UKPDS-26 - SULFONYLUREA FAILURE IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS OVER 6 YEARS

Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphon ylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulp honylureas, we report on the responses in 1305 patients with newly dia gnosed Type 2 DM randomly allocated to therapy with either chlorpropam ide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). The se patients were initially treated by diet for 3 months and had a fast ing plasma glucose >6 mmol l(-1) mean age 53 (SD 9) years; BMI 26.8 (S D 5.0) kg m(-2); and median lasting plasma glucose 9.1 (7.6-12.5 quart iles) mmol l(-1). If their lasting plasma glucose subsequently rose ab ove 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additi onal hypoglycaemic therapy was given: metformin, ultratard insulin, an d soluble insulin as required. By 6 years, 44 % had required additiona l therapy. Of those randomized to glibenclamide, 48 % required additio nal therapy by 6 years, compared with 40 % of those allocated to chlor propamide (p < 0.01). Sixty-one per cent, 39 %, and 23 %, respectively , of patients with fasting plasma glucose greater than or equal to 10. 0 mmol l(-1), greater than or equal to 7.8 mmol l(-1) to <10.0 mmol l( -1) and <7.8 mmol l(-1) at randomization required additional therapy ( p < 0.001). In the initial 3 years, non-obese subjects (BMI <30 kg m(- 2)) were more likely to require additional therapy than obese patients (BMI greater than or equal to 30 kg m(-2)) (43 % vs 53 % at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower f unction were more likely to fail (p < 0.0001). Thus sulphonylureas fai l as a therapeutic agent at rates which are dependent both on the phen otype at presentation and perhaps on the agent used initially. Higher failure rates were found in those with higher glucose concentrations, those who were younger, those with lower beta-cell reserve and those r andomized to glibenclamide compared with chlorpropamide. (C) 1998 John Wiley & Sons, Ltd.