Introduction

General weight loss results

5% reduction in body weight is clinically significant for weight loss and is associated with improved quality of life and better glycaemic control

10-15% body weight loss is effective to control medical co-morbidities associated with obesity such as HPT, OSA, PCOS and depression

Anti-obesity medications and injections aim to produce about 10-15% weight loss

• 5 months of Semaglutide have reported 10.6% weight loss
• 9 months of Tirzapatide have reported 21.1% weight loss
• Once these injections are stopped, most patients regained half that weight within the first year

Bariatric surgery (sleeve gastrectomy and gastric bypass) can offer over 30% weight loss results in the first year

• Bariatric surgery offers the better sustained, long term weight loss results and resolution of medical co-morbidities
• Bariatric surgery has been reported to help patients maintained 25% total body weight loss up to 10 years after surgery

Caveats of weight loss medications and surgery

But losing weight is challenging and maintaining weight loss is even more difficult.

• Once the GLP-1 injections stop, there is a high risk for weight regain
• Successful weight loss may only be 20-30% from the baseline pre-surgery weight in the long term

Some studies reported that 20-50% of patients who undergo surgery may have inadequate weight loss (IWL) or weight regain

• IWL has been defined as <50% expected weight loss by 18months post op
• Weight regain has been defined as weight increase by >50% from the peak weight loss attained after bariatric surgery

Obesity is now regarded as a chronic relapsing disease and the cause is multi factorial

Weight regain can occur with time with all types of bariatric surgery

• Weigh regain resulting in a total net loss of 5% pre-operative weight has been reported in 3/3% of patients after RYGBP and 12.5% of patients after a sleeve gastrectomy 5 years after surgery

• After 10 years 30% of patients reported losing <20% of their pre-operative weight and 40% of patients have <50% excess weight loss (EWL)

One of the more acceptable indications for revision surgery include reflux or complications of sleeve gastrectomy and for remission of T2DM

However in general revision bariatric surgery are less effective as primary procedures, the risk and complications rate of revision surgery are much higher

• Post op morbidity rate reported to be 4.6% (compare to 2% for primary procedures)

Medications available for weight loss Phentermine                           Duromine Naltrexone/Bupropion            Contrave Orlistat                                    Xenical Liraglutide                               Saxendra Semaglutide                            Ozempic, Wegovy, Rybelsus Tirzapetide                              Mounjaro, Zepbound Please note: Currently (2024) in Australia Topiramate is not available for weight loss Tirzapetide is not yet approved for weight loss or for weight maintenance after bariatric surgery   In the future there may be more alternatives such as: GLP1-RA combine with Amylin Oral GLP1-RA (Orforglipron) Cagrilinitide + Semaglutide (CadriSema) Triple hormone therapy Retatrutide (GIP, GLP1-RA and Glucagon)

Phentermine-topiramate, naltrexone-bupropion and orlistat may result in 5kg weight loss

Bupropion/naltrexone may be used in patients with depression, with up to 6.1% body weight loss achieved

GLP-1 receptor agonist injections Background *GLP-1 analog acts by inhibition of gastric emptying, reduction of appetite, regulation of satiety through the central nervous system pathways to reduce calorie intake  *These injections were initially developed for the treatment of T2DM (lowering HbA1C, improving B cell function), weight management (5-10% TBWL) and improving control of systolic hypertension  *There is also evidence that these GLP-1 receptor agonist may help in post bariatric surgery hypoglycaemia Both Liraglutide and Semaglutide have safe and effective weight loss result associated with improvement in cardiovascular risk profile in patients with T2DM Semaglutide have better weight loss outcome compared to Liraglutide including patients without T2DM Both of the above has also been used in patients after bariatric surgery with reported good meaningful short term weight loss results Side effects of GLP1-RA *Reported non serious side effects include early satiety, reflux, nausea, vomiting, constipation, diarrhoea in 10-50% of patients *Pancreatitis has been reported in 0.3% *However there are also report loss of lean muscle fat free mass (FFM) and bone mineral density (BMD) in patients receiving Liraglutide

GLP-1 receptor agonist injections Liraglutide 3mg/day has up to 8% body weight loss after 1 year from the SCALE (Satiety and Clinical Adiposity Liraglutide Evidence) study Semaglutide 2.4mg/week from the STEP (Semaglutide Treatment Effect in People with Obesity) in the RCT STEP 4 and STEP 5 showed significant (up to 16% body weight loss) and enduring weight loss at 1 and 2 years One trial reported the success rate for Liraglutide to be 7.4% weight loss over 56 weeks vs Semaglutide 14.9% weight loss after 64 weeks GLP-1 receptor agonist after bariatric surgery These medications may be used in some patients with inadequate weight loss or weight regain after bariatric surgery Liraglutide 1.8mg daily dose resulted in >5% weight decrease from baseline, achieving 6kg weight loss after 6 months (range 6 to 13kg over 6 to 24 months) or 5-10% over 6 to 12 months Semaglutide was found to be superior to Liraglutide with regard to weight loss after bariatric surgery, achieving >15% after 6 months and >10% after 12 months of the injections Overall both consistently exhibit efficacy in facilitating weight loss of 5 to 17% in patients with suboptimal weight loss after bariatric surgery Combined GIP/GLP1-RA medication Tirzepatide is a novel glucose depent insulinotrophic polypeptide and glucagon-like peptide receptor agonist (GIP/GLP1-RA) has been shown to be the most effective medication for treatment of obesity with acceptable safety profile A RCT showed 20% total weight loss with the 15mg weekly injections One study of Tirzepatide used for weight regain after sleeve gastrectomy reported 15.5% weight loss at 6 months (compared to Semaglutide 10.3% at 6 months) Tirzepatide has been shown in RCT to result in the most significant weight loss in the treatment of obesity Results of the STEP1 and SURMOUNT1 comparing Tirzapetide 10-15mg to Semaglutide 2.4mg found that Tirzapetide is more likely to achieve 5% weight loss However the durability of the treatment is not known beyond 6 months Results from the STEP4, STEP1 trial extension and SURMOUNT4 showed significant weight regain after withdrawal of the treatment These medications can also be very costly

Intra gastric balloon

Temporary and minimal invasive procedure with good short term efficacy

• Action is a combination of restriction (decreased stomach reservoir capacity), delayed gastric emptying, increase early and prolonged satiety and may have some ghrelin effect

This is mainly for patients who does not meet the criteria for bariatric surgery or as a bridge to bariatric surgery for the high risk super obesity patients

Balloon is in place for 6 or 12 months

• Some reported TBWL >10% and EWL > 25% when the balloon is removed (no data is available for the longer term)
• The failure rate is <25%

Risks include

• The early removal rate due to intolerance is <5%
• The complication risk is generally quoted as <1%, some patients may get gastric ulcers or bleeding
• The most serious risk is oesophageal or gastric perforation, which is quoted as <0.1%

Endoscopic sleeve gastrectomy (ESG)

• This is not a new therapy for weight loss but so far there has not been a lot of uptake in Australia
• The ESG may have good results for some patients and have better weight loss results than the balloon
• This procedure may be appropriate/suitable for patients who are not surgical candidates

Endoscopic suturing and plication (ESG) result in 17% TBWL at 12months with low adverse rate

ESG is repeatable, convertible, scalable and may have the same impact on metabolic disease

How to choose Medications for weight loss The Step-1 trial (Semaglutide 2.4mg) showed 14.9% TWL after 68 weeks 86.4% of the patients achieved >5% TWL The Surmount-1 trial (Tirzepatide 15mg) showed 20.9% TWL after 72 weeks 91% of the patients achieve >5% TWL 57% of the patients achieved >20% TWL However there are severe limitations with the availability of the GLP-1 injections and the cost in the long term There may be more side effects emerging with time as more patients are being prescribed these injections Endoscopic procedures for weight loss The Essential trial (POSE Primary Obesity Surgery Endoluminal Procedure) has 4.95% of total weight loss 41.5% of the patients with Class 1 and 2 obesity achieved >5% TWL However these endoscopic procedures are not commonly performed, may have limited weight loss results and it is difficult to convert them to surgery in the future Bariatric and metabolic surgery Surgery offers the most successful long term weight loss result and resolution of medical co-morbidities for patients with lass 3 (morbid) obesity However surgery is the most aggressive option because surgery is drastic, not reversible, have side effects, risk and complications Revision surgery is becoming more common with the passage of time with complications, such as hiatus hernia, reflux and weight regain (in about 20-35% of patients within 2 to 6 years) The is a higher revision rate after gastric band and sleeve gastrectomy for weight regain

Patient selection

Obesity is a chronic disease and is a biological disease

Weight loss results are unpredictable and varies amongst individuals

• The patients are in a heterogenuous group with significant differences in outcome even after having the exact same operation

Some generalizations can be made but each patient should be assessed properly by their GP, specialist and dietitian first

• Young females in the reproductive age group tend to prefer a lesser aggressive option such as anti-obesity medications or sleeve gastrectomy
• Patients in the lower BMI group who are concerned about long term side effects and complications of the gastric bypass or other types of bypass procedures tend to prefer the sleeve gastrectomy
• Severely obese patients (BMI 50 or higher) with T2DM and metabolic syndrome usually prefer to have a gastric bypass procedure
• Patients with severe acid reflux and Barrett’s oesophagus are usually recommended to have the Roux Y gastric bypass
• Very severely obese patients with high anaesthetic risk may prefer to have a 2 stage procedure with a sleeve gastrectomy first

But patient selection for which intervention (medication, endoscopy or which type of surgery) is difficult which requires a lot of research and consideration

• Many factors which include genetics, biological/physiological, behavioural and psychological factors may contribute to suboptimal results after interventions for obesity