United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years

BMJ. 1995 Jan 14;310(6972):83-8.

Abstract

Objective: To assess the relative efficacy of treatments for non-insulin dependent diabetes over three years from diagnosis.

Design: Multicentre, randomised, controlled trial allocating patients to treatment with diet alone or additional chlorpropamide, glibenclamide, insulin, or metformin (if obese) to achieve fasting plasma glucose concentrations < or = 6 mmol/l.

Setting: Outpatient diabetic clinics in 15 British hospitals.

Subjects: 2520 subjects who, after a three month dietary run in period, had fasting plasma glucose concentrations of 6.1-14.9 mmol/l but no hyperglycaemic symptoms.

Main outcome measures: Fasting plasma glucose, glycated haemoglobin, and fasting plasma insulin concentrations; body weight; compliance; and hypoglycaemia.

Results: Median fasting plasma glucose concentrations were significantly lower at three years in patients allocated to chlorpropamide, glibenclamide, or insulin rather than diet alone (7.0, 7.6, 7.4, and 9.0 mmol/l respectively; P < 0.001) with lower mean glycated haemoglobin values (6.8%, 6.9%, 7.0%, and 7.6%, respectively; P < 0.001). Mean body weight increased significantly with chlorpropamide, glibenclamide, and insulin but not diet (by 3.5, 4.8, 4.8, and 1.7 kg; P < 0.001). A similar pattern was seen for mean fasting plasma insulin concentration (by 0.9, 1.2, 2.4, and -0.1 mU/l; P < 0.001). In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P < 0.001). More hypoglycaemic episodes occurred with sulphonylurea or insulin than with diet or metformin.

Conclusion: The drugs had similar glucose lowering efficacy, although most patients remained hyperglycaemic. Long term follow up is required to determine the risk-benefit ratio of the glycaemic improvement, side effects, changes in body weight, and plasma insulin concentration.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Body Weight / physiology
  • Chlorpropamide / therapeutic use
  • Diabetes Mellitus / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / therapy*
  • Female
  • Follow-Up Studies
  • Glyburide / therapeutic use
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin / blood
  • Insulin / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Obesity
  • Patient Compliance
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Sulfonylurea Compounds
  • Metformin
  • Glyburide
  • Chlorpropamide