Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial.

Importance: Metabolic surgery leads to weight loss and improved health, but these outcomes are highly variable. Poor weight loss is associated with lower circulating levels of glucagon-like peptide-1 (GLP-1). Objective: To assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. Design, Setting, and Participants: The Evaluation of Liraglutide 3.0 mg in Patients With Poor Weight Loss and a Suboptimal Glucagon-Like Peptide-1 Response (BARI-OPTIMISE) randomized placebo-controlled trial recruited adult patients at least 1 year after metabolic surgery who had experienced 20% or less body weight loss from the day of surgery and a suboptimal nutrient-stimulated GLP-1 response from 2 hospitals in London, United Kingdom, between October 2018 and November 2019. Key exclusion criteria were type 1 diabetes; severe concomitant psychiatric, gastrointestinal, cardiac, kidney or metabolic disease; and use of insulin, GLP-1 receptor analogues, and medication that can affect weight. The study period was 24 weeks followed by a 4-week follow-up period. Last participant follow-up was completed in June 2020. All participants and clinical study personnel were blinded to treatment allocation. Of 154 assessed for eligibility, 70 met trial criteria and were included in the study, and 57 completed follow-up. Interventions: Liraglutide, 3.0 mg, once daily or placebo as an adjunct to lifestyle intervention with a 500-kcal daily energy deficit for 24 weeks, on a 1:1 allocation by computer-generated randomization sequence, stratified by surgery type (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) and type 2 diabetes status. Main Outcome and Measures: The primary outcome was change in percentage body weight from baseline to the end of the 24-week study period based on an intention-to-treat analysis. Participant safety was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events. Results: A total of 70 participants (mean [SD] age, 47.6 [10.7] years; 52 [74%] female) with a poor weight loss response following RYGB or SG were randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). All participants received at least 1 dose of the trial drug. Eight participants discontinued treatment (4 per group), and 2 in the 3.0-mg liraglutide group and 1 in the placebo group were lost to follow-up. Due to COVID-19 restrictions, 3 participants in the 3.0-mg liraglutide group and 7 in the placebo group were unable to attend their final in-person assessment. Estimated change in mean (SD) percentage body weight from baseline to week 24 was -8.82 (4.94) with liraglutide, 3.0 mg (n = 31), vs -0.54 (3.32) with placebo (n = 26). The mean difference in percentage body weight change for liraglutide, 3.0 mg, vs placebo was -8.03 (95% CI, -10.39 to -5.66; P < .001). Adverse events, predominantly gastrointestinal, were more frequent with liraglutide, 3.0 mg (28 events [80%]), than placebo (20 events [57%]). There were no serious adverse events and no treatment-related deaths. Conclusion and Relevance: These findings support the use of adjuvant liraglutide, 3.0 mg, for weight management in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03341429.

Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes.

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P < 1 × 10-7). We connect obesity-associated methylation variations to transcriptomic changes at >500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

Impact of sleeve gastrectomy compared to Roux-en-y gastric bypass upon hedonic hunger and the relationship to post-operative weight loss.

'Hedonic hunger' indicates the desire to consume food in the absence of an energy requirement. Hedonic hunger can be investigated using the validated Power of Food Scale (PFS). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are currently the most effective treatment options for severe obesity. Following RYGB, hedonic hunger diminishes, which may contribute to sustained weight loss. There are no data examining the effect of SG on hedonic hunger. We prospectively evaluated hedonic hunger using PFS in patients with severe obesity prior to and 6 months after SG (n = 95) or RYGB (n = 44) and investigated the procedure-specific relationship between percentage weight loss (%WL) and hedonic hunger. Anthropometric data were collected at baseline after 6 months, 12 months and 24 months post-operatively. PFS contains 15 items grouped into 3 domains considering when food is: available (FA), present (FP), tasted (FT) and a total score (TS). At 6 months, a significant reduction was seen in all categories post-SG (p < 0.0001) and in TS (p = 0.003), FA (p = 0.0006) and FP (p = 0.0007) post-RYGB. A significantly larger reduction in FP scores was seen post-SG (p = 0.01). Post-SG, a significant correlation with 6-month %WL was noted for changes in FP (p = 0.03) and TS (p = 0.03). Post-SG changes in FP and TS predicted 24-month %WL. Post-RYGB significant correlations were seen between 6-month %WL and dFA (p = 0.04) and dFP (p = 0.03). Changes in FA, FP and TS were predictive of 12-month %WL. HH is reduced following both SG and RYGB with a greater reduction following SG and is related to post-operative %WL. PFS may have a role as a predictive tool for post-operative outcomes following SG and RYGB.

Internal Hernia After Laparoscopic One-Anastomosis (Mini) Gastric Bypass: Video Case Series of a Single-Center Experience.

Internal hernia (IH) after one-anastomosis gastric bypass (OAGB) was thought to have an extremely low incidence. In this video, we report three cases of post-OAGB symptomatic internal herniation. The first case is a 45-year-old female who presented 4 months after her OAGB with crampy abdominal pain and reflux symptoms. An exploratory laparoscopy showed Petersen's hernia; the hernia was reduced with no ischemia and the defect was closed. The second case is a 40-year-old male who presented 7 months after his surgery with abdominal pain and reflux. An exploratory laparoscopy showed Petersen's hernia; bowel was reduced and defect was closed through a laparotomy. The third case is a 64-year-old male who presented with refractory biliary reflux after OAGB. An elective diagnostic laparoscopy showed Petersen's hernia; the hernia was reduced and defect was closed. All patients recovered well with no recurrence of symptoms on follow-up. Internal hernia after OAGB is more common than the reported incidence. The threshold for diagnostic laparoscopy should be lowered for a OAGB patient with symptoms suggestive of IH.

Is Pre-operation Social Connectedness Associated with Weight Loss up to 2 Years Post Bariatric Surgery?

BACKGROUND: To date, little attention has been paid to supportive relationships as factors contributing to weight loss from bariatric surgery. MATERIAL AND METHODS: This prospective study examined whether total percentage weight loss (%TWL) at 3, 12 and 24 months post-surgery varies by distinct aspects of pre-surgery social support (received emotional and practical support and contact with friends and family) in a sample of bariatric surgery candidates (n = 182). These associations were tested with linear regression models adjusted for gender, age, ethnicity, employment status, self-esteem, mastery and time elapsed since the day of surgery. RESULTS: One hundred fifty-four participants underwent a bariatric procedure, and all but seven provided weight loss data at least at one occasion. Emotional support and contact with friends were positively associated with %TWL at 3, 12 and 24 months, and the magnitude of these associations was large. For instance, in the fully adjusted models, %TWL at 24 months increased by 2.36% (SE 1.17, p = 0.048) with each increase of one standard deviation in emotional support and was higher by 9.23% (SE 4.31, p = 0.035) for participants who reported seeing 1-5 friends per month compared with those who saw none. There was some evidence for a positive association between practical support and %TWL at 3 and 12 months post-surgery. CONCLUSION: Supportive relationships are important contributors to weight loss from bariatric surgery. If replicated in future studies, these findings could inform clinical care and interventions aimed at improving support systems of bariatric surgery candidates.

Early Effect of Bariatric Surgery on Urogenital Function in Morbidly Obese Men.

INTRODUCTION: Obesity is an independent risk factor for erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Bariatric surgery has been shown to improve erectile function and urinary symptoms in medium- to long-term studies (3- to 12-month postoperative follow-up). AIM: To investigate the early effect (1 month postoperatively) of bariatric surgery on ED and LUTS, which has not previously been investigated. METHODS: Morbidly obese men (body mass index > 35 kg/m2) undergoing bariatric surgery were asked to complete the International Index of Erectile Function (IIEF) and International Prostate Symptom Score (IPSS) questionnaires before surgery and 1, 3, and 6 months after surgery. MAIN OUTCOME MEASURE: The influence of bariatric surgery on urogenital function, body mass index, fasting blood glucose, and glycated hemoglobin were analyzed using parametric and non-parametric tests for paired samples. RESULTS: Of 30 patients who completed the study, 18 reported ED (IIEF score < 25) and 14 reported moderate or severe LUTS (IPSS ≥ 8) before the operation. Twelve patients had ED and moderate or severe LUTS. IIEF score, IPSS, body mass index, percentage of weight loss, fasting blood glucose, and glycated hemoglobin showed significant and rapid improvement after bariatric surgery starting at the 1-month postoperative time point and improvement continued throughout the study in all patients with ED or moderate to severe LUTS. CONCLUSION: This is the first study showing improvement in erectile and urinary function within 1 month after bariatric surgery, an effect that was parallel to glycemic improvement and weight loss.

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10-7, range P = 9.2 × 10-8 to 6.0 × 10-46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10-6, range P = 5.5 × 10-6 to 6.1 × 10-35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

Current Status of Preoperative Oesophago-Gastro-Duodenoscopy (OGD) in Bariatric NHS Units-a BOMSS Survey.

PURPOSE: Preoperative oesophago-gastro-duodenoscopy (p-OGD) is often routinely employed in patients undergoing bariatric surgery. The value of p-OGD is still unclear; however, since all bariatric procedures modify stomach anatomy differently with exclusion of the remnant in a majority of cases, the question arises whether there is a rational for including it routinely in the preoperative pathway. MATERIAL AND METHODS: To assess the current status of p-OGD in the UK, a survey was sent to the British Obesity & Metabolic Surgery Society members, regarding preoperative evaluation of patients, focusing on the role of p-OGD. Forty-nine UK bariatric units (in excess of 5000 patients estimated caseload/year) answered. RESULTS: The survey has shown that 44 units (90 %) include OGD in their preoperative work up, routinely or selectively. According to results, 25 units (51 %) changed the operative plans after OGD because of peptic ulcer (46 %), hiatus hernia (43 %), Barrett's oesophagus (32 %) or gastrointestinal stromal tumour (25 %). Only 2 units (7 %) found incidental gastrointestinal cancer. When specifically asked, p-OGD was believed to be essential in patients with family history of gastrointestinal cancer (61 %), pernicious anaemia (57 %) and reflux symptoms (54 %). Five units (10 %) considered p-OGD completely unnecessary. Only 11 units (25 %) would not be able to accommodate routine p-OGD in all patients. CONCLUSIONS: Most units value p-OGD, either selectively or routinely, in preparation for bariatric surgery. However, there seems to be a discrepancy on the specific risk factors involved in the selection process. National and international guidelines are advocated.

Reported appetite, taste and smell changes following Roux-en-Y gastric bypass and sleeve gastrectomy: Effect of gender, type 2 diabetes and relationship to post-operative weight loss.

Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments.

Gastro-cutaneous fistula 4 years after a fully resolved staple line leak in sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG) has become a mainstream procedure in the management of obesity. Staple line leak is a challenging complication. We report a unique case of successfully treated leak after sleeve gastrectomy, presented ex novo 4 years later as a gastro-cutaneous fistula (GCF). Nothing similar was found in the literature. A 31-year-old woman underwent an LSG, complicated by an early type I leak treated successfully. After 4 years of clinical remission, the leak presented as a GCF. The conservative approach failed and a laparoscopic fistulectomy was first attempted, but after recurrence a completion gastrectomy was performed. A staple line leak is one of the most important complications after sleeve gastrectomy. Once chronic it evolves into GCF, the treatment of which is challenging. Given the absence of guidelines, experience is fundamental in its management. In our case, eventually a total gastrectomy was required.

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy.

UNLABELLED: Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m(2)). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m(2), weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m(2)), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m(2) after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting. LEARNING POINTS: Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss follows a normal distribution with extremes of 'good' and 'poor' response.Profound anorexia and excessive weight loss post-SG may be associated with markedly elevated circulating fasted PYY and post-meal PYY and GLP1 levels.Octreotide treatment can produce symptomatic relief and weight regain for post-SG patients that have an extreme anorectic and weight loss response.The present case highlights the value of measuring circulating gut hormone levels in patients with post-operative anorexia and extreme weight loss.

Early postoperative weight loss predicts maximal weight loss after sleeve gastrectomy and Roux-en-Y gastric bypass.

BACKGROUND: Previous studies show that 'poor responders' to Roux-en-Y gastric bypass (RYGBP) may be identified on the basis of early postoperative weight loss. Early identification of poor responders could allow earlier provision of postoperative behavioural and/or intensive lifestyle interventions and enhance their maximal weight loss. Our aim was to investigate whether early postoperative weight loss predicts the maximal weight loss response after RYGBP and sleeve gastrectomy (SG). METHODS: We undertook a retrospective cross-sectional study of 1,456 adults who underwent either RYGBP (n = 918) or SG (n = 538) as a primary procedure in one of two European centres. Postoperative weight loss was expressed as weight loss velocity (WLV) and percentage weight loss. Linear regression analyses were performed to determine the association of early postoperative weight loss with maximal %WL, including adjustment for baseline variables. RESULTS: There was marked variability in maximal %WL following both RYGBP (mean 32.9 %, range 4.1-60.9 %) and SG (mean 26.2 %, range 1.1-58.3 %). WLV 3-6 months postoperatively was more strongly associated with maximal %WL (r (2) = 0.32 for RYGBP and r (2) = 0.26 for SG, P < 0.001 for both) than either WLV 0-6 weeks or 6 weeks to 3 months postoperatively (r (2) = 0.14 and 0.10 for RYGBP, respectively; r (2) = 0.18 and 0.21 for SG, respectively; P < 0.001 for all). Multiple linear regression analysis, including baseline variables of age, sex, preoperative BMI, type 2 diabetes, ethnicity, and bariatric centre, revealed that 3-6 month WLV was an independent predictor of maximal %WL in both SG and RYGBP groups (standardised ß-coefficients 0.51 and 0.52, respectively; P < 0.001 for both). CONCLUSIONS: There is a marked variability in weight loss response following RYGBP and SG. Early postoperative weight loss can be used to identify patients whose predicted weight loss trajectories are suboptimal. Early targeting of poor responders with more intensive postoperative lifestyle and behavioural support could potentially enhance their weight loss response.

Timing of pregnancy in obese women after bariatric surgery.

AIMS: There is an increased risk of preterm and small-for-gestational-age births associated with bariatric surgery, especially if maternal early pregnancy body mass index (BMI) is <30.0kg/m(2). However, the relationship between timing of pregnancy post-bariatric surgery and effects on pregnancy outcome are unknown. The aim of this study was to investigate the timing of pregnancy post-bariatric surgery and compare early pregnancy BMI between women who became pregnant before or after the recommended 12month postoperative window. METHODS/RESULTS: Women who underwent either sleeve gastrectomy or gastric bypass and subsequently became pregnant were offered antenatal care in a multidisciplinary high-risk clinic. There were 50 such pregnancies in women who attended our high-risk clinic (n=26 <12months and n=24 >12months postoperatively, mean estimated times to conception 31.9±12.6weeks and 102.8±37.7weeks respectively). There was no significant difference in early pregnancy BMI between groups (33.2±6.8kg/m(2) and 32.5+2.1kg/m(2) respectively, p=0.78). There were 6 miscarriages in each group, however more women in the <12month (n=8) than in the >12months group (n=2) were lost-to-follow-up (likelihood ratio 4.2, p=0.04). CONCLUSIONS: Women who became pregnant <12months post-bariatric surgery were, for unknown reasons, less likely to attend follow-up in a specialist antenatal clinic than those who became pregnant >12months postoperatively. Further research is required to explore the relationship between timing of pregnancy post-bariatric surgery and pregnancy outcome and to identify predictors more clinically useful than early pregnancy BMI, in this high-risk pregnancy group.

Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans.

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) reduces appetite and induces significant and sustainable weight loss. Circulating gut hormones changes engendered by LRYGBP are implicated in mediating these beneficial effects. Laparoscopic sleeve gastrectomy (LSG) is advocated as an alternative to LRYGBP, with comparable short-term weight loss and metabolic outcomes. LRYGBP and LSG are anatomically distinct procedures causing differential entero-endocrine cell nutrient exposure and thus potentially different gut hormone changes. Studies reporting the comparative effects of LRYGBP and LSG on appetite and circulating gut hormones are controversial, with no data to date on the effects of LSG on circulating peptide YY3-36 (PYY3-36) levels, the specific PYY anorectic isoform. In this study, we prospectively investigated appetite and gut hormone changes in response to LRYGBP and LSG in adiposity-matched non-diabetic patients. Anthropometric indices, leptin, fasted and nutrient-stimulated acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), PYY3-36 levels and appetite were determined pre-operatively and at 6 and 12 weeks post-operatively in obese, non-diabetic females, with ten undergoing LRYGBP and eight adiposity-matched females undergoing LSG. LRYGBP and LSG comparably reduced adiposity. LSG decreased fasting and post-prandial plasma acyl-ghrelin compared to pre-surgery and to LRYGBP. Nutrient-stimulated PYY3-36 and active GLP-1 concentrations increased post-operatively in both groups. However, LRYGBP induced greater, more sustained PYY3-36 and active GLP-1 increments compared to LSG. LRYGBP suppressed fasting hunger compared to LSG. A similar increase in post-prandial fullness was observed post-surgery following both procedures. LRYGBP and LSG produced comparable enhanced satiety and weight loss. However, LSG and LRYGBP differentially altered gut hormone profiles.

Age- and sex-specific effects on weight loss outcomes in a comparison of sleeve gastrectomy and Roux-en-Y gastric bypass: a retrospective cohort study.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) are the most common bariatric procedures undertaken globally but there are no evidenced-based criteria that inform the selection of one operation over the other. The purpose of this study was thus to compare weight loss outcomes between RYGBP and SG, and to define patient factors affecting weight loss. METHODS: A single-centre two-year follow-up retrospective cohort study of all adults who underwent either RYGBP (n = 422) or SG (n = 432) between 2007 and 2012, at University College London Hospitals National Health Service Foundation Trust, an academic tertiary referral centre, was undertaken. Multilevel linear regression was used to compare weight loss between groups, enabling adjustment for preoperative BMI (body mass index) and evaluation for interaction factors. RESULTS: One- and two-year results showed that unadjusted BMI loss was similar between groups; 13.7 kg/m(2) (95% CI: 12.9, 14.6 kg/m(2)) and 12.8 kg/m(2) (95% CI: 11.8, 13.9 kg/m(2)) for RYGBP patients respectively compared with 13.3 kg/m(2) (95% CI: 12.0, 14.6 kg/m(2)) and 11.5 kg/m(2) (95% CI: 10.1, 13.0 kg/m(2)) for SG patients respectively. Adjusting for preoperative BMI, there was 2.2 kg/m(2) (95% CI: 1.5, 2.8) and 2.3 kg/m(2) (95% CI: 1.3, 3.3) greater BMI loss in the RYGBP group compared to the SG group at one and two years respectively (P < 0.001 for both). The interaction analyses demonstrated that age and sex had important differential impacts on SG and RYGBP weight outcomes. Men under 40 and women over 50 years obtained on average far less benefit from SG compared to RYGBP, whereas men over 40 years and women under 50 years experienced similar weight loss with either procedure (P = 0.001 and 0.022 for interaction effects at one and two years respectively). CONCLUSIONS: Our results show that patient sex and age significantly impact on weight loss in a procedure-dependent manner and should be considered when choosing between RYGBP and SG. Optimizing procedure selection could enhance the effectiveness of bariatric surgery, thus further increasing the benefit-to-risk ratio of this highly effective intervention.