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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

Correspondence to: UK Prospective Diabetes Study, Diabetes Research Laboratories, Radcliffe Infirmary, Oxford OX2 6HE.

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 </=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.

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Rapid Responses:

Read all Rapid Responses

Randomization the powerful technique mentioned in the UKPDS13 will minimize initial sample bias but will not eliminate it.

Arya K Kumarasena
bmj.com, 14 Feb 2008 [Full text]