United Kingdom Prospective Diabetes Study 24: A 6-Year, Randomized, Controlled Trial Comparing Sulfonylurea, Insulin, and Metformin Therapy in Patients with Newly Diagnosed Type 2 Diabetes That Could Not Be Controlled with Diet Therapy
Authors: A Wright, C Cull, R Holman, R Turner, L Murchison, AD Wright, N Oakley, E Kohner, R Hayes, J Scarpello, D Hadden, AG Spathis, J Yudkin, R Greenwood, L Borthwick, J Day, R Newton, C Fox, R Paisey, J Roland, D Humphriss, I Peacock, A Boulton, T Dornan, F Burden, J Tooke, United Kingdom Prospective Diabet Study Grp
Journal: Annals of Internal Medicine (1998)

Articles1 February 1998United Kingdom Prospective Diabetes Study 24: A 6-Year, Randomized, Controlled Trial Comparing Sulfonylurea, Insulin, and Metformin Therapy in Patients with Newly Diagnosed Type 2 Diabetes That Could Not Be Controlled with Diet TherapyAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-3-199802010-00001 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AbstractBackground:Uncertainty exists about the suitability of oral hypoglycemic drugs and insulin therapy for patients with newly diagnosed type 2 diabetes.Objective:To assess and compare response to sulfonylurea, insulin, or metformin over 6 years in patients with newly diagnosed type 2 diabetes in whom disease could and could not be controlled with diet therapy alone.Design:Multicenter, randomized, controlled trial.Setting:Outpatient diabetes clinics of 15 hospitals in the United Kingdom.Intervention:Sulfonylurea (chlorpropamide or glyburide), insulin, or metformin (if patients were obese).Patients:458 patients with newly diagnosed type 2 diabetes that could not be controlled with diet and had hyperglycemic symptoms or fasting plasma glucose levels greater than 15 mmol/L during the initial 3 months of diet therapy (primary diet failure group) and 1620 patients in whom disease was controlled by diet therapy and who had fasting plasma glucose levels of 6 to 15 mmol/L and no hyperglycemic symptoms while receiving diet therapy alone.Measurements:Fasting plasma levels of glucose and insulin, hemoglobin A1c concentrations, body weight, and therapy required.Results:Compared with the diet-controlled group, the primary diet failure group was younger and less obese and had more retinopathy, lower fasting plasma insulin levels, and reduced β-cell function. At 6 years, patients allocated to insulin had lower fasting plasma glucose levels than did patients allocated to oral agents, but hemoglobin A1c concentrations were similar. Forty-eight percent (95% CI, 37% to 58%) of patients in the primary diet failure group maintained hemoglobin A1c concentrations less than 0.08. By 6 years, 51% of patients (CI, 42% to 62%) allocated to ultralente insulin required additional short-acting insulin and 66% of patients (CI, 58% to 73%) allocated to sulfonylurea required additional therapy with metformin or insulin to control symptoms and maintain fasting plasma glucose levels less than 15 mmol/L. Patients allocated to insulin gained more weight and had more hypoglycemic attacks than did patients allocated to sulfonylurea. Obese patients allocated to metformin gained the least weight and had the fewest hypoglycemic attacks. For all therapies, control achieved at 6 years was worse in the primary diet failure group than in the diet-controlled group.Conclusions:Because initial insulin therapy induced more hypoglycemic reactions and weight gain without necessarily providing better control, it may be reasonable to start with oral agents and change to insulin if goals for glycemic levels are not achieved.References1. Guidelines for good practice in the diagnosis and treatment of non–insulin-dependent diabetes mellitus. Report of a joint working party of the British Diabetic Association, the Research Unit of the Royal College of Physicians, and the Royal College of General Practitioners. J R Coll Physicians Lond. 1993; 27:259-66. Google Scholar2. Consensus statement. The pharmacological treatment of hyperglycemia in NIDDM. Diabetes Care. 1996; 19(Suppl 1):S54-61 Google Scholar3. UK Prospective Diabetes Study (UKPS). VIII. Study design, progress and performance. Diabetologia. 1991; 34:877-90. Google Scholar4. 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Google Scholar Author, Article, and Disclosure InformationAffiliations: Acknowledgments: The authors thank the patients and the National Health Serviceand non-National Health Service staff at the centers for their cooperation.Grant Support: By grants from the United Kingdom Medical Research Council; the British Diabetic Association; the United Kingdom Department of Health; The National Eye Institute (5 U10 EY07049-11) and The National Institute of Diabetes and Digestive and Kidney Diseases (2 R01 DK33152-07), National Institutes of Health; The British Heart Foundation; The Health Promotion Research Trust; The Clothworkers' Foundation; Charles Wolfson Charitable Trust; The Alan and Babette Sainsbury Trust; and The Oxford University Medical Research Fund Committee.Corresponding Author: United Kingdom Prospective Diabetes Study Group, Diabetes Research Laboratories, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United Kingdom.Current Author Addresses: Drs. Wright, Cull, Holman, and Turner: United Kingdom Prospective Diabetes Study Group, Diabetes Research Laboratories, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United Kingdom. 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DeFronzo, MDEffects of Metformin in Patients with Poorly Controlled, Insulin-Treated Type 2 Diabetes Mellitus A Randomized, Double-Blind, Placebo-Controlled TrialLarissa Avilés-Santa, MD, Joyce Sinding, MSN, RN, and Philip Raskin, MDDiabetische NephropathieGlucose control guidelines: current conceptsEffect of high-carbohydrate versus high-monounsaturatedfatty acid diet on metabolic control in diabetes and hyperglycemic patientsTherapie des Diabetes mellitusHypoglycemia in Type 2 Diabetes 1 February 1998Volume 128, Issue 3Page: 165-175KeywordsAttentionBlood plasmaDietGlucoseHemoglobinHyperglycemiaHypoglycemicsInsulinOverweightType 2 diabetes ePublished: 15 August 2000 Issue Published: 1 February 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...