(Who and) When should patients with obesity and impaired glucose regulation undergo metabolic surgery?

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1 (Who and) When should patients with obesity and impaired glucose regulation undergo metabolic surgery? Alex Miras Senior Clinical Lecturer in Endocrinology

2 Disclosures Fractyl Novo Nordisk Astra Zeneka

3 Edmonton Obesity Staging System (EOSS) Stage 2 co-morbidity Stage 1 moderate moderate Stage 3 Stage 0 Obesity Stage 4 Sharma AM & Kushner RF, Int J Obes 2009

4 EOSS Predicts Mortality in NHANES III Padwal R, Sharma AM et al. CMAJ 2011

5 King s Obesity Staging Score Aasheim E et al, Clinical Obesity 2011

6 Diagrams of the four bariatric/metabolic operations currently in common clinical use. Francesco Rubino et al. Dia Care 2016;39:

7 Current situation Operate on <1% of eligible patients Constantly use BMI to base treatment decisions First come first served Treat healthy obese Treat patients with end-stage disease

8 London underground newspaper

9 NICE guidelines for the surgical therapy of obesity Revised 2014 BMI > 40 BMI > 35 + significant comorbidities BMI T2DM for < 10 years

10 Weight loss Sjostrom L et al, JAMA 2014;311(22)

11 Bariatric Surgery and Long-term Cardiovascular Events

12 Bariatric Surgery and Long-term Cardiovascular Events

13 NBSR - 5 year effects of surgery Miras and Welbourn et al, unpublished data

14 Suggestions Stop using BMI cut offs - keep 30 (or even lower) Define what is a significant comorbidity Establish which comorbidity is improved by surgery in a cost effective manner Compare the cost effectiveness of treating comorbidities Establish predictive markers of comorbidity resolution Healthy obese will have to go to the back of the queue

15 Moving from weigh to sugar Dixon 2008 JAMA Mingrone 2012 NEJM Schauer 2012, 2014 NEJM

16 NICE guidelines for the surgical therapy of obesity Revised 2014 BMI > 40 BMI > 35 + significant comorbidities BMI T2DM for < 10 years

17 NICE guidelines for the therapy of T2DM Type 2 diabetes in adults: management, NICE guideline NG28 (December 2015)

18 HbA1c after metabolic surgery compared with medical treatments in published RCTs Among the RCTs, the most common predictors of diabetes remission included: duration of diabetes requirement for insulin disease status (HbA 1c ) Philip R. Schauer et al. Dia Care 2016;39:

19 Forest plots from a systematic review and meta-analysis of all published articles reporting T2DM remission rates following bariatric/metabolic surgery. BMI<35 Remission 72% BMI 35 Remission 71% David E. Cummings, and Ricardo V. Cohen Dia Care 2016;39:

20 Algorithm for the treatment of T2DM, as recommended by DSS-II voting delegates Francesco Rubino et al. Dia Care 2016;39:

21 Diabetes Remission in the SOS Sjostrom L et al, JAMA 2014;311(22)

22 Predictors of remission in the SOS Duration of diabetes Weight change at 2 years Not BMI Sjostrom L et al, JAMA 2014;311(22)

23 Microvascular complications Sjostrom L et al, JAMA 2014;311(22)

24 Macrovascular complications Sjostrom L et al, JAMA 2014;311(22)

25 Predictors of micro and macro-vascular complications Diabetes < 1 year Diabetes 4 years Sjostrom L et al, JAMA 2014;311(22)

26 Prevention of diabetes SOS study Carlsson LM at al, NEJM 2012

27 Reduction in microvascular complications A: normal glycaemia B: Prediabetes C: New T2DM D: Established T2DM Mingrone 2012 NEJM Carlsson et al, Lancet D&E 2017

28 Conclusion so far Data say: We should be operating on patients with pre-diabetes or as early as possible in their diagnosis of T2DM In practice: Really?

29 Liraglutide and Body Weight Pi-Sunyer X et al. N Engl J Med 2015;373:11-22

30 Liraglutide and glycaemia Pi-Sunyer X et al. N Engl J Med 2015;373:11-22

31 Liraglutide for CV events in diabetes Marso SP et al. N Engl J Med 2016.

32 Empagliflozin: Cardiovascular Outcomes and Death Zinman B et al. N Engl J Med DOI: /NEJMoa

33 Empagliflozin and kidneys Wanner C et al. N Engl J Med 2016;375:

34 Suggestions If the patient has multiple comorbidities and also happen to have pre-diabetes or early diabetes - operate (obesity surgery) If the patient just has T2DM - work with non-surgical treatments When you see insulin coming - operate, prioritise (metabolic surgery) In advanced T2DM (when you are stuck) - still operate but expect less; do not prioritise

35 Acknowledgements Imperial College London Steve Bloom Tricia Tan Anna Kamocka Belen Pevida Madawi Aldhwayan Harvinder Chahal Samantha Scholtz Ahmed Ahmed Sanjay Purkayastha Krishna Moorthy Julian Teare University of Dublin Carel W le Roux Neil Docherty University of Surrey Margot Umpleby Barbara Fielding Fariba Shojaee-Moradie Nicola Jackson Florida State University Alan C Spector King s College London Francesco Rubino Ameet Patel Simon Aylwin Royce Vincent King Saud University, Saudi Arabia Ghalia Abdeen University of Zurich Marco Bueter University of Wurzburg Florian Seyfried

36 Morbidity and weight loss sensitivity or resistance Metabolic Ventilatory Reproductive CV risk Perceived health status Eating behaviour % weight loss to improve morbidity ADL / QoL Anxiety / depression Body Image dysphoria Economic cost Aylwin 2005

37 Liraglutide and the liver Armstrong et al, Lancet D&E 2016

38 Targeting the Kidney Chao EC, et al. Nat Rev Drug Discovery. 2010;9: