Background Bariatric interventions offer a more efficacious and durable weight loss than non-surgical approaches Surgical weight loss procedures are limited by appeal, availability, cost and short and long term risks Endoscopic Sleeve Gastroplasty is an incisionless, minimally invasive technique Treatment Target Clinically significant improvements in obesity related co- morbidities are higher when %TBWL exceeds 10%. (lifestyle intervention typically results in 3-5% TBWL)

Procedure ESG reduces the volume of the stomach (~80%) using a series of endoscopic sutures (5- 9x) The final shape of the stomach resembles a traditional sleeve without the need to amputate the greater curvature, thus less invasive

Patient Selection and Exclusion Recommendations Age: 18-65+ BMI: 30-45kg/m2 (BMI is not limited to 45. The IFSO/OSSANZ bariatric guidelines are followed) Compliant with prescribed diet, aftercare instructions Exclusion Recommendation Family history of Stomach Cancer Hiatus hernia >5cm Previous gastric surgery Gastric ulceration Cirrhosis Pregnancy or plans of pregnancy in the next 12 months Coagulation disorders or chronic use of anticoagulants*** Any active medical condition that would preclude a safe endoscopic suturing repair ***at the discretion of the treating physician

ESG for Obesity: a Multicenter Study of 248 patients with 24-months Follow-Up Mean age 44y, 73% female. Baseline BMI 37.8 (+/- 5.6 Kg/m2) Results Weight Loss (%TBWL) 6-months 15.2% (95% CI 14.2- 16.3) 24-months 18.6% (95% CI 15.7- 21.5) Lopez-Nava et al. Obes Surg Apr 2017

Endoscopic Sleeve Gastroplasty; 1-year Follow-Up Results Changes in weight loss post ESG Adverse Events No major events or bleeding complications Post discharge pain 50%, and nausea 20% Variable 1-month 3-months 6-months 12-months BMI loss (kg/m2) 2.8 +/- 0.8 4.9 +/- 1.6 6.9 +/- 2.9 7.3 +/- 4.2 Total Weight loss 7.9 +/- 2.7 14.1 +/- 5.5 19.6 +/- 9.1 21.1 +/- 12.6 % TBWL 7.4 +/- 2.3 12.9 +/- 4.3 17.8 +/- 7.5 18.7 +/- 10.7 % EBWL 24.0 +/- 11.8 40.5 +/- 16.5 53.9 +/- 24.8 54.6 +/- 31.9 Lopez-Nava et al. End Int 2016

Endoscopic Sleeve Gastroplasty Improvement in Metabolic Syndrome Pre-ESG, mean (SD) 12-month post ESG, mean (SD) P-value HbA1C, % 6.6 (1.2) 5.6 (0.5) 0.002 Waist Circ, cm 119.7 (14.1) 92.8 (5.9) <0.001 SBP, mmHg 129 (13) 122 (13) 0.02 LDL, mmol/L 3.1 (1.0) 3.2 (0.4) 0.79 TG, mmol/L 1.5 (0.9) 1.0 (0.4) 0.017 ALT, iU 32 (16) 20 (11)

Endoscopic Sleeve Gastroplasty; 1-year Follow-Up Endoscopic view, 1-year post ESG Barium study, 1-year post ESG. Arrows show suture plications Lopez-Nava End Int 2016

Short term Outcomes of ESG in 1000 consecutive patients A. Alqahtani et al (Suadi) GASTROINTESTINAL ENDOSCOPY in-press, 2019

ESG: Outcome N=1000. Mean BMI 33.3 +/- 4.5Kg/m2. Age 34.4 +/-9.5 yr. 89.7% female Operating time 82 +/- 20min (procedure 61 +/- 16min) Mean 4.2 +/- 0.5 sutures Percentage excess weight loss after ESG

ESG: Metabolic Outcomes N=4 N=14 N=28 N=13 N=18

ESG complications Abdominal pain and nausea 92.4% N=2 required blood t/f

Comparison with Surgical procedures.

Background: ESG vs LSG Laparoscopic sleeve gastrectomy is the most common bariatric procedure; 58.1% of the 216,000 bariatric procedures performed in US 2016 Complication rate 13%, and a 9% re-operation rate Leak rate 1.21%, PE 0.25% Development of GER 21% (conversion surgery in 2.9%).

Results: ESG vs LSG Subgroup Analysis: (BMI >40Kg/m2 vs BMI<40kg/m2) BMI >40kg/m2: %TBWL in ESG group remains significantly lower than LSG (coefficient -8.25; p<0.001) BMI <40Kg/m2: %TBWL in ESG group borderline significantly lower than LSG (coefficient -2.98, p=0.05) V Kumbhari et al. Gastrointest. Endosc. 2018 Aug 24  

Results: ESG vs LSG Adverse Events ESG significantly lower rate of adverse events than LSG (5.2% vs 16.9%, p<0.05). All ESG patients were discharged on the same day. Re-admission: GI bleeding (2), Perigastric fluid collection (1). All conservative management LSG patients: hypotension (1), transfusion (2), dehydration (1), abdominal pain (2), intractable N&V (3), GI bleed (1), acute pancreatitis (2) New Onset GERD: ESG 1.9%, vs LSG 14.5%, (p<0.05) V Kumbhari et al. Gastrointest. Endosc. 2018 Aug 24

Endoscopic Sleeve Gastroplasty ESG is an effective and durable treatment for weight loss Weight loss at 2 years ~16-20% TBWL Lower morbidity than surgical treatments

Conclusions A multidisciplinary and population based approach is required. - Diet, exercise and behavioural management - ?Pharmacologic treatments - Intragastric Balloon: ?long term efficacy - Endoscopic treatment: Endoscopic sleeve gastroplasty vs Surgical treatment