Presentation by Josep Vidal, Endocrinology and Nutrition Department Institut de Malaties Digestives i Metabòliques Hospital Clínic Barcelona, Spain during ECIPE Roundtable: Fighting the Burden of Obesity, Brussels 07/02/2017

1. Trea%ng Obesity: The Way Forward
Josep Vidal
Endocrinology and Nutri0on Department
Ins0tut de Malal0es Diges0ves i Metabòliques
Hospital Clínic Barcelona, Spain

2. “EU Obese Subjects Box”
Health at a Glance: Europe 2016
Trea0ng Obesity: The Way Forward
Prevalence Obesity in EU Member States
The preven0on
strategy
2011
2014

3. Health at a Glance: Europe 2016
Prevalence Obesity in EU Member States
2011
2014
The treatment
strategy
Trea0ng Obesity: The Way Forward

4. Condi%ons associated with obesity
Up to 195 condi0ons have been associated with obesity
Trea0ng Obesity: The Way Forward
These condi0ons
would be less
common shall
obesity be less
prevalent

5. The End Organ Damage Approach
Current Approach to Obesity Related Condi0ons

6. Therapeu0c Algorithm for Type 2 Diabetes
European Associa%ons for the Study of Diabetes (EASD)
• Focus on drug combina%ons for glycemic control
• Considera%on of weight loss as desirable side effect of hypoglycemic drugs
• No specific strategies for weight loss

7. The End Organ Damage Approach
Current Approach to Obesity Related Condi0ons
Is this the logical
approach?

8. The Common Ground Approach
Impact of MODEST weight loss on obesity-related comorbidi%es
(% weight loss associated with improvement of different condi0ons)
Weight loss and Obesity Related Comorbidi0es
0 2 4 6 8 10 12 14 16
Metabolic syndrome
Pre-diabetes
T2 diabetes
Hypertension
NAFLD
OSA
Asthma
Urinary incon0nence
Weight loss rela0ve to baseline Garvey et al. End Prac:ce 2016

9. Weight loss and Obesity Related Comorbidi0es
Obesity-related cancers
Incidence and mortality reduced
Doesn’t this op%on
deserve further
aZen%on?
The Common Ground Approach
Impact of LARGE weight loss on obesity-related comorbidi%es

10. Weight Loss at 1 Year with High-Intensity Lifestyle Interven%ons or Pharmacotherapy Combined
with Low-to-Moderate-Intensity Lifestyle Counseling.
Heymsfield SB, Wadden TA. N Engl J Med 2017
Not approved by the EMA
Not approved by the EMA
Current Op0ons for a Weight Centered Approach

11. The Look Ahead Trial
(RCT: intensive LII versus control group in 5145 subjects with T2D, and BMI 36 kg/m2)
High Intensity Lifestyle Interven0on in pa0ents with Diabetes
Weight Changes
Ini0al benefits of current lifestyle interven0ons are difficult to sustain
The Look Ahead Research Group. N Eng J Med 2013
Fitness Changes

12. The Look Ahead Trial
(RCT: intensive LII versus control group in 5145 subjects with T2D, and BMI 36 kg/m2)
High Intensity Lifestyle Interven0on in pa0ents with Diabetes
DM remission over 4 years
Posi0ve impact of WL but limited because
of weight regain
Gregg EW et al. JAMA 2012
Is MODEST weight loss worthless in T2D?
The Look Ahead Research Group. N Eng J Med 2013
Changes in the incidence of CV disease

13. The Look Ahead Trial
(RCT: intensive LII versus control group in 5145 subjects with T2D, and BMI 36 kg/m2)
High Intensity Lifestyle Interven0on in pa0ents with Diabetes
Post-hoc analysis based on the achievement of >10% WL irrespec%ve of the study group
The Look Ahead Research Group. Lancet 2016
0.4
0.6
0.8
1
1.2
1.4
1.6
<2% loss 2-5% loss 5-10% loss >10% loss
p=0.034
Adjusted Hazard ra%o (95% CI)
Incidence of CVD at 10 y
Weight Loss Category at 1 y follow up
1.00 1.08
1.16
0.79
0
10
20
30
40
50
<2% WL 2-5% WL 5-10% WL > 10% WL
Distribu%on of WL categories
% ILI 18% 47% 75% 92%
% cont 82% 53% 25% 8%
• Posi0ve impact of WL on CVD, if >10% WL is achieved
• Importance of iden0fying responders and factors associated
with ↑ likelihood of >10% WL

14. Fujioka et al. Diabetologia 2014;57(Suppl. 1):Abstract 904-P
63.1
27.1
33.1
10.6
49.6
23.7 24.8
9.9
0
20
40
60
80
Liraglu0de Placebo
>5% WL-12 m
>10% WL-12 m
>5% WL-36 m
>10% WL-36 m
Scale Prediabetes Trial
An0-Obesity Drugs Study Subjects (%)
• Effec0ve in facilita0ng the
achievement of WL goals

15. Weight Loss at 1 Year with Bariatric Surgery and Lifestyle Interven%ons as Compared with
Lifestyle Interven%ons Alone.
Bariatric Surgery
Heymsfield SB, Wadden TA. N Engl J Med 2017

16. Bariatric Surgery and Type 2 Diabetes
-0.6±2.5%
-2,5±1,9%
-2,5±2,1%
STAMPEDE Trial-Cleveland Clinic: 3 years FU
(n=137, Age 48 y, BMI 36,5 kg/m2, HbA1c preQ 9,3%, DM dura0on 8,3 y, Insulin Rx 43%)
Schauer et al. N Eng J Med 2014
Time course of HbA1c Time course of Body Mass Index

17. Sjostrom L, J Int Med 2013
Swedish Obese Subjects Study
Control, n=2037; Bariatric Surgery, n= 2010 (>10 years follow up)
1. Major and sustained weight loss compared to conven0onal treatment
2. Reduc0on of all cause mortality
3. Reduc0on of cardiovascular mortality and incidence of 1st CV event (fatal or no fatal)
4. Preven0on and remission of diabetes
5. Reduc0on of the incidence of myocardial infarc%on in subjects with T2D
6. Reduc0on of obesity-related cancer incidence and mortality (in women)
7. Improved quality of life
8. Reduc0on of health costs (up to 20 years follow up)
Health Benefits Associated with Bariatric Surgery

18. Approaching an overwhealming task
Too many pa0ents!
BMI in the obesity range
Health
Impact
Concentrate on Those with the
Greatest Health Impact
Trea0ng Obesity: The Way Forward

19. Summary
• Tackling the obesity epidemics requires ac0on beyond preven0on
• Trea0ng obesity is an effec0ve means to improve obesity-related
comorbidi0es
• Efforts should be made to make effec0ve therapies available to
obese subjects with obesity-related comorbidi0es
– Although high-intensity lifestyle interven0ons are effec0ve, research is
needed to beler uon how make these interven0ons feasible
– More research is needed to substan0ate the benefits of drug-assissted
weight loss
– Efforts should be made to make bariatric surgery to eligible pa0ents