Despite the huge interest in the newer generation of obesity management medications (OMMs), there is limited knowledge about the impact they can have on metabolic and bariatric surgery patients before, concomitant with and after surgery. At the recent IFSO Consensus Meeting in Vienna, Austria (30 April - 1 May), an international group of multidisciplinary experts in the fields of endocrinology and surgery, presented and discussed the current evidence with the aim of developing a set of evidenced based recommendations. Here is a summary of the presentations.
Module 1 – Use of OMMs before MBS
How much weight loss do we need for health?
In the opening presentation, Professor Carel le Roux (University College Dublin, Ireland) said that obesity is associated with multiple complications including metabolic, mechanical and mental. The evidence shows that weight loss has been shown to improve many of the complications of obesity as progressive weight loss with calorie restriction has dose-dependent & tissue-dependent biological effects. He said the question then becomes ‘how much weight loss leads to such improvements?’
For example, the Finnish diabetes prevention study (Tuomilehto J, et al. Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801. PMID: 11333990) demonstrated that the risk of diabetes was reduced by 58% (p<0.001) by changes in the lifestyles of patients with prediabetes. Furthermore, the XENDOS study (Torgerson JS, et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004 Jan;27(1):155-61. doi: 10.2337/diacare.27.1.155. Erratum in: Diabetes Care. 2004 Mar;27(3):856. PMID: 14693982) reported that compared with lifestyle changes alone, which was similar to the Finnish Diabetes Prevention Study, orlistat plus lifestyle changes resulted in an additional 60% reduction in the incidence of type 2 diabetes over four years and produced greater weight loss in a clinically representative population of people living with obesity.
The DiRECT study by Thom G et al (Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT). Diabet Med. 2021 Aug;38(8):e14395. doi: 10.1111/dme.14395. Epub 2020 Sep 27. PMID: 32870520) identified weight loss as the strongest predictor of remission at 12 months and 24 months, with weight loss of 15 kilograms and 15% weight loss equally good predictors of achieving remission of type 2 diabetes. In addition, the LOOK AHEAD study (Wing RR et al. Look AHEAD Research Group. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011 Jul;34(7):1481-6. doi: 10.2337/dc10-2415. Epub 2011 May 18. PMID: 21593294; PMCID: PMC3120182), found that even 7% weight loss were associated with significant improvements in CVD risk factors (glycemia, blood pressure, triglycerides, and HDL cholesterol but not with LDL cholesterol) at one year, but larger weight losses had greater benefits. A later paper from the LOOK AHEAD group (Gregg EW et al. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2016 Nov;4(11):913-921. doi: 10.1016/S2213-8587(16)30162-0. Epub 2016 Aug 30. PMID: 27595918; PMCID: PMC5094846) suggests an association between patients who achieved >10% weight loss and reduced incidence of cardiovascular disease events (eg. non-fatal acute myocardial infarction, non-fatal stroke, or admission to hospital for angina) in people with type 2 diabetes.
For people living with obesity and metabolic syndrome, Ooi GJ et al (Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components. Int J Obes (Lond). 2017 Jun;41(6):902-908. doi: 10.1038/ijo.2017.59. Epub 2017 Mar 6. PMID: 28262677) reported that a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits, but that more weight loss was even better.
As well as metabolic improvements, >10% weight loss has also been shown to contribute to improvements in mechanical function eg. knee osteoarthritis (Huang MH, et al. The effects of weight reduction on the rehabilitation of patients with knee osteoarthritis and obesity. Arthritis Care Res. 2000 Dec;13(6):398-405. doi: 10.1002/1529-0131(200012)13:6<398::aid-art10>3.0.co;2-e. PMID: 14635316), mental health eg. health-related quality of life (Kolotkin RL et al. One-year health-related quality of life outcomes in weight loss trial participants: comparison of three measures. Health Qual Life Outcomes. 2009 Jun 9;7:53. doi: 10.1186/1477-7525-7-53. PMID: 19505338; PMCID: PMC2700089) and overall improved health eg. (Garvey WT et al. Endocr Pract 2016;22:1–20; 2. Look AHEAD Research Group. Lancet Diabetes Endocrinol 2016;4:913–21; 3. Lean ME et al. Lancet 2018;391:541–51; 4. Benraoune F and Litwin SE. Curr Opin Cardiol 2011;26:555–61; 5. Sundström J et al. Circulation 2017;135:1577–85).
Professor le Roux concluded his presentation by stating that >10% weight loss appears to be required to make a difference in cardiovascular events, but more weight loss is better for improving obesity associated complications, however more research is required to determine exactly how much weight loss leading to risk reduction in conditions such as cancer.
Long-term use of pharmacotherapy
Dr Josep Vidal (Hospital Clínic Barcelona, Spain) discussed the evidence for the safety and efficacy supporting the long-term use of pharmacotherapy for obesity. He began by outlining that there is a lack of long-term data to determine whether AOMs are safe and efficacious, thus far only orlistat (XENDOS study) has reported follow-up data out to four years, liraglutide three years, Phen/Topiramate two years, Naltrexone/Bupropion one year, and more recently, semaglutide and tirepatide, two years and one years, respectively.
Vidal defined efficacious as achieving WL>15% in at least 50% of patients, which he explained was not achieved by any of the 1st generation of AOMs, and although semaglutide and tirepatide have achieved this degree of WL at two and one years respectively, it is still to be determined if this will be maintained over the long term. Nevertheless, the outcomes from the STEP 1 trial demonstrated the impact on weight recurrence when participants stopped taking semaglutide.
To date, orlistat (XENDOS trial), liraglutide (SCALE re-diabetes study) and Phen/Topiramate (SEQUEL trial) reported no major safety concerns, although there was an increased incidence of gallbladder related events with liraglutide at three years. Two-year outcomes from the STEP 5 trial (semaglutide) showed an improvement of cardiovascular risk factors with no major safety concerns.
He concluded that the data from five RCT suggest that WL is maintained over time, with efficacy being larger with newer generation drugs, but discontinuation of the drugs is associated with weight regain. The data also indicates that WL is associated with improvement in cardiovascular risk factors and thus far, the ‘long-term’ use of current AOM’s does not appear to associate major safety concerns. However, more data is needed to confirm if the benefits of AOMs on cardiovascular risk factors and major events in the long-term as defined in the field of bariatric metabolic surgery (five-years and more).
Are there subgroups with special benefits from OMM treatment prior to surgery?
Next, Dr Nasreen Alfaris from King Fahad Medical Center in Riyadh, Saudi Arabia, reviewed the existing evidence regarding the routine use of OMM for preoperative weight loss and identified any subgroups that might benefit from OMM treatment prior to surgery. She highlighted that currently, there is insufficient level one data to routinely recommend OMM in the preoperative setting. However, she noted that the use of OMMs is supported by the potential to reduce perioperative risks and to increase the likelihood of patients achieving their weight loss targets and resolving comorbidities following Metabolic and Bariatric Surgery (MBS).
A study by Sun Y et al (Association of Preoperative Body Weight and Weight Loss With Risk of Death After Bariatric Surgery. JAMA Netw Open. 2020;3(5):e204803), examined the association of preoperative BMI and weight loss with 30-day mortality after bariatric surgery, and found the reduction in 30 day mortality before MBS if patients achieved 0%–5.0% weight loss was 24%, 5.0%–9.9% was 31% and 10.0%+ was 42%. Therefore, even moderate weight loss (ie, >0%-<5%) before MBS was associated with a lower risk of 30-day mortality.
Moreover, a study by Romero Funes D et al (Bariatric surgery decreases the number of future hospital admissions for diastolic heart failure in subjects with severe obesity: a retrospective analysis of the US National Inpatient Sample database. Surg Obes Relat Dis. 2022 Jan;18(1):1-8. doi: 10.1016/j.soard.2021.09.009. Epub 2021 Sep 16. PMID: 34756668) reported that compared to individuals who did not lose weight prior to surgery, those who lost 10% TBWL preoperatively had a 30% decreased odds of leak (OR 5.68%; 95% CI:0.56–0.84; p≤0.0001) and a 40% decrease in odds of mortality (OR 5 .60; 95% CI: 0.39– 0.92; p=0.02).
With regards to weight loss after MBS, pre-operative weight loss was not predictive of postoperative weight loss success after MBS and greater preoperative weight loss was associated with a mild decreased in length of stay but was not associated with a reduction in operative time, overall complication rates, ICU admissions or intraoperative complications, study by Samaan et al found (Preoperative weight loss as a predictor of bariatric surgery postoperative weight loss and complications." Journal of Gastrointestinal Surgery 26.1 (2022): 86-93). Furthermore, longer preoperative wait times do not result in improved weight loss or reduced adverse events and the determination of patient eligibility for bariatric surgery should rest with the health team and delay of treatment should be minimised (Eng V et al. Preoperative weight loss: is waiting longer before bariatric surgery more effective? Surg Obes Relat Dis. 2019 Jun;15(6):951-957. doi: 10.1016/j.soard.2019.03.012. Epub 2019 Mar 20. PMID: 31104959).
It should be noted that no high-quality data exist to support insurance-mandated preoperative weight loss (Kim JJ et al. ASMBS updated position statement on insurance mandated preoperative weight loss requirements. Surg Obes Relat Dis. 2016 Jun;12(5):955-9. doi: 10.1016/j.soard.2016.04.019. Epub 2016 Apr 22. PMID: 27523728), this practice is scientifically unfounded and discriminatory toward patients with obesity and the practice leads to attrition or delay in access to lifesaving treatment via MBS.
Indeed, the latest IFSO/ASMBS guidelines (Eisenberg D et al. 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) Indications for Metabolic and Bariatric Surgery. Obes Surg. 2023 Jan;33(1):3-14. doi: 10.1007/s11695-022-06332-1. Erratum in: Obes Surg. 2023 Jan;33(1):15-16. doi: 10.1007/s11695-022-06369-2. PMID: 36336720; PMCID: PMC9834364) state: “While there has been initial enthusiasm for weight loss prior to surgery, there are no data to support the practice of insurance-mandated preoperative weight loss; this practice is understood to be discriminatory, arbitrary, and scientifically unfounded, contributing to patient attrition, unnecessary delay of lifesaving treatment, and progression of life-threatening co-morbid conditions. A multidisciplinary team can help assess and manage the patient’s modifiable risk factors with a goal of reducing risk of perioperative complications and improving outcomes; the decision for surgical readiness should be primarily determined by the surgeon.”
OMM use
Orlistat – a study by Anderson JW et al (Orlistat for the management of overweight individuals and obesity: a review of potential for the 60-mg, over-the-counter dosage. Expert Opin Pharmacother. 2007 Aug;8(11):1733-42. doi: 10.1517/14656566.8.11.1733. PMID: 17685889), found orlistat modifies lifestyle behaviour, encourages lower fat-consumption and sets the stage for other healthy lifestyle changes. Although Lo HC et al (Effectiveness of a preoperative orlistat-based weight management plan and its impact on the results of one-anastomosis gastric bypass: A retrospective study. PLoS One. 2023 Jul 28;18(7):e0289006. doi: 10.1371/journal.pone.0289006. PMID: 37506080; PMCID: PMC10381073) concluded for patients taking orlistat there was no further weight loss was not observed at two years post-surgery.
Phentermine and phentermine/topiramate – Ard et al (Ard JD, Beavers DP, Hale E, Miller G, McNatt S, Fernandez A. Use of phentermine-topiramate extended release in combination with sleeve gastrectomy in patients with BMI 50 kg/m2 or more. Surg Obes Relat Dis. 2019 Jul;15(7):1039-1043. doi: 10.1016/j.soard.2019.04.017. Epub 2019 Apr 19. PMID: 31147285) reported phentermine/topiramate combined with LSG may help patients with a BMI >50 achieve greater weight loss and reach a BMI <40.
GLP-1ra - a study by Martines G et al (Efficacy of Intragastric Balloon versus Liraglutide as Bridge to Surgery in Super-Obese Patients. Obes Facts. 2023;16(5):457-464. doi: 10.1159/000531459. Epub 2023 Aug 14. PMID: 37579738; PMCID: PMC10601677) that compared intragastric balloon (IGB) to liraglutide before LSG, found IGB prior to LSG in super-obese patients could be considered an attractive alternative to liraglutide as bridging therapy before bariatric surgery. Nevertheless, Wilmington R et al (Liraglutide 3.0 mg (Saxenda) for Weight Loss and Remission of Pre-Diabetes. Real-World Clinical Evaluation of Effectiveness among Patients Awaiting Bariatric Surgery. Obes Surg. 2024 Jan;34(1):286-289. doi: 10.1007/s11695-023-06895-7. Epub 2023 Nov 28. PMID: 38012508; PMCID: PMC10781788) reported liraglutide 3.0 mg, with lifestyle management, reduced weight and improved glycaemic control with 92.3% and 72.2% achieved remission of pre-diabetes by six and 12 months, supporting liraglutide's application in certain high-risk populations, including patients waiting for bariatric surgical intervention. Furthermore, Rubio Herrera et al (Impact of Treatment with GLP1 Receptor Agonists, Liraglutide 3.0 mg and Semaglutide 1.0 mg, While on a Waiting List for Bariatric Surgery. Biomedicines. 2023 Oct 13;11(10):2785. doi: 10.3390/biomedicines11102785. PMID: 37893158; PMCID: PMC10604375.) reported losing >15% of initial weight after 52 weeks of treatment with liraglutide 3.0mg or semaglutide 1.0mg whilst on the waiting list for MBS, impacts patients' decisions regarding the final acceptance or rejection of the procedure.
She concluded future research is needed to explore the advantages of using AOMs especially with the advent of newer, more effective therapies, to assess their benefits and long-term outcomes when used for pre-operative weight loss, particularly as these newer OMM seem to result in >20% TBWL. However, the titration periods for newer therapies may last up to six months, which could result in the delay of surgery. Therefore, the question becomes pharmacotherapy vs. surgery rather than preoperative weight loss.
Body composition and nutritional Issues related to the use of OMM prior to MBS
In the next presentation, Dr Silvia Leite (University of Brasilia-DF, Brazil) discussed the effect of OMM on nutritional issues before MBS with respect to nutritional deficiencies (NDs), eating disorders (EDs) and body composition (fat and muscle mass).
She began by stating that OMMs can potentially cause NDs as they lead to a significant reduction in food intake like MBS. Therefore, vitamin & mineral supplementation with OMM should be considered; the literature supports that dietary consumption lower than 1200 Kcal per day does not achieve the adequate DRI for vitamins and minerals. Besides that, checking for nutritional deficiencies and correcting them before OMM/MBS is recommended as there is a high incidence of pre-surgery nutritional deficiencies, especially iron, folate, vitamin B12, and vitamin D.
Indeed, post-MBS, there is evidence that surgery may not change food preferences, so the quality of a patient’s diet may remain poor, and the same is likely true for OMM. She added that so far, studies of OMM do not routinely recommend multivitamin and mineral supplements and neither check for pre-existing deficiencies nor serum micronutrient levels during the studies or at the end. National guidelines (ASMBS, BOMSS etc) recommend assessing nutritional status before MBS and correcting deficiencies, so if one of the purposes of OMM before MBS is to help the person go forward for surgery, nutritional support needs to be considered.
Dr Leite recommended screening for EDs as decreased caloric intake has no effect on eating habits, masking EDs. Some studies have shown after MBS, patients eat smaller amounts of the same foods that they ate before surgery, with dietary energy density and relative macronutrient intake remaining constant. A simple and easy orientation can improve dietary intake. The focus should be on adequate protein intake with regular ingestion of fruits and vegetables.
The main concern regarding body composition is excessive muscle mass loss, and there is a lack of information about body composition in the pre-operative stage. Body composition evaluation via DXA, MRI, Bod Pod, CT and Bioelectrical impedance can highlight excessive muscle mass loss before MBS/OMM. All tools present their own biases, advantages, and limitations; knowing them and keeping a routine for body composition evaluation is a cornerstone for preventing muscle mass loss.
A decline in muscle mass function parameters, along with altered body composition, which means increased adipose tissue, could lead to a diagnosis of sarcopenic obesity in patients presenting with high BMI /weight circumference, based on ethnic cut -off points.. She explained that sarcopenic obesity is a vicious cycle of weight gain and muscle loss leading to reduced mobility, increased dependency and disability, risk of weight recurrence, risk of osteoporosis and frailty, comorbidities and mortality, especially in the older population.
Several OMM studies (1. Wilding et al., 2022 NEJM; 2. McCrimmon et al., 2020 Diabetolgia; 3. Heise et al. 2023 Diabetes Care, 4 Kushner, TOS meeting 2022) highlighted:
muscle mass loss equated to 38.9% of total weight loss (STEP 1: (Semaglutide): 140 patients DXA scans - n=951)
muscle mass loss equated to 39.6% of total weight loss (SUSTAIN 8 (Semaglutide): 178 patient DXA scans - n=882)
muscle mass loss equated to 14.3% of total weight loss (• SURMOUNT (Tirzapatide): 117 patient Bod pod - n=453)
muscle mass loss = 25% of total weight loss (SURMONT (Tirzapatide): 160 patient DXA scans - n=1604)
She noted that several guidelines and recommendations state that muscle mass loss can be prevented with adequate protein intake (at least 60g/day, 0.8g/Kg BW) and physical training for strength.
In conclusion, she said some degree of muscle mass loss occurs in most weight loss scenarios. Multivitamin and mineral supplements should be prescribed before the use of OMM, diet and eating habits should be evaluated before OMM, and muscle mass loss should be a concern. Therefore, adequate protein intake and physical activities may help.
Evidence to stop OMM before MBS
Next, Luca Busetto (University of Padova, Italy) started his presentation by making two statements; 1) OMMs should be paused before MBS to minimise the risk of aspiration and, 2) In general, pre-operative treatment with OAMs should be discontinued at the time of MBS. He subsequently presented evidence to support these statements.
The evidence of OMMs causing aspiration of gastric contents emerged in several case report papers, including ‘Pulmonary aspiration of gastric contents in two patients taking semaglutide for weight loss’ from Avraham SA et al (Anaesthesia Reports 2024;12:e12278). The mechanism by which glucagon-like peptide-1 (GLP-1) cause aspiration of gastric contents was explained by Baggio LL et a (Gastroenterology. 2007;132:2131). In their paper, they state “GLP-1 exerts glucoregulatory actions via slowing of gastric emptying and glucose-dependent inhibition of glucagon secretion.”
In June 2023, the American Society of Anesthesiologists, published its ‘Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists (Deepu S et al; ASA Consensus-based Guidance on Preoperative Management of Patients on Glucagon-like Peptide-1 Receptor Agonists. Anesthesiology 2024; 140:346–348 doi: https://doi.org/10.1097/ALN.0000000000004776), which stated:
In the days prior to the procedure:
For patients on daily dosing consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing consider holding GLP-1 agonists a week prior to the procedure/surgery.
This suggestion is irrespective of the indication (type 2 diabetes mellitus or weight loss), dose, or the type of procedure/surgery.
If GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycaemia.
Day of the procedure:
If gastrointestinal (GI) symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying elective procedure, and discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
If the patient has no GI symptoms, and the GLP-1 agonists have been held as advised, proceed as usual.
If the patient has no GI symptoms, but the GLP-1 agonists were not held as advised, proceed with ‘full stomach’ precautions or consider evaluating gastric volume by ultrasound, if possible and if proficient with the technique. If the stomach is empty, proceed as usual. If the stomach is full or if gastric ultrasound inconclusive or not possible, consider delaying the procedure or treat the patient as ‘full stomach’ and manage accordingly. Discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
There is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists.
Therefore, until we have adequate evidence, we suggest following the current ASA fasting guidelines.
Subsequently, in September 2023 Bloomgarden (Should glucagon-like peptide-1 receptor agonist treatment be withheld in preoperative management? J Diabetes. 2023 Sep;15(9):712-713. doi: 10.1111/1753-0407.13469. PMID: 37727016; PMCID: PMC10509509) asked whether these were reasonable recommendations: “There is extensive evidence that these agents are potent in lowering glycemia and indeed have glucose‐lowering benefit similar to that of basal insulin, without causing hypoglycaemia or weight gain…An even more worrisome consideration stems from the evidence of cardiovascular outcome benefits of GLP‐1RA seen over the long term; the question must be asked as to the safety of withholding these cardioprotective agents during the perioperative period, which is recognised to be associated with particularly high CVD risk. We must consider the injunction, primum non nocere, and recognize that by withholding a well‐tolerated treatment that is playing an important role in the management of a persons with diabetes we may actually create a ‘potential for harm’.”
Van Zuylen et al (Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration. Br J Anaesth. 2024 Apr;132(4):644-648. doi: 10.1016/j.bja.2024.01.001. Epub 2024 Jan 29. PMID: 38290907), confirmed that GLP-1 receptor agonists delay gastric emptying, “However, ongoing treatment attenuates this effect. The risk of aspiration during general anaesthesia is unknown. However, we advise caution in patients who recently commenced on GLP-1 receptor agonists. After over 12 weeks of treatment, standard fasting times likely suffice to manage the risk of pulmonary aspiration for most otherwise low-risk patients…” concluding that anaesthesiologists should “make a risk-benefit analysis concerning peri-operative measures.”
Finally, an analysis of a large database for administrative claims following surgery by Dixit AA et al (JAMA 2024 Apr 22: e245003) found no evidence that GLP-1s complicates the surgical pathway.
To access Module II, please click here
To access Module III, please click here
A review and outcomes of the Consensus Meeting in Vienna will be presented at the following session in Melbourne: Session 2.2.2 - Consensus meeting in Vienna: The use of Obesity Management Medications in the context of MBS, on Thursday 5 September from 1.30pm – 3pm.
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