Synopsis
Select and monitor established type 2 diabetes medicines by mechanism, kidney function, hypoglycaemia, heart failure, weight and adverse-effect risk.
- Metformin reduces hepatic glucose production, is weight neutral or modestly weight reducing, and rarely causes hypoglycaemia alone; gastrointestinal intolerance and kidney function limit use.
- Start metformin gradually with food and consider modified-release formulation when gastrointestinal effects prevent adherence; review renal thresholds against current BNF and NICE guidance.
- Metformin commonly lowers vitamin B12 over time, so investigate anaemia, neuropathy, glossitis or cognitive symptoms and consider periodic testing in those at risk.
- Sulfonylureas increase pancreatic insulin release independent of current glucose and therefore cause hypoglycaemia and weight gain, especially with missed meals or reduced renal clearance.
- Gliclazide is commonly used in the UK, but dose and suitability depend on renal and hepatic function, occupation, meal reliability and hypoglycaemia risk.
- Pioglitazone improves insulin sensitivity but can cause fluid retention, weight gain and fractures; avoid in heart failure and active or previous bladder cancer or unexplained haematuria.
- Review pioglitazone response and safety after several months and stop it when there is no meaningful benefit rather than continuing by inertia.
- The February 2026 NICE type 2 algorithm is phenotype-led; do not reproduce an older step ladder from memory when choosing or combining these medicines.
- All three classes need a sick-day or perioperative plan; insulin-deficient symptoms and marked hyperglycaemia should prompt insulin assessment instead of stacking tablets slowly.
Key red flags
Acute kidney injury, severe dehydration, tissue hypoxia, sepsis or hepatic failure reduces lactate clearance and should trigger temporary withdrawal and urgent physiological assessment.
Sweating, tremor, confusion, focal neurology, seizure or coma may recur because drug action outlasts oral glucose, particularly in older adults and renal impairment.
New oedema, rapid weight gain, orthopnoea or breathlessness suggests fluid retention or heart failure and requires prompt medicine cessation and cardiac assessment.
Weight loss, ketosis, catabolic symptoms or very high symptomatic glucose despite tablets suggests marked beta-cell failure or misclassified diabetes and needs urgent insulin-capable review.
Investigation priorities
Measure effect and detect excessive or inadequate treatment.
Management branches
Metformin selected within the current NICE phenotype-based regimen.
- Confirm kidney function, acute illness, alcohol exposure, tissue-hypoxia risk and pregnancy context; explain gastrointestinal effects and sick-day interruption before the first prescription.
- Start low with food and increase gradually using immediate or modified release according to tolerance and the current formulary, rather than beginning at the maximum dose.
- Review HbA1c and gastrointestinal burden, check eGFR at the required interval and investigate B12 when symptoms or risk factors arise.
- Temporarily stop during significant dehydration, acute kidney injury, hypoxia or protocol-defined contrast and perioperative situations, restarting after clinical and renal recovery is confirmed.