Endoscopic Obesity Therapies
The elephant in the room…
Dr Saurabh Gupta
Visiting Gastroenterologist
Senior Lecturer in Medicine
SAH and Concord Hospital
0562/SAH/1112/SAH
Background
• Over 350 million worldwide are obese (WHO)
• Directly linked to 500,000 deaths per year
worldwide in western countries
• Incidence increased over 800% in last 15 years
• Risk of T2DM increases linearly with
increasing BMI
• Associated co-morbidities include HT, OSA,
NASH (cirrhosis) and arthritis
Obesity related health effects
Obesity in Australia
• Overweight and obesity
will affect 80% by 2025
• Almost 30% adults
obese (BMI>30)
• Economic burden of
obesity
– Overall cost $58 billion
– Direct cost $8 billion
Obesity – an epidemic
“Standard” therapy
Does it work?
• Diet and exercise
• Proprietary weight loss
programs
• Pharmacotherapy
Diet and exercise
• RCT involving 811 overweight individuals
• 7% total body weight loss at 6 months
• Trend to weight regain seen at 12 months
Weight loss programs
• Weight loss minimal compared to control and
education
– Jenny Craig
– Weight watchers
– Optifast/Medifast
– Atkins diet
4.9%
2.6%
4%
0.1-2.9%
Gudzune KA et al. Efficacy of commercial weight-loss programs: an
updated systematic review. Ann Intern Med. 2015;162(7):501–12
Pharmacotherapy with
TGA approval
• Lipase inhibitors
– Orlistat
• Dopaminergic agonists
– Phentermine
• GLP-1 aganoists
– Liraglutide
Pharmacotherapy with
TGA approval
• Weight loss limited to 5-10%
• Side effects concerning
• Mostly approved for short term use
– Long term weight loss data lacking
Kumar RB, Aronne LJ. Efficacy comparison of medications approved
for chronic weight management. Obesity. 2015;23 Suppl 1:S4–7
Weight management in
general practice – The 5 As
1.
2.
3.
4.
5.
Ask
Assess
Advise
Assist
Arrange
Australian Family Physician 2013(42);8:532-41
Ask and assess
Standard care
BMI <25
Active management
BMI 25–29.9
Routinely assess and
Routinely assess and
monitor BMI and waist monitor BMI and WC
circumference (WC)
Discuss if BMI and/or
WC increasing
Screen for and
manage comorbidities
BMI 30–34.9
BMI 35–39.9
Routinely assess and monitor BMI and WC
Discuss health issues
Screen for and manage comorbidities
Assess other factors related to health risk
Blood pressure, lipid profile, fasting glucose, liver
function tests, and ask about symptoms of sleep
apnoea and depression
Australian Family Physician 2013(42);8:532-41
Advise
Standard care
BMI <25
Active management
BMI 25–29.9
Promote benefits of healthy lifestyle
Explain benefits of prevention of
weight gain and maintenance of
healthy weight
BMI 30–34.9
BMI 35–39.9
Promote benefits of healthy lifestyle
Explain benefits of weight management
Australian Family Physician 2013(42);8:532-41
Assist
Standard care
BMI <25
BMI 25–29.9
Active management
BMI 30–34.9
BMI 35–39.9
•Advise lifestyle interventions
•Based on comorbidities, risk factors and weight
history, consider adding intensive weight loss
interventions (eg. VLEDs, pharmacotherapy,
bariatric surgery)
•Tailor the approach to the individual
•Refer to multidisciplinary team for specialist
treatment recommendations. Suitable patients
include those with severe complex obesity for
example those with a BMI >40, BMI >35 with any
serious comorbidity, and those BMI 30–35 with
serious comorbidity and a positive weight
trajectory.
Australian Family Physician 2013(42);8:532-41
Arrange
Standard care
BMI <25
Active management
BMI 25–29.9
BMI 30–34.9
BMI 35–39.9
Review and monitoring
Long term weight management
Referral to specialist weight management
clinic if indicated
BARIATRIC INTERVENTION – SURGERY OR
ENDOSCOPIC
Australian Family Physician 2013(42);8:532-41
Types of bariatric surgery
Vertical Banded
Gastroplasty
Lap adjustable
gastric band
Roux-en-Y gastric
bypass
Types of bariatric surgery
Sleeve gastrectomy
Duodenal switch
Bariatric surgery works!
• RYGB and LSG
• 50-70% EWL at 1 year
• Improvement in co-morbidities
– DM improves/resolves in up to 90%
Buchwald H et al. Weight and type 2 diabetes after bariatric surgery:
systematic review and meta-analysis. AmJMed. 2009;122(3):248–56
Bariatric surgery
What are the risks?
•
•
•
•
Overall mortality
30-day complication rate
Weight regain
Late complications
0.3%
10-17%
20-30%
9-25%
Adams TD et al. Long-term mortality after gastric bypass surgery.
N Engl J Med. 2007;357(8):753
Bariatric Surgery Limitations
• Substantial cost
• Associated morbidity
• Limited to those with
– BMI>40
– BMI 35-40 with
significant comorbidities
• The vast majority have
BMI 30-35
Bariatric Surgery Limitations
• <1% of those who would fit the criteria
actually undergo surgery1
• Weight regain can still be an issue
1. Avidor Y, Still C, Brunner M, Buchwald JN, Buchwald H. Primary
care and subspecialty management of morbid obesity: referral
patterns for bariatric surgery. Surg Obes Relat Dis. 2007;3:392–407
Bariatric endoscopic interventions
Potential benefits of endoscopic
approaches
•
•
•
•
Less invasive
More cost-effective
Lower risk
Can be done as day-only procedure
• Endoscopic procedures have been used as a
“bridge to surgery”
Endoscopic obesity therapy
• Must be:
–
–
–
–
–
Efficacious
Durable
Repeatable
Reversible
Safe
• Modalities include:
–
–
–
–
Space-occupying
Gastric restrictive
Malabsorptive
Regulation of gastric
emptying
– Others
Mechanisms of weight loss
• Prior view of simple restriction vs
malabsorption
• Understanding of more complex physiology
– Neuroendocrine signalling
– GI motility
– ANS signalling
– Bile acid production and absorption
– Gut microbiota
SPACE OCCUPYING DEVICES
Orbera intragastric balloon
Orbera intragastric balloon
•
•
•
•
•
•
Silicone elastomer
Inserted under endoscopic control into fundus
450-700ml saline and methylene blue
Indwell for 6 months
EWL in 2515 patients 33.8%
Improvement/resolution of:
– DM in 87%
– HT in 94%
A. Genco, T. Bruni, S. B. Doldi et
al., “BioEnterics intragastric
balloon: the Italian experience with
2,515 patients,” Obesity Surgery, vol.
15, no. 8, pp. 1161–1164, 2005
Orbera intragastric balloon
• 80% weight loss occurs in first 3 months
• Durability questionable
– Only 25% maintained weight loss at 30 months
• Easily repeated
• Complications include:
– Nausea/vomiting
– Gastric erosion/ulceration
– Spontaneous deflation with risk of obstruction
Other intragastric balloons
GASTROPLASTY TECHNIQUES
Endoscopic sleeve gastroplasty
• Gastric volume reduction technique
• Similar to sleeve gastrectomy
• Endoluminally placed full-thickness sutures
through the gastric wall from the antrum to
cardia
• Multiple devices trialled
Apollo Overstitch
• TGA approved and on the prosthesis list
• Can be used for any tissue apposition
• Reported excess weight loss at 1,3 and 6
months
– 18%, 26% and 30% (10 patients)1
– 29%, 39% and 54% (20 patients)2
1.Lopez-Nava G et al. Endoscopic sleeve gastroplasty for the treatment of obesity.
Endoscopy. Epub 2014 Nov 7.
2.Sharaiha RZ et al. Initial experience with endoscopic sleeve gastroplasty: technical success
and reproducibility in the bariatric population. Endoscopy 2015;47:164-6
Apollo Overstitch
Endoscopic Sleeve Gastroplasty
Apollo Overstitch
PROMISE trial
https://clinicaltrials.gov/ct2/show/NCT01662024
GJ pouch revision
GJ pouch revision
• Enlargement of the gastric pouch or dilatation
of the stoma is independent predictor of
weight regain
• Transoral pouch revision with gastroplasty
(TORe-G) in 20 obese patients
– Median EWL at 3 and 6 mo of 39% and 53%
– No procedure related adverse events
Deepinder Goyal, Rabindra Watson. Endoscopic trans-oral outlet reduction in combination
with gastroplasty (TORe-G) is a novel technique that is highly efficacious and safe for
weight loss in patients with failed Roux-en-Y gastric bypass. American College of
Gastroenterology Annual Meeting Oct 18, 2015
POSE procedure
MALABSORPTIVE PROCEDURES
Small bowel function
• Proximal SI extremely efficient at nutrient
absorption
• Major role in glucose homeostasis
• Enteroendocrine cells sense luminal contents
and release peptides that mediate satiety and
enhance insulin secretin (incretins)
Duodenal-jejunal bypass liner
• Endobarrier (GI Dynamics)
– 60cm impermeable Teflon lining
– Anchored to the duodenal bulb by several barbs
– Easily inserted as ambulatory procedure
– 12 month indwell time
• Aim to mimic RYGB
• Mechanism of action poorly understood
Endobarrier insertion
Endobarrier results
•
•
•
•
•
RCT involving 70 obese patients with T2DM
26 weeks EWL 32% vs 16% in controls
HbA1c 7 vs 8
Device removed at 6 months
EWL 20% vs 11% at 52 weeks
P. Koehestanie et al., “The effect of the endoscopic
duodenaljejunal
bypass liner on obesity and type 2 diabetes mellitus, a multicenter
randomized controlled trial,”
Annals of Surgery, vol. 260, no. 6, pp. 984–992, 2014
Gastroenterology, 2016-04-01, Volume 150, Issue 4, Pages S604-S604
Endobarrier issues
• 20% implantation failure
• Early removal in up to 1/3 patients
– Nausea/vomiting
– Pain
– GI bleeding
• Long term follow up data lacking
• TGA licence revoked Oct 2016
Duodenal mucosal resurfacing
• Radiofrequency ablation of the duodenal
mucosal surface
• Triggers remodelling to “reset”
enteroendocrine cells
• Studies in progress
Revita device
http://www.fractyl.com/medical-professionals/
Magnets in the GI Tract
http://giwindows.com/main-pages/product
Magnetic small bowel bypass
http://giwindows.com/main-pages/product
NAFLD/NASH
• NAFLD affects over 70% with obesity
– 5% will progress to cirrhosis
• NASH cirrhosis projected to be leading
indication for transplant by 2020
NAFLD and Orbera
• 31 patients randomised to Orbera or sham
procedure
– All had hypocaloric diet
• 6 months decrease in BMI
– 1.52 (Orbera) and 0.8 (sham)
• Reduction in:
– Steatosis, body fat composition
steatosis (LS) evaluated through chemical-shift magnetic
– LFT Liver
resonance imaging liver enzymes in morbid obesity; effect of weight loss
obtained with intragastric balloon gastric banding. Acta Diabetol
2014;51:361-8.
Time to embrace the elephant…