Online citations, reference lists, and bibliographies.
← Back to Search

Intensive Blood-glucose Control With Sulphonylureas Or Insulin Compared With Conventional Treatment And Risk Of Complications In Patients With Type 2 Diabetes (UKPDS 33)

UK Prospective Diabetes Study Group
Published 1998 · Medicine
Referenced 1 time by Citationsy Users

Cite This
Download PDF
Analyze on Scholarcy
Share
BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial. METHODS 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy. FINDINGS Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg). INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)
This paper references
10.1007/s001250050626
NIDDM: a rapid progressive disease Results from a long-term, randomised, comparative study of insulin or sulphonylurea treatment
K. Birkeland (1996)
10.1007/s001250051438
Cardiovascular effects of sulphonylurea derivatives
P. Smits (1997)
Hypertension secondary to chlorpropamide with amelioration by changing to insulin.
J. Schmitt (1993)
10.1016/0021-9681(79)90051-1
Hyperglycaemia and coronary heart disease: the Whitehall study.
J. Fuller (1979)
10.1007/BF00418542
Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients
S. Kumar (2004)
10.2337/diacare.2.2.131
Relationship of Glucose Tolerance and Plasma Insulin to the Incidence of Coronary Heart Disease: Results from Two Population Studies in Finland
K. Pyörälä (1979)
10.2337/diacare.13.6.631
Insulin and Atheroma: 20-Yr Perspective
R. Stout (1990)
10.1111/j.1464-5491.1994.tb02032.x
UK Prospective Diabetes Study (UKPDS) XI: Biochemical Risk Factors in Type 2 Diabetic Patients at Diagnosis Compared with Age‐matched Normal Subjects
S. E. Manley (1994)
The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus
Jean-Louis Chiasson (1994)
A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results.
C. Meinert (1970)
10.2337/diacare.18.8.1113
Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM): Results of the feasibility trial
C. Abraira (1995)
10.2337/diacare.21.1.S23
Standards of Medical Care for Patients With Diabetes Mellitus
(1998)
10.1056/NEJM199309303291401
The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long‐Term Complications in Insulin‐Dependent Diabetes Mellitus
D. Nathan (1993)
Sulphonylureas in the treatment of non-insulin-dependent diabetes.
A. Melander (1988)
UK Prospective Diabetes Study 17 : A nine - year update of a randomized , controlled trial on the effect of improved metabolic control on complications in non - insulin - dependent diabetes mellitus
J Fuller (1996)
10.2337/diacare.16.1.21
Intensive Conventional Insulin Therapy for Type II Diabetes: Metabolic effects during a 6-mo outpatient trial
R. Henry (1993)
10.7326/0003-4819-124-1_Part_2-199601011-00005
Exogenous Insulin Administration and Cardiovascular Risk in Non-Insulin-dependent and Insulin-dependent Diabetes Mellitus
S. Genuth (1996)
10.1016/S0140-6736(69)90097-X
Insulin and atherosclerosis.
R. W. Stout (1969)
10.1016/0168-8227(95)01103-K
Potassium channels in the cardiovascular system.
G. Pogátsa (1995)
10.1038/eye.1989.119
Long term effectiveness of photocoagulation for diabetic maculopathy
E. Davies (1989)
Therapeutic requirements to maintain tight blood pressure control
RR Holman (1996)
10.1001/JAMA.1997.03550200039029
Starting insulin therapy in patients with type 2 diabetes: effectiveness, complications, and resource utilization.
R. Hayward (1997)
10.2337/diacare.18.3.307
Comparison of Insulin With or Without Continuation of Oral Hypoglycemic Agents in the Treatment of Secondary Failure in NIDDM Patients
C. Chow (1995)
10.1111/j.1365-2796.1991.tb00415.x
Intensified conventional insulin treatment retards the microvascular complications of insulin‐dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years
P. Reichard (1991)
10.1097/00019616-199303000-00016
Comparison of Insulin Regimens in Patients with Non-Insulin Dependent Diabetes Mellitus
H. Yki-Jaarvinen (1993)
10.1056/NEJM199604113341504
Hyperinsulinemia as an independent risk factor for ischemic heart disease.
J. Després (1996)



This paper is referenced by
10.2147/IJGM.S119965
Multi-ethnic differences in HbA1c, blood pressure, and low-density-lipid cholesterol control among South Africans living with type 2 diabetes, after a 4-year follow-up
Y. Pinchevsky (2016)
The role of coping with disease in adherence to treatment regimen and disease control in type 1 and insulin treated type 2 diabetes mellitus.
B. Turan (2002)
10.1001/archinte.168.21.2355
A randomized trial of the effect of community pharmacist and nurse care on improving blood pressure management in patients with diabetes mellitus: study of cardiovascular risk intervention by pharmacists-hypertension (SCRIP-HTN).
Donna L. McLean (2008)
10.1002/msj.20117
Glycemic targets for patients with type 2 diabetes mellitus.
Ole-Petter R Hamnvik (2009)
10.2337/dc05-2232
Diabetes and Driving
A. D. M. Stork (2006)
10.2337/DIACARE.28.12.2948
Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities.
N. Zammitt (2005)
10.1186/1743-7075-3-22
Low-carbohydrate diet in type 2 diabetes. Stable improvement of bodyweight and glycemic control during 22 months follow-up
J. V. Nielsen (2006)
10.1089/DIA.2006.8.347
Improving the quality of self-monitoring blood glucose measurement: a study in reducing calibration errors.
John M Baum (2006)
10.1111/cei.12020
Differential effect of hyperglycaemia on the immune response in an experimental model of diabetes in BALB/cByJ and C57Bl/6J mice: participation of oxidative stress
M. Rubinstein (2013)
10.1185/03007995.2010.494451
Economic models in type 2 diabetes
Y. Yi (2010)
10.1046/j.1365-2362.2002.00965.x
Blood glucose pre‐prandial baseline decreases from morning to evening in type 2 diabetes: role of fasting blood glucose and influence on post‐prandial excursions
M. Trovati (2002)
10.1161/HYPERTENSIONAHA.108.128413
Blood Pressure Is a Major Risk Factor for Renal Death: An Analysis of 560 352 Participants From the Asia-Pacific Region
C. O’Seaghdha (2009)
10.1159/000488826
Angiopoietin-2, Renal Deterioration, Major Adverse Cardiovascular Events and All-Cause Mortality in Patients with Diabetic Nephropathy
Y. Tsai (2018)
10.1046/j.1463-1326.2002.00202.x
DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction): theory and practice
M. Davies (2002)
10.1046/j.1463-1326.2003.00297.x
Greater reductions in A1C in type 2 diabetic patients new to therapy with glyburide/metformin tablets as compared to glyburide co‐administered with metformin
L. Blonde (2003)
10.1111/j.1464-5491.2008.02565.x
International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations
A. Ceriello (2008)
10.1177/0091270010368281
Database Evaluation of the Effects of Long‐Term Rosiglitazone Treatment on Cardiovascular Outcomes in Patients With Type 2 Diabetes
R. Loebstein (2011)
10.4061/2011/567389
Metabolic Syndrome and Renal Injury
Yi-Jing Sheen (2011)
10.1111/j.1365-2796.2010.02265.x
New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR)
K. Eeg-Olofsson (2010)
10.1002/dmrr.613
Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction
L. Piconi (2006)
10.1111/j.1742-1241.2007.01309.x
Why, when and how to initiate insulin therapy in patients with type 2 diabetes
J. Tibaldi (2007)
10.1124/jpet.106.110296
Sergliflozin, a Novel Selective Inhibitor of Low-Affinity Sodium Glucose Cotransporter (SGLT2), Validates the Critical Role of SGLT2 in Renal Glucose Reabsorption and Modulates Plasma Glucose Level
K. Katsuno (2007)
10.2337/dc10-zb11
Cardiovascular Disease and Glycemic Treatment
Z. Bloomgarden (2010)
10.1111/j.1742-1241.2007.01360.x
The importance of β‐cell management in type 2 diabetes
E. Standl (2007)
10.1111/j.1742-1241.2010.02589.x
Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase‐4 inhibitor, and pioglitazone on glycemic control and measures of β‐cell function in patients with type 2 diabetes
K. Yoon (2011)
10.3810/pgm.2002.09.1322
Peripheral artery disease
C. Solomon (2002)
10.1111/j.1445-5994.2008.01638.x
Glucose control peri‐myocardial infarction
G. Braatvedt (2008)
10.1111/j.1365-2710.2006.00705.x
Trends in the use of oral antidiabetic drugs by outpatients in Taiwan: 1997–2003
C.-W. Chiang (2006)
10.1111/j.1529-8027.2009.00237.x
Hyperlipidemia: a new therapeutic target for diabetic neuropathy
A. M. Vincent (2009)
10.1186/s12902-019-0364-5
A Greek registry of current type 2 diabetes management, aiming to determine core clinical approaches, patterns and strategies
S. Liatis (2019)
10.1530/EJE-15-1149
Time to insulin initiation and long-term effects of initiating insulin in people with type 2 diabetes mellitus: the Hoorn Diabetes Care System Cohort Study.
R. Mast (2016)
10.2337/ds17-0082
Achievement of Target A1C <7.0% (<53 mmol/mol) by U.S. Type 2 Diabetes Patients Treated With Basal Insulin in Both Randomized Controlled Trials and Clinical Practice
Lawrence Blonde (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar