RESUMO
We review pharmacological/prescribing principles relating to metformin according to our mnemonic framework: 'BRAINS & AIMS' (Benefits, Risks, Adverse Effects, Interactions, Necessary prophylaxis, Susceptibilities, Administering, Informing, Monitoring and Stopping): Benefits: Metformin's licensed uses: Type 2 diabetes mellitus (T2DM) treatment, reduction in risk or delay of onset. No clear evidence metformin influences patient-important outcomes [Cochrane Review (2020) of 18 RCTs (n = 10 680)]. Risks: Inexpensive, essential WHO list drug; use contraindicated/not tolerated in 15%: for example, contraindication: lactic acidosis in renal impairment (eGFR <30 mL/min/1.73 m2 ). Adverse effects: Common gastrointestinal (GI) side effects are dose-related and include abdominal pain, decreased appetite, diarrhoea (usually transient), nausea and vomiting, altered taste; vitamin B12 deficiency. Rare: acute metabolic acidosis (lactic acidosis/diabetic ketoacidosis). Interactions (pharmacokinetic) occur with drugs impairing renal function and hence metformin excretion, and drugs inhibiting organic cation transporter 1 or 2 (OCT1, OCT2), and/or multidrug and toxin extrusion protein 1 (MATE1/2-K), such as cimetidine, ranolazine, trimethoprim and verapamil, and inducers such as rifampicin. The risk of hypoglycaemia may increase when metformin is used in combination with other medications for diabetes (pharmacodynamic interaction). Necessary prophylaxis: Detect/treat vitamin B12 deficiency. Susceptible groups: Elderly/renal/liver impairment (lactic acidosis); safe in pregnancy/breastfeeding. Administering: Initially 500 mg once daily (morning) with breakfast; titrate only after 1 week. Informing (relevant BRAINS & A(I)MS principles). Monitoring: Renal function beforehand, and 6-12 monthly, HbA1c 3-6 monthly until controlled. Serum vitamin B12 levels if deficiency is suspected/risk factors for. Stopping: Encourage patients to continue medication, unless deteriorating renal/liver function. Reasons for deprescribing: no harms from stopping suddenly.
