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UKPDS 34: study design

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  1. Conventional therapy Diet alone (n = 411) Metformin (n = 342) Insulin(n = 409) Chlorpropamide(n = 265) Glibenclamide(n = 277) UKPDS 34: study design Overweight patientsin 15 centres (n = 1704) Randomisation Intensive therapy UKPDS 34: Lancet 1998;352:854–65

  2. UKPDS 34: participant characteristics UKPDS 34: Lancet 1998;352:854–65

  3. Insulin Metformin 10 Chlorpropamide Conventional Glibenclamide 9 8 7 6 0 0 3 6 9 12 15 Years from randomisation UKPDS 34: intensive therapy reduced HbA1c Median HbA1c (%) Dashed lines indicate patients followed for 10 yearsSolid lines indicate all patients assigned to regimen Adapted from: Lancet 1998;352:854–65

  4. 0 10 20 30 40 50 UKPDS 34: relative risk reduction with metformin vs conventional treatment All-cause mortality Diabetes death Any diabetes endpoint Stroke MI Relative risk reduction for metformin treatment (%) ** * * * * p < 0.05 ** p < 0.01 UKPDS 34: Lancet 1998;352:854–65

  5. Any diabetes endpoint All-cause mortality Diabetes death Stroke MI 20 10 Intensive SUs or insulin 0 10 Metformin 20 30 40 ** * 50 * UKPDS 34: relative risk reduction with metformin or SUs/insulin Risk reduction relative to conventional treatment (%) * p < 0.05 ** p < 0.01 UKPDS 34: Lancet 1998;352:854–65

  6. Insulin Metformin Chlorpropamide Conventional 10 Glibenclamide 7.5 5 2.5 0 0 3 6 9 12 15 Years from randomisation UKPDS 34: metformin therapy was not associated with weight gain Mean change (kg) Baseline = 85 kg Dashed lines indicate patients followed for 10 yearsSolid lines indicate all patients assigned to regimen Adapted from: Lancet 1998;352:854–65

  7. Insulin Metformin Chlorpropamide Conventional Glibenclamide 60 10 Any episodes Major episodes 50 8 40 6 30 4 20 2 10 0 0 0 3 6 9 12 15 0 3 6 9 12 15 UKPDS 34: metformin was associated with less hypoglycaemia than insulin or SUs Patients with at least 1 episode (%) Years from randomisation Adapted from: Lancet 1998;352:854–65

  8. Side effects of metformin • Gastrointestinal: • diarrhoea • nausea • vomiting • bloating • Anorexia • Contraindicated in patients with: • cardiovascular impairments • renal dysfunction • hepatic dysfunction

  9. Economic analysis - UKPDS • “Our economic analysis shows that the additional costs of intensive management are largely offset by significant reductions in the costs of treating complications of diabetes.” UKPDS 41 BMJ 2000;320:1373–78