In the last year modern pharmacotherapy such as Semaglutide (Ozempic, Wegovy) and Tirzapatide (Mounjaro) have received a lot of attention

With regards to patients having metabolic and bariatric surgery as a primary procedure or revision surgery The IFSO expert panel and Delphi consensus in 2024 reported that   There is evidence that 5% or more weight loss has shown metabolic improvements *Obviously greater weight loss has shown broader clinical benefits with significant reduction in mortality   At the present time there is insufficient high level evidence to recommend routine use of obesity management medications (OMM) before metabolic bariatric surgery, more research is needed *The decision to use OMM before surgery should be personalised to determine the most appropriate strategy for individual patient *The GLP-1 injections should be discontinued before surgery to minimise peri-operative risk   After metabolic and bariatric surgery, treatment with OMM should be withheld until the achievement of weight plateau unless there is a need to initiate them earlier *Future research is needed to identify predictors of which patients are likely to derive substantial benefit from combined pharmaco-surgical therapy for obesity and its complications   Both metabolic bariatric surgery and GLP-1 reception agonist injections is strongly associated with reduced adverse cardiovascular events *Future research is required to determine the benefits of combination treatment for these outcomes   Both metabolic bariatric surgery and GLP-1 RA reduce chronic renal disease *Future research is required to determine the benefits of combination treatment for these outcomes   In patients with suboptimal outcome initial clinical response after metabolic bariatric surgery, the addition of OMM can improve metabolic outcomes   For patients requiring OMM to maintain healthy weight after metabolic bariatric surgery, the ongoing use of the medication is likely needed *Research on the intermittent OMM use and/or dose adjustment after surgery for a suboptimal clinical response is needed   The benefit of endoscopic therapies for obesity can be enhanced by combination with OMM   Patients with a suboptimal initial clinical response (SICR) or recurrent weight gain (RWG) after metabolic bariatric surgery should be informed of all available evidence based treatments, including their benefits and risks   In patients with suboptimal initial clinical response or recurrent weight gain after metabolic bariatric surgery, different options including OMM, endoscopic therapies, revisional/conversion surgery can be considered     There is emerging evidence that weight loss induce by OMM is similar among people who have or have not undergone metabolic bariatric surgery   When used after surgery there appears to be no increase incidence of side effects from the OMM compared to the non surgical cohorts   However the long term efficacy and safety of OMM after metabolic bariatric surgery is unknown *Studies are needed to understand the value and limitations of such combined therapy   End points of future clinical trials of existing and/or novel obesity management interventions (behavioural, pharmacological, endoscopic and surgical) should focus on improvement, remission and prevention of clinical manifestations and complications of obesity in addition to weight loss   For patients with recurrent weight gain, treatment with OMM should be considered before revisional surgery   When treatment with OMM after metabolic and bariatric surgery results in suboptimal initial clinical response or when there is an inability to continue medications (due to cost or adverse reaction), then endoscopic, revisional or conversion surgery should be considered   Healthcare systems need to support the long term management of obesity, as they do for other chronic disease (such as diabetes and cardiovascular disease)   All healthcare providers need a basic understanding of the complex aetiology, pathophysiology and evidence based management of obesity   Studies on the cost effectiveness of the association of modern pharmacotherapy and metabolic bariatric surgery are essential to determine the role of pre-operative and post operative OMM

IFSO Pharmacotherapy for recurrent weight gain after bariatric surgery IFSO statement 2024 Pharmacotherapy should be included in the multi disciplinary treatment plan for recurrent weight regain (RWG) *However the timing to initiate pharmacotherapy or the duration of use is not known *There is no data on the use of obesity management medication before patient reached their plateau after bariatric surgery   Obesity management medications include oral tablets (phentermine, topiramate) individually or in combination can reduce RWG after RYGBP *There is a report of 30.3% of patients losing >10% TWL *Topiramate is the only medication that demonstrated statistically significant response for weight loss *The weight loss response rate is less for patients who had the sleeve gastrectomy compared to RYGBP     Obesity management medications with GLP-1 RA injections showed good results in the short term *With liraglutide 3mg/day for 12 months there is a loss of 5% TWL (for 75% of patients) and 10% TWL (for 25% of patients)   The GRAVITAS is a randomized control trial (RCT) trial using liraglutide 1.8mg/day vs placebo in patients with persistent or recurrent T2DM 1 year after sleeve or RYGBP *Patient on liraglutide lost more weight and has better glycaemic control than placebo   Another small RCT add liraglutide early on after sleeve gastrectomy compared to placebo *Liraglutide added early after LSG significantly augments weight loss   The Bari-Optimise RCT recently published the efficacy and safety of liraglutide 3mg vs placebo for patients with <20% TWL after sleeve or RYGBP *Liraglutide 3mg for 24 weeks led to significant reduction in %TWL compared to placebo with improve cardio-vascular risk factors and quality of life   Currently there are very few results with Semaglutide in trials for SICR and RWG after bariatric surgery, there will be more publications in the future *One trial reported semaglutide 0.5mg/week to have a mean of 10.3% TWL (85% of patients achieve >5% TWL after 6 months)   Semaglutide phase 3 trial STEP-1 reported 2% reduction in body weight within the first 4 weeks of treatment (early responders) and these patients continue to lose weight throughout the 6 month follow up period     One study of GLP-1 RA therapy for RWG 12 months after bariatric surgery reported a median 8.8% TWL after 6 months *>3/4 patients lost over 5% baseline weight, >1/3 lost over 10% baseline weight *The median patient lost 67.4% of the weight regained (but not 100%) after bariatric surgery

IFSO 2024 summary of expert opinion 1. Metabolic and bariatric surgery Bariatric metabolic surgery has been performed for many decades *with a robust body of evidence supporting long term efficacy, durability and cost effectiveness *is still the gold standard for treatment of morbid obesity and obesity related medical co-morbidities in terms of long term optimal weight loss, improvement in health related quality of life and reduction in obesity related mortality or all cause mortality *after gastric bypass surgery the post prandial release of GLP-1 is intermittent Pharmacotherapy is emerging and is in its early phase at the moment *not many have long term studies beyond 5 years *after pharmacotherapy there is continuous stimulation on the GLP-1 receptor, long term side effects is still unknown 2. Subcutaneous injections for weight loss Modern pharmacotherapy has changed the landscape of the treatment of obesity and its complications in the last year However there is a wide knowledge gap regarding the important points in contemporary obesity treatments *Future studies need to include weight loss and remission/improvement of obesity complications outcome regarding the added benefits of metabolic bariatric surgery plus obesity management medications Obesity management medications should not be viewed as a competitor to or replacement for metabolic and bariatric surgery, the mechanisms may be similar or slightly different GLP-1 receptor agonist such as liraglutide (Saxendra) and semaglutide (Ozempic, Wegovy) as well as the dual GIP/GLP 1 RA tirzapatide (Mounjaro) are available in Australia *These agents have demonstrated weight loss ranging from 5 to 15% along with significant reductions in cardio metabolic risks *Trials for liraglutide (SCALE), for semaglutide (STEP, SUSTAIN, PIONEER) and tirzapatide (SURMOUNT, SURPASS) are ongoing Currently it is recommended that for patients using the GLP-1 RA should complete at least 12 weeks of continuous therapy to achieve clinically meaningful weight loss with corresponding health benefits However there may be issues with patient adherence to the injections due to factors such as cost, supply issues and side effects Discontinuation of pharmacotherapy was associated with weight regain of 2/3 of the weight loss and loss of the benefits on cardiometabolic risk factors within 1 year Currently the major issue is the long term cost effectiveness and supply chain issues

New perspective A change in the approach to metabolic bariatric surgery + post op weight loss injections Currently there is definitely a paradigm shift in terms of understanding visceral/central obesity (similar to Type 2 diabetes mellitus) and its metabolic impacts on health Obesity should be regarded as chronic long term multifactorial and multi stage disease *Obesity management medications should be considered a requirement for the longer term (not just a few months or a year) *Obesity surgery should be regarded as integral to the subgroup of patients who meets the criteria for metabolic and bariatric surgery In the future there may/will be more evidence for the combined treatment for obesity with both metabolic bariatric surgery and GLP-1 RA medications in a synergistic or adjuvant role to integrate both into the management for obesity