UKPDS

Abstract: Aim To review the world-wide impact of the United Kingdom Prospective Diabetes Study (UKPDS) on diabetes health care since publication of the main study results in 1998. Methods The major papers published by the UKPDS were reviewed, e-mails and faxes were sent to diabetes associations in various regions of the world seeking information on trends in HbA1c over the past decade and similar information was obtained from a major USA laboratory. Results The UKPDS extended to type 2 diabetes and brought to completion the case for linking the microvascular vascular complications of diabetes to control of blood glucose initially demonstrated by the Diabetes Control and Complications Trial (DCCT). This helped set the standard of care for diabetes to seek an HbA1c goal of at least < 7.0% with intensive glycemic treatment and formed a fundamental part of continuing medical education. This also helped stimulate new hypoglycemic drug development and the preferential use of metformin as first line therapy was supported by UKPDS results. In many areas of the world, including the United Kingdom and the USA, a national trend to lower HbA1c levels has been seen. Economic analyses have shown UKPDS intensive treatment to be cost-effective at 6028 Ibs. per quality life year gained, imposing a reasonable burden on the British National health care budget. Conclusions The UKPDS was a landmark study in the treatment of type 2 diabetes from the time of diagnosis that has influenced standards of care and treatment guidelines throughout the world.

 UKPDS;  

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Abstract: AIMS/HYPOTHESIS: This study estimated the economic efficiency (1) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension, and (2) of metformin therapy in type 2 diabetic patients who were overweight. METHODS: We conducted cost-utility analysis based on patient-level data from a randomised clinical controlled trial involving 4,209 patients with newly diagnosed type 2 diabetes conducted in 23 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study (UKPDS). Three different policies were evaluated: intensive blood glucose control with sulphonylurea/insulin; intensive blood glucose control with metformin for overweight patients; and tight blood pressure control of hypertensive patients. Incremental cost : effectiveness ratios were calculated based on the net cost of healthcare resources associated with these policies and on effectiveness in terms of quality-adjusted life years gained, estimated over a lifetime from within-trial effects using the UKPDS Outcomes Model. RESULTS: The incremental cost per quality-adjusted life years gained (in year 2004 UK prices) for intensive blood glucose control was 6,028 UK pounds, and for blood pressure control was 369 UK pounds. Metformin therapy was cost-saving and increased quality-adjusted life expectancy. CONCLUSIONS/INTERPRETATION: Each of the three policies evaluated has a lower cost per quality-adjusted life year gained than that of many other accepted uses of healthcare resources. The results provide an economic rationale for ensuring that care of patients with type 2 diabetes corresponds at least to the levels of these interventions.

 prevention;  diabetes;  nephropathy;  glycemic control;  Insulin;  economic evaluation;  metformin;  UKPDS;  

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Abstract: AIMS/HYPOTHESIS: The aim of this study was to develop a simulation model for type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime, in order to calculate health economic outcomes such as quality-adjusted life expectancy. METHODS: Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospective Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes Model was used to simulate the mean difference in expected quality-adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control. RESULTS: The models forecasts fell within the 95% confidence interval for the occurrence of observed events during the UKPDS follow-up period. When the model was used to simulate event history over patients lifetimes, those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality-adjusted life years, and those receiving treatment with intensive glucose control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95% CI: -0.48 to 1.03). CONCLUSIONS/INTERPRETATIONS: The UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients lifetimes. Its validity in estimating outcomes in other groups of patients, however, remains to be evaluated. The model allows simulation of a range of long-term outcomes, which should assist in informing future economic evaluations of interventions in type 2 diabetes.

 diabetes;  economic evaluation;  UKPDS;  

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Abstract: BACKGROUND: The progression of nephropathy from diagnosis of type 2 diabetes has not been well described from a single population. This study sought to describe the development and progression through the stages of microalbuminuria, macroalbuminuria, persistently elevated plasma creatinine or renal replacement therapy (RRT), and death. METHODS: Using observed and modeled data from 5097 subjects in the UK Prospective Diabetes Study, we measured the annual probability of transition from stage to stage (incidence), prevalence, cumulative incidence, ten-year survival, median duration per stage, and risk of death from all-causes or cardiovascular disease. RESULTS: From diagnosis of diabetes, progression to microalbuminuria occurred at 2.0% per year, from microalbuminuria to macroalbuminuria at 2.8% per year, and from macroalbuminuria to elevated plasma creatinine (>or=175 micromol/L) or renal replacement therapy at 2.3% per year. Ten years following diagnosis of diabetes, the prevalence of microalbuminuria was 24.9%, of macroalbuminuria was 5.3%, and of elevated plasma creatinine or RRT was 0.8%. Patients with elevated plasma creatinine or RRT had an annual death rate of 19.2% (95% confidence interval, CI, 14.0 to 24.4%). There was a trend for increasing risk of cardiovascular death with increasing nephropathy (P < 0.0001), with an annual rate of 0.7% for subjects in the stage of no nephropathy, 2.0% for those with microalbuminuria, 3.5% for those with macroalbuminuria, and 12.1% with elevated plasma creatinine or RRT. Individuals with macroalbuminuria were more likely to die in any year than to develop renal failure. CONCLUSIONS: The proportion of patients with type 2 diabetes who develop microalbuminuria is substantial with one quarter affected by 10 years from diagnosis. Relatively fewer patients develop macroalbuminuria, but in those who do, the death rate exceeds the rate of progression to worse nephropathy.

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Abstract: OBJECTIVE: To estimate the incremental cost of implementing policies for intensive control of blood glucose concentration and blood pressure for all patients with type 2 diabetes in England. DESIGN: Extrapolation of resource use and cost data derived from a randomised controlled trial. SETTING: General practice, outpatient care, and inpatient care. POPULATION: Trial population with diagnosed type 2 diabetes in England extrapolated to the population of England. MAIN OUTCOME MEASURES: Total costs based on use of healthcare resources including costs of management, treatment, and hospitalisation. RESULTS: The incremental net annual cost of implementing intensive control of blood glucose and blood pressure to all people with diagnosed type 2 diabetes in England is estimated to be pound 100.5m (\$156m; euro;159m), which is equivalent to less than 1\% of the proposed additional annual expenditure on the NHS in 2001-5. This estimate varied in sensitivity analyses from pound 67m to pound 121m. CONCLUSIONS: Policies to improve control of blood glucose and blood pressure of people with type 2 diabetes are effective in reducing complications associated with the disease and are also cost effective. The total cost represents a small fraction of the NHSs spending plans.

 prevention;  diabetes;  nephropathy;  glycemic control;  economic evaluation;  UKPDS;  

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Abstract: CONTEXT: Several treatment interventions can reduce complications of type 2 diabetes, but their relative cost-effectiveness is not known. OBJECTIVE: To estimate the incremental cost-effectiveness of intensive glycemic control (relative to conventional control), intensified hypertension control, and reduction in serum cholesterol level for patients with type 2 diabetes. DESIGN, SETTING, AND PATIENTS: Cost-effectiveness analysis of a hypothetical cohort of individuals living in the United States, aged 25 years or older, who were newly diagnosed as having type 2 diabetes. The results of the United Kingdom Prospective Diabetes Study (UKPDS) and other studies were used to create a model of disease progression and treatment patterns. Costs were based on those used in community practices in the United States. INTERVENTIONS: Insulin or sulfonylurea therapy for intensive glycemic control; angiotensin-converting enzyme inhibitor or beta-blocker for intensified hypertension control; and pravastatin for reduction of serum cholesterol level. MAIN OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) gained. Costs (in 1997 US dollars) and QALYs were discounted at a 3% annual rate. RESULTS: The incremental cost-effectiveness ratio for intensive glycemic control is $41384 per QALY; this ratio increased with age at diagnosis from $9614 per QALY for patients aged 25 to 34 years to $2.1 million for patients aged 85 to 94 years. For intensified hypertension control the cost-effectiveness ratio is -$1959 per QALY. The cost-effectiveness ratio for reduction in serum cholesterol level is $51 889 per QALY; this ratio varied by age at diagnosis and is lowest for patients diagnosed between the ages of 45 and 84 years. CONCLUSIONS: Intensified hypertension control reduces costs and improves health outcomes relative to moderate hypertension control. Intensive glycemic control and reduction in serum cholesterol level increase costs and improve health outcomes. The cost-effectiveness ratios for these 2 interventions are comparable with those of several other frequently adopted health care interventions.

 diabetes;  cdc;  glycemic control;  Insulin;  Cholesterol;  UKPDS;  

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Abstract: AIMS: To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. DESIGN: A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. SETTING: Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. SUBJECTS: Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. MAIN OUTCOME MEASURES: Life expectancy and mean cost per patient. RESULTS: There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95\% confidence interval 188 UK pounds, 1682 UK pounds). This 14\% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. CONCLUSIONS: Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)

 prevention;  diabetes;  nephropathy;  economic evaluation;  blood pressure control;  UKPDS;  

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Abstract: OBJECTIVE: To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes. DESIGN: Incremental cost effectiveness analysis alongside randomised controlled trial. SETTING: 23 UK hospital clinic based study centres. PARTICIPANTS: 3867 patients with newly diagnosed type 2 diabetes (mean age 53 years). INTERVENTIONS: Conventional (primarily diet) glucose control policy versus intensive control policy with a sulphonylurea or insulin. Main outcome measures: Incremental cost per event-free year gained within the trial period. RESULTS: Intensive glucose control increased trial treatment costs by pound 695 (95\% confidence interval pound 555 to pound 836) per patient but reduced the cost of complications by pound 957 (pound 233 to pound 1681) compared with conventional management. If standard practice visit patterns were assumed rather than trial conditions, the incremental cost of intensive management was pound 478 (-pound 275 to pound 1232) per patient. The within trial event-free time gained in the intensive group was 0.60 (0.12 to 1.10) years and the lifetime gain 1.14 (0.69 to 1.61) years. The incremental cost per event-free year gained was pound 1166 (costs and effects discounted at 6\% a year) and pound 563 (costs discounted at 6\% a year and effects not discounted). CONCLUSIONS: Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications.

 prevention;  diabetes;  nephropathy;  glycemic control;  Insulin;  economic evaluation;  UKPDS;  

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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)

 diabetes;  glycemic control;  Insulin;  clinical trial;  UKPDS;  

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Abstract: OBJECTIVE: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. DESIGN: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a beta blocker atenolol as main treatment) with less tight control aiming at a blood pressure of <180/105 mm Hg. SETTING: 20 hospital based clinics in England, Scotland, and Northern Ireland. SUBJECTS: 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years. MAIN OUTCOME MEASURES: Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography. RESULTS: Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%) (P=0.013), and 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) and a 47% reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures. CONCLUSION: Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.

 diabetes;  blood pressure control;  clinical trial;  UKPDS;  

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Abstract: OBJECTIVE: To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. DESIGN: Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of =300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). CONCLUSION: Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.

 diabetes;  Captopril;  Atenolol;  UKPDS;  

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Abstract: OBJECTIVES: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. DESIGN: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. SETTING: 20 hospital based clinics in England, Scotland, and Northern Ireland. SUBJECTS: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). MAIN OUTCOME MEASURE: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. RESULTS: Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to pound1049 (costs and effects discounted at 6% per year) and pound434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was pound720 (costs and effects discounted at 6% per year) and pound291 (costs discounted at 6% per year and effects not discounted). CONCLUSIONS: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

 economic evaluation;  blood pressure control;  UKPDS;  

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Abstract: The UK Prospective Diabetes Study (UKPDS) is a multi-centre, prospective, randomised, intervention trial of 5100 newly-diagnosed patients with Type 2 (non-insulin-dependent) diabetes mellitus which aims to determine whether improved blood glucose control will prevent complications and reduce the associated morbidity and mortality. Newly presenting Type 2 diabetic patients aged 25-65 years inclusive, median age 53 years, median body mass index 28 kg/m2 and median fasting plasma glucose 11.3 mmol/l, were recruited and treated initially by diet. Ninety five percent remained hyperglycaemic (fasting plasma glucose greater than 6 mmol/l) and were randomly allocated to different therapies. In the main randomisation, those who were asymptomatic and had fasting plasma glucose under 15 mmol/l were allocated either to diet policy, or to active policy with either insulin or sulphonylurea aiming to reduce the fasting plasma glucose to under 6 mmol/l. Over 3 years, the median fasting plasma glucose in those allocated to diet policy was 8.9 mmol/l compared with 7.0 mmol/l in those allocated to active policy. The Hypertension in Diabetes Study has been included in a factorial design to assess whether improved blood pressure control will be advantageous. Patients with blood pressure greater than or equal to 160/90 mm Hg were randomly allocated to tight control aiming for less than 150/85 mm Hg with either an angiotensin-converting enzyme inhibitor or a Beta-blocker or to less tight control aiming for less than 200/105 mm Hg. The endpoints of the studies are major clinical events which affect the life and well-being of patients, such as heart attacks, angina, strokes, amputations, blindness and renal failure. To date, 728 patients have had at least one clinical endpoint. Surrogate endpoints include indices of macrovascular and microvascular disease detected by ECG with Minnesota Coding, retinal colour photography and microalbuminuria. The studies also aim to evaluate potential risk factors for the development of diabetic complications such as smoking, obesity, central adiposity, plasma LDL- and HDL-cholesterol, triglyceride, insulin, urate and other biochemical variables. The studies are planned to terminate in 1994, with a median follow-up of 9 years (range 3-16 years) for the glucose study and 5 years (range 2-6 years) for the hypertension study.

 UKPDS;  

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