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UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group.
Diabet Med 1998; 15(4):297-303DM

Abstract

Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to therapy with either chlorpropamide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). These patients were initially treated by diet for 3 months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years; BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5 quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble insulin as required. By 6 years, 44% had required additional therapy. Of those randomized to glibenclamide, 48% required additional therapy by 6 years, compared with 40% of those allocated to chlorpropamide (p < 0.01). Sixty-one per cent, 39%, and 23%, respectively, of patients with fasting plasma glucose > or = 10.0 mmol l(-1), > or = 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 > or = 30 kg m(-2)) (43% vs 53% at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower function were more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent at rates which are dependent both on the phenotype 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 randomized to glibenclamide compared with chlorpropamide.

Authors+Show Affiliations

Oxford Diabetes & Endocrinology Centre, The Radcliffe Infirmary NHS Trust, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9585394

Citation

Matthews, D R., et al. "UKPDS 26: Sulphonylurea Failure in Non-insulin-dependent Diabetic Patients Over Six Years. UK Prospective Diabetes Study (UKPDS) Group." Diabetic Medicine : a Journal of the British Diabetic Association, vol. 15, no. 4, 1998, pp. 297-303.
Matthews DR, Cull CA, Stratton IM, et al. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998;15(4):297-303.
Matthews, D. R., Cull, C. A., Stratton, I. M., Holman, R. R., & Turner, R. C. (1998). UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabetic Medicine : a Journal of the British Diabetic Association, 15(4), pp. 297-303.
Matthews DR, et al. UKPDS 26: Sulphonylurea Failure in Non-insulin-dependent Diabetic Patients Over Six Years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998;15(4):297-303. PubMed PMID: 9585394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. AU - Matthews,D R, AU - Cull,C A, AU - Stratton,I M, AU - Holman,R R, AU - Turner,R C, PY - 1998/5/19/pubmed PY - 1998/5/19/medline PY - 1998/5/19/entrez SP - 297 EP - 303 JF - Diabetic medicine : a journal of the British Diabetic Association JO - Diabet. Med. VL - 15 IS - 4 N2 - Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to therapy with either chlorpropamide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). These patients were initially treated by diet for 3 months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years; BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5 quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble insulin as required. By 6 years, 44% had required additional therapy. Of those randomized to glibenclamide, 48% required additional therapy by 6 years, compared with 40% of those allocated to chlorpropamide (p < 0.01). Sixty-one per cent, 39%, and 23%, respectively, of patients with fasting plasma glucose > or = 10.0 mmol l(-1), > or = 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 > or = 30 kg m(-2)) (43% vs 53% at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower function were more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent at rates which are dependent both on the phenotype 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 randomized to glibenclamide compared with chlorpropamide. SN - 0742-3071 UR - https://www.unboundmedicine.com/medline/citation/9585394/UKPDS_26:_Sulphonylurea_failure_in_non_insulin_dependent_diabetic_patients_over_six_years__UK_Prospective_Diabetes_Study__UKPDS__Group_ L2 - https://ClinicalTrials.gov/search/term=9585394 [PUBMED-IDS] DB - PRIME DP - Unbound Medicine ER -