Open Access
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
- Vol. 352, Iss: 9131, pp 837-853
Reads0
Chats0
TLDR
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 were compared.Abstract:
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)read more
Citations
More filters
Journal ArticleDOI
Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting.
Shoko Maru,Gary G. Koch,Monika Stender,Douglas Clark,Laura Gibowski,H. Petri,Alice D. White,Ross J. Simpson +7 more
TL;DR: The use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure, but this risk does not persist beyond the first year after diagnosis of diabetes and does not appear to differ among the types of drug therapy examined.
Journal ArticleDOI
Recent findings concerning thiazolidinediones in the treatment of diabetes.
Guenther Boden,Meijuan Zhang +1 more
TL;DR: Because PPar-α and -γ agonists improve atherosclerotic vascular disease and insulin sensitivity, respectively, dual PPAR-α/γ agonist may be useful in treating patients with the metabolic syndrome.
Journal ArticleDOI
Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care
TL;DR: Lower risks of hyperglycaemia are found among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with met formin alone, which could have implications for the prescribing of hypoglycaemic drugs.
Journal ArticleDOI
Glycated hemoglobin as a marker of cardiovascular risk.
Kay-Tee Khaw,Nicholas J. Wareham +1 more
TL;DR: Glycated hemoglobin concentration predicts cardiovascular risk both in people with diabetes and in the general population, and may help identify individuals at higher risk of cardiovascular disease for targeted interventions, including blood pressure or cholesterol reduction.
Journal ArticleDOI
Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model
Tsuguhito Ota,Toshinari Takamura,Hitoshi Ando,Erika Nohara,Haruhisa Yamashita,Kenichi Kobayashi +5 more
TL;DR: In this hypertensive model of diabetic nephropathy, cerivastatin decreased albuminuria through suppression of glomerular hyperfiltration, mesangial expansion, and the loss of charge barrier independently of a cholesterol-lowering effect.
References
More filters
Journal Article
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
R C Turner,Rury R. Holman,Carole A. Cull,Irene M Stratton,David R Matthews,V Frighi,Susan E. Manley,Andrew Neil,K McElroy,D Wright,E. M. Kohner,Caroline S. Fox,D R Hadden,Z Mehta,Albert V. Smith,Z Nugent,Richard Peto,A I Adlel,Jim Mann,P A Bassett,S. Oakes,Tim Dornan,Stephen J Aldington,H Lipinski,R Collum,K Harrison,C MacIntyre,S Skinner,A Mortemore,D Nelson,S Cockley,S Levien,L Bodsworth,R Willox,T Biggs,S Dove,E Beattie,M Gradwell,S Staples,R Lam,F Taylor,L Leung,R D Carter,S M Brownlee,K E Fisher,K Islam,R. Jelfs,P A Williams,F A Williams,P J Sutton,A Ayres,Lisa Logie,C Lovatt,M A Evans,L A Stowell,I Ross,I A Kennedy,D. J. Croft,A H Keen,C Rose,M Raikou,A E Fletcher,Christopher J. Bulpitt,Clare Battersby,J S Yudkin,Richard Stevens,M R Stearn,S L Palmer,M S Hammersley,S L Franklin,R S Spivey,Jonathan C. Levy,C R Tidy,N J Bell,J Steemson,B A Barrow,R Coster,K Waring,L Nolan,E Truscott,N Walravens,L Cook,H Lampard,C Merle,P Parker,J McVittie,I Draisey,L E Murchison,Brunt Ahe.,M J Williams,D W Pearson,Petrie Xmp.,Lean Mej.,D Walmsley,F Lyall,E Christie,J Church,E Thomson,A Farrow,J M Stowers,M Stowers,K McHardy,N Patterson,Alex D. Wright,N A Levi,Shearer Aci.,Thompson Rjw.,G Taylor,S Rayton,M Bradbury,A Glover,A Smyth-Osbourne,C Parkes,J Graham,P England,S Gyde,C Eagle,B Chakrabarti,Josh Smith,J Sherwell,N. W. Oakley,M. Whitehead,G P Hollier,T. Pilkington,J Simpson,Michael W. Anderson,S Martin,J Kean,B Rice,A Rolland,J Nisbet,E M Kohner,A Dornhorst,M C Doddridge,M Dumskyij,S Walji,P Sharp,M Sleightholm,G Vanterpool,G Frost,M Roseblade,S Elliott,S Forrester,Meredith C. Foster,K Myers,R Chapman,J R Hayes,R W Henry,M S Featherston,Archbold Gpr.,M Copeland,R Harper,I Richardson,H A Davison,L Alexander,Scarpello Jhb.,D E Shiers,R J Tucker,Worthington Jrh.,S Angris,A Bates,J Walton,M Teasdale,J Browne,S Stanley,B A Davis,R C Strange,Hadden,L Kennedy,A B Atkinson,P M Bell,D R McCance,J Rutherford,A M Culbert,C Hegan,H Tennet,N Webb,I Robinson,J Holmes,S Nesbitt,A S Spathis,S Hyer,M E Nanson,L M James,J M Tyrell,C Davis,P Strugnell,M Booth,H Petrie,D Clark,S Hulland,J L Barron,B C Gould,J Singer,A Badenoch,M McGregor,L Isenberg,M Eckert,K Alibhai,E Marriot,Christopher E. Cox,R Price,M Fernandez,A Ryle,S Clarke,G Wallace,E Mehmed,J A Lankester,E Howard,A Waite,S MacFarlane,R H Greenwood,J Wilson,M J Denholm,R C Temple,K Whitfield,F Johnson,C Munroe,S Gorick,E Duckworth,M Fatman,S Rainbow,L J Borthwick,D J Wheatcroft,R J Seaman,R A Christie,W Wheatcroft,P Musk,Jennifer White,S McDougal,M Bond,P Raniga,J L Day,M J Doshi,James G. Wilson,J. Howard-Williams,H Humphreys,A Graham,K Hicks,S Hexman,P Bayliss,D Pledger,R W Newton,R T Jung,C Roxburgh,B Kilgallon,L Dick,N Waugh,S Kilby,A Ellingford,J Burns,C Fox,M C Holloway,H M Coghill,N Hein,A J Fox,W Cowan,M Richard,K Quested,S J Evans,Richard B Paisey,Brown Npr.,A J Tucker,R Paisey,F Garrett,J Hogg,P Park,K Williams,P Harvey,R Wilcocks,S Mason,J. C. Frost,C Warren,P Rocket,L Bower,J M Roland,D J Brown,J Youens,K Stanton-King,H Mungall,V Ball,W Maddison,D Donnelly,S King,P Griffin,Sidney C. Smith,S Church,Graham Dunn,Andrew D. Wilson,K Palmer,P M Brown,D Humphriss,Davidson Ajm.,Richard Rose,L Armistead,S Townsend,P Poon,Peacock Ida.,Culverwell Njc.,M H Charlton,Connolly Bps.,J Peacock,J Barrett,J Wain,W Beeston,George L. King,P G Hill,Boulton Ajm.,A M Robertson,V Katoulis,A Olukoga,H McDonald,S Kumar,F Abouaesha,B Abuaisha,E A Knowles,S Higgins,J Booker,J Sunter,K Breislin,R Parker,P Raval,J Curwell,H Davenport,G Shawcross,A Prest,J Grey,H Cole,C Sereviratne,R J Young,J R Clyne,M Gibson,I O'Connell,L M Wong,S J Wilson,K L Wright,Chris Wallace,D McDowell,A C Burden,E M Sellen,R Gregory,M Roshan,N Vaghela,M Burden,C Sherriff,S Mansingh,J Clarke,J Grenfell,Je Tooke,K. M. MacLeod,C Seamark,M Rammell,C Pym,J Stockman,C Yeo,J Piper,L Leighton,Ellen Green,M Hoyle,K Jones,A Hudson,A J James,Angela C. Shore,A Higham,B Martin,Neil Haw.,Butterfield Wjh.,Doll Wrs.,R Eastman,F R Ferris,N Kurinij,K McPherson,R F Mahler,Tom W. Meade,G Shafer,P J Watkins,H Keen,D Siegel,D J Betteridge,R D Cohen,D Currie,Julie L Darbyshire,J V Forrester,T Guppy,D G Johnston,Alistair McGuire,Mike Murphy,A M el-Nahas,B Pentecost,D Spiegelhalter,Alberti Kgmm.,R Denton,Philip Home,S Howell,Jarrett,V Marks,Michael Marmot,J D Ward,Grp Ukpds. +398 more
TL;DR: In this article, 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 were compared.
Journal ArticleDOI
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
Irene M Stratton,Amanda I Adler,H. Andrew W. Neil,David R. Matthews,Susan E. Manley,Carole A. Cull,D R Hadden,Robert C Turner,Rury R. Holman +8 more
TL;DR: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia, with the lowest risk being in those with HbA1c values in the normal range (<6.0%).
Journal ArticleDOI
Hyperinsulinemia as an Independent Risk Factor for Ischemic Heart Disease
Jean-Pierre Després,Benoît Lamarche,Pascale Mauriège,Bernard Cantin,Gilles R. Dagenais,Sital Moorjani,Paul-J. Lupien +6 more
TL;DR: High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men after adjustment for other risk factors.
Journal Article
A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results.
Journal ArticleDOI
UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes
Robert C. Turner,Irene M Stratton,V A Horton,Sue Manley,Paul Zimmet,Ian R Mackay,M Shattock,Gian Franco Bottazzo,Rury R. Holman +8 more
TL;DR: In this article, the presence of either or both antibodies characterises a subtype of diabetes and provides better prediction of requirement for insulin therapy by 6 years' follow-up than clinical variables.
Related Papers (5)
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
Anushka Patel,Stephen MacMahon,John Chalmers,Bruce Neal,Laurent Billot,Mark Woodward,Mark Woodward,Michel Marre,Mark E. Cooper,Paul Glasziou,Paul Glasziou,Diederick E. Grobbee,Pavel Hamet,Stephen B. Harrap,Simon Heller,Lisheng Liu,Giuseppe Mancia,Carl Erik Mogensen,C. Y. Pan,Neil R Poulter,Anthony Rodgers,Bryan Williams,Severine Bompoint,Bastiaan E. de Galan,Bastiaan E. de Galan,Rohina Joshi,F. Travert +26 more