1. The ADDITION-Europe study 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 Netherlands Denmark UK 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 0 years~8 years Diabetes detected by screening ~4 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? Background

4. 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 161 practices provided intensive treatment Participants: 1,678 156 practices provided routine care Participants: 1,379 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 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

6. Prescribed treatment at baseline Routine care Intensive treatment StatinsBP-loweringGlucose-lowering Baseline

7. Prescribed treatment at baseline and follow-up Routine care Intensive treatment Baseline Follow up Baseline Follow up Baseline StatinsBP-loweringGlucose-lowering

8. Prescribed treatment at baseline and follow-up Routine care Intensive treatment Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Baseline StatinsBP-loweringGlucose-lowering

9. Prescribed treatment at baseline and follow-up Routine care Intensive treatment Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up Baseline Follow up StatinsBP-loweringGlucose-lowering

10. Relative risk of composite CVD endpoint as a first event 0.10.20.512 Favours intensive treatment Favours routine care Overall (I-squared = 0.0%) Netherlands Denmark UK Country 0.83 (0.65 to 1.05) 0.96 (0.45 to 2.03) 0.83 (0.59 to 1.16) 0.80 (0.55 to 1.17) Hazard Ratio (95% CI)

11. Cumulative probability of composite CVD endpoint 0 2 4 6 8 10 12 14 Primary composite endpoint (%) 01234567 Years of follow-up 137713541321 12781093879535 138RC IT16781654 1622156413481058624208 Number at risk p=0.12 Routine care Intensive treatment

12. Multifactorial intensive treatment was not associated with increased risk of mortality Mortality in both groups was low Results in context 0 2 4 6 8 10 12 14 All-cause mortality (%) 01234567 Years of follow-up ADDITION Routine care Danish general registry: Carstensen et al. Diabetologia 2008;51:2187-2196 Danish population with diabetes Danish general population

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