A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study

Abstract

BackgroundIntensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain.ObjectiveTo quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes.DesignPragmatic, multicentre, cluster-randomised, parallel-group trial.SettingThree hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK.ParticipantsIndividuals aged 40–69 years with screen-detected diabetes.InterventionsScreening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol.Main outcome measuresThe primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3;©Isis Innovation Ltd 2010; seewww.dtu.ox.ac.uk/outcomesmodel(accessed 27 January 2016)].ResultsWe included 3055 (RC,n = 1377; IT,n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient.ConclusionsCompared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted.Trial registrationClinicalTrials.gov NCT00237549.Funding detailsThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.

Evaluation of the Diabetes Screening Component of a National Cardiovascular Risk Assessment Programme in England: a Retrospective Cohort Study

“…Similarly, individuals at high risk of T2D, and patients with newly detected NDH and T2D registered with high coverage practices had lower fasting plasma glucose levels than those registered with low coverage practices. This finding is also in line with previous studies reporting lower blood glucose levels among individuals with screen-detected T2D compared with patients detected in routine clinical care 28 .…”

Treat‐to‐target HbA1c and lipid profile to prolong β‐cell mass/function and optimize treatment goal attainment

“…On the other hand, the intensive multifactorial approach to treat these people has been shown to be an efficient and cost‐effective way to prevent development and progression of these complications . However, in our country, only about 4% of the population attains this multifactorial goal.…”

Care of type II diabetes in older adults: untapped opportunities and remaining challenges

“…Counseling on nutrition, exercise, smoking cessation, blood pressure control, eye examination, foot, and dental examination are essential periodic routine care. Vaccinations against pneumococcus, influenza, and hepatitis represent some preventive measures [10]. Laboratory monitoring includes periodic fasting lipid profile, HbA 1c , urine albumin-to-creatinine ratio, and serum creatinine.…”

“…Laboratory monitoring includes periodic fasting lipid profile, HbA 1c , urine albumin-to-creatinine ratio, and serum creatinine. The appropriate target for HbA 1c can also be individualized based on overall health and life expectancy, and identified patient-specific risks for hypoglycemia and the ability of the patient to adopt and adhere to specific treatment regimens [3][4][5][6][7][8]10]. Because overtreatment can result in hypoglycemia, the avoidance of hypoglycemia is an important consideration in establishing goals and choosing therapeutic agents in older adults.…”

“…Therefore, proper adherence to medication and injection practices among patients with diabetes cannot be overemphasized to result in optimal health and quality of life [10]. Treatment must be individualized.…”