The ADDITION-Europe study

1. The ADDITION-Europe study Denmark UK Netherlands Simon Griffin, Knut Borch-Johnsen, Melanie Davies, Kamlesh Khunti, Guy Rutten, Annelli Sandbæk, Stephen Sharp, Rebecca Simmons, Maureen van den Donk, Nicholas Wareham, Torsten Lauritzen www.addition.au.dk

2. Background Type 2 diabetes is common, costly and associated with a significant burden of morbidity and mortality Single risk factor interventions can reduce risk of complications Intensive multifactorial treatment can halve the risk of CVD in people with longstanding diabetes The effectiveness of multifactorial treatment in people with screen detected diabetes is unknown

3. Diabetes detectable biochemically Diabetes detectable clinically Background Diabetes detected by screening 0 years ~4 years ~8 years If we find and treat people earlier, can we reduce the chance of them dying early and/or suffering from heart attacks and strokes?

4. Background The ADDITION-Europe study involves individuals at an earlier stage, i.e. screen detected diabetes is set in daily clinical practice in primary care assesses effectiveness of multifactorial treatment is randomised at the general practice level is pragmatic in design

5. Five-year data collection 156 practices provided routine care 161 practices provided intensive treatment Participants: 1,379 Participants: 1,678 Follow-up 1,377 (99.9%) with endpoint data 92 (6.7%) died Of those alive 1,048 (81%) measured at CRF 1,241 (96%) laboratory data collected Follow-up 1,678 (100%) with endpoint data 104 (6.2%) died Of those alive 1,352 (86%) measured at CRF 1,532 (97%) laboratory data collected

6. Routine care Intensive treatment BP-lowering Statins Glucose-lowering Baseline Baseline Baseline Baseline Baseline Baseline Prescribed treatmentat baseline

7. Routine care Intensive treatment BP-lowering Statins Glucose-lowering Baseline Follow up Baseline Follow up Baseline Baseline Baseline Baseline Prescribed treatmentat baseline and follow-up

8. Routine care Intensive treatment BP-lowering Statins Glucose-lowering Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Baseline Baseline Prescribed treatmentat baseline and follow-up

9. Routine care Intensive treatment BP-lowering Statins Glucose-lowering Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Prescribed treatmentat baseline and follow-up

10. Country Hazard Ratio (95% CI) Denmark 0.83 (0.59 to 1.16) 0.80 (0.55 to 1.17) UK 0.96 (0.45 to 2.03) Netherlands Overall (I-squared = 0.0%) 0.83 (0.65 to 1.05) 0.1 0.2 0.5 1 2 Favours intensive treatment Favours routine care Relative risk of composite CVD endpoint as a first event

11. Routine care Intensive treatment Number at risk 1278 1093 879 535 RC 1377 1354 1321 138 1622 1564 1348 1058 624 208 IT 1678 1654 Cumulative probability of composite CVD endpoint 14 p=0.12 12 10 8 Primary composite endpoint (%) 6 4 2 0 0 1 2 3 4 5 6 7 Years of follow-up

12. ADDITION Routine care Danish population with diabetes Danish general population 14 12 10 8 All-cause mortality (%) 6 4 2 0 0 1 2 3 4 5 6 7 Years of follow-up Danish general registry: Carstensen et al. Diabetologia 2008;51:2187-2196 Results in context • Multifactorial intensive treatment was not associated with increased risk of mortality • Mortality in both groups was low

13. Conclusions • Cardiovascular risk factors improved in both groups in the five years following detection by screening • The intervention to promote intensive management was associated with statistically significant but modest differences in prescribed treatment and levels of cardiovascular risk factors • These differences were associated with a non-statistically significant 17% relative reduction in the incidence of a composite cardiovascular event endpoint over five years

14. ADDITION-Europe study team

15. ADDITION study teams • ADDITION-Denmark study group includes Bendix Carstensen, Else-Marie Dalsgaard, Ynna Nielsen, Søren Bech-Morsing, Mette Vinther Skriver, Helle Terkildsen, Morten Charles, Merete Frandsen, Toke Bek and Henrik Andersen • ADDITION-Cambridge study group includes Amanda Adler, Judith Argles, Gisela Baker, Rebecca Bale, Roslyn Barling, Daniel Barnes, Mark Betts, Sue Boase, Ryan Butler, Parinya Chamnan, Sean Dinneen, Pesheya Doubleday, Mark Evans, Tom Fanshawe, Francis Finucane, Philippa Gash, Julie Grant, Wendy Hardeman, Robert Henderson, Garry King, Ann-Louise Kinmonth, Joanna Mitchell, Richard Parker, Nicola Popplewell, A. Toby Prevost, Lincoln Sargeant, Megan Smith, Stephen Sutton, Fiona Whittle and Kate Williams. • ADDITION-Netherlands study group includes Kees Gorter, Paul Janssen, Lidian Izeboud, Jacqueline Berends, Marlies Blijleven, Bart Thoolen, Denise de Ridder, Jozien Bensing, Mehmet Akarsubasi, Paula Koekkoek, Carla Ruis, Geert Jan Biessels, Jaap Kappelle and Michiel van der Linden. • ADDITION-Leicester study group includes Balasubramanian Thiagarajan Srinivasan, David Webb, Laura J Gray, Mary Quinn, Emma Wilmot, Samiul A Mostafa, Nitin Gholap, Hamid Mani, Winston Crasto, Steve Hiles, Joe Henson, Nick Taub, Janet Jarvis, Sukhjit Sehmi, Fiona Ablett, Champa Merry, Emma Healey, Julia Stockman, Sandra Campbell, Janette Barnett, Nil Radia, Mo Radia, Jo Howe, Lesley Bryan, Jane Brela, Jayne Hill, Helen Bray, Rachel Plummer, Zubeir Essat and Francis Pullen