 6 months. In overt diabetes decompensation, alternatives: indapamide (less metabolic effect) or an SGLT-2 inhibitor.

Mechanism

ARBs, like ACE inhibitors, improve tissue insulin sensitivity. In patients on insulin or sulfonylureas with metformin, the glucose-lowering effect may be amplified.

Symptoms

Signs of hypoglycaemia: sweating, tremor, hunger, tachycardia, confusion. Symptoms appear at glucose below 3.9 mmol/L.

Management

On metformin alone, no dose adjustment needed. On insulin or sulfonylureas, intensify glucose self-monitoring for the first 2 weeks after starting losartan. The effect is helpful in type 2 diabetes with arterial hypertension.