Roux-en-Y gastric bypass, adjustable gastric banding, or sleeve gastrectomy for severe obesity (By-Band-Sleeve): a multicentre, open label, three-group, randomised controlled trial (Шлункове шунтування за RY (Roux-en-Y), регульоване шлункове бандажування або рукавна резекція шлунка при тяжкому ожирінні (By-Band-Sleeve): багатоцентрове, відкрите, трьохгрупове, рандомізоване контрольоване дослідження»)

Summary

Background

The health risks of severe obesity can be reduced with metabolic and bariatric surgery, but it is uncertain which operation is most effective or cost-effective. We aimed to compare Roux-en-Y gastric bypass, adjustable gastric banding, and sleeve gastrectomy in patients with severe obesity.

Methods

By-Band-Sleeve is a pragmatic, multi-centre, open-label, randomised controlled trial conducted in 12 hospitals in the UK. Eligible participants were adults (aged ≥18 years) meeting national criteria for metabolic and bariatric surgery. Initially, a 2-group trial (Roux-en-Y gastric bypass versus adjustable gastric banding) became a 3-group trial to include sleeve gastrectomy at 2·6 years from study opening, when it became widely used in the UK. Co-primary endpoints were weight (proportion achieving ≥50% excess weight loss) and quality-of-life (EQ-5D utility score) at 3 years. If the proportion achieving at least 50% excess weight loss was non-inferior (<12% difference between groups) and quality-of-life was superior, sleeve gastrectomy and Roux-en-Y gastric bypass were considered more effective than adjustable gastric banding, and sleeve gastrectomy more effective than Roux-en-Y gastric bypass. Cost-effectiveness of the procedures was compared. This trial is registered with ClinicalTrials.gov, NCT02841527, and ISRCTN, 00786323.

Results

Between Jan 16, 2013, and Sept 27, 2019, 1351 participants were randomly assigned; five withdrew consent and 1346 (mean age 47·3 [SD 10·6] years, 1020 [76%] women, 324 (24%) men, and two with missing data, mean weight of 129·7 kg [23·6] and mean BMI of 46·4 [6·9] kg/m2) were included in this report. Of 1346 participants, 462 (34%) were in the Roux-en-Y gastric bypass group, 464 (34%) in the adjustable gastric banding group, and 420 (31%) in the sleeve gastrectomy group. 1183 (88%) participants underwent surgery. 276 (68%) of 405 participants in the Roux-en-Y gastric bypass group, 97 (25%) of 383 participants in the adjustable gastric banding group and 141 (41%) of 342 participants in the sleeve gastrectomy group achieved at least 50% excess weight loss (adjusted risk difference: Roux-en-Y gastric bypass vs adjustable gastric banding 41% [98% CI 34 to 48]; sleeve gastrectomy vs adjustable gastric banding 15% [5 to 24]; sleeve gastrectomy vs Roux-en-Y gastric bypass, –26% [–36 to –16%]). Mean EQ-5D scores were 0·72 for Roux-en-Y gastric bypass, 0·62 for adjustable gastric banding, and 0·68 for sleeve gastrectomy (adjusted mean difference: Roux-en-Y gastric bypass vs adjustable gastric banding 0·08 [0·04 to 0·12], sleeve gastrectomy vs adjustable gastric banding 0·05 [0·01 to 0·09], and sleeve gastrectomy vs Roux-en-Y gastric bypass –0·03 [–0·07 to 0·01]). 1651 adverse events were reported following surgery (5·7 per year after sleeve gastrectomy, 6·0 per year after Roux-en-Y gastric bypass, and 4·6 per year after adjustable gastric banding). There were 11 deaths from randomisation to 3 years: one attributable to surgery (in the adjustable gastric bypass group, during the surgical admission) and ten not attributable to surgery (four each in the Roux-en-Y gastric bypass and adjustable gastric banding groups and two in the sleeve gastrectomy group). Roux-en-Y gastric bypass was most cost-effective.

Interpretation

Roux-en-Y gastric bypass and sleeve gastrectomy are more effective than adjustable gastric banding. Sleeve gastrectomy has inferior weight loss and lower mean quality of life score compared with Roux-en-Y gastric bypass. Based on this evidence, it is recommended that patients electing to have metabolic and bariatric surgery are advised to have Roux-en-Y gastric bypass. Where contraindicated or unfeasible, sleeve gastrectomy should be offered. This evidence does not support adjustable gastric band as standard treatment for severe obesity.

Funding

National Institute for Health and Care Research Health Technology Assessment Programme.

Research in context

Evidence before this study

Metabolic bariatric surgery is a well established intervention for people living with severe obesity, yet the optimal surgical procedure remains uncertain. Before 2012, Roux-en-Y gastric bypass and adjustable gastric banding were the most commonly performed procedures; by 2015, this had changed to Roux-en-Y gastric bypass and sleeve gastrectomy. However, the comparative evidence for all procedures was limited and less was known about the impact of different types of metabolic and bariatric surgery on quality-of-life. Reviews highlighted that trials would be difficult to conduct because preferences might prohibit randomisation.

Added value of this study

The By-Band-Sleeve study randomised 1351 participants with support of a recruitment intervention. 88% of participants underwent surgery. At 3 years follow-up, Roux-en-Y gastric bypass and sleeve gastrectomy were more effective than adjustable gastric banding, with non-inferior weight loss and superior quality-of life. Weight loss following sleeve gastrectomy was inferior to Roux-en-Y gastric bypass. Quality-of-life differences between sleeve gastrectomy and Roux-en-Y gastric bypass were not significant, but favoured Roux-en-Y gastric bypass. Fewer adverse events occurred after sleeve gastrectomy compared with Roux-en-Y gastric bypass and adjustable gastric banding but Roux-en-Y gastric bypass was found to be the most cost-effective and to provide value for money for the National Health Service. Subgroup analyses by diabetes status and weight at baseline supported the findings of the primary analyses.
Implications for all the available evidence
Roux-en-Y gastric bypass and sleeve gastrectomy are more effective than adjustable gastric banding for weight loss, quality-of-life, and reduction in comorbidities at 3 years follow-up. Sleeve gastrectomy is inferior to Roux-en-Y gastric bypass for weight loss with lower but statistically similar quality of life. Trials comparing Roux-en-Y gastric bypass with obesity management medications will inform the management of the severe obesity as the prevalence continues to rise.

Introduction

Global rates of obesity (defined as a BMI ≥30 kg/m2)1 and severe obesity (defined as a BMI ≥35 kg/m2), are increasing, with over 25% of the world’s population predicted to be affected by 2035.2 As an elevated BMI is strongly associated with multiple diseases, effective preventative and treatment interventions are important. Lifestyle interventions form the basis of obesity management but if these prove ineffective, metabolic and bariatric surgery or obesity medications might be offered. Metabolic and bariatric surgery can lead to 20–30% total weight loss. Trials show that obesity management medications can lead to reductions of up to 24% total weight loss, although it could be less in real-world settings, and longer-term outcomes and tolerability of these drugs are uncertain.1,3–6 Although metabolic and bariatric surger is widely undertaken in some countries (>600 000 primary procedures were performed worldwide in 2018), it can be associated with morbidity and there is controversy about which procedure is most clinically effective and cost-effective.7 In the UK, Roux-en-Y gastric bypass and adjustable gastric banding predominated until 2015 despite scarce comparative effectiveness data. Only two small randomised controlled trials (RCTs) compared Roux-en-Y gastric bypass with adjustable gastric banding.8,9 This context informed the conception of the By-Band study in 2011, which aimed to compare the clinical effectiveness, cost-effectiveness, and safety of Roux-en-Y gastric bypass and adjustable gastric banding. The By-Band study opened in 2012 with the option to consider adding sleeve gastrectomy as a third group. By 2014, sleeve gastrectomy was increasingly used in the UK and internationally, based on safety and short-term outcome data.10 At the same time, adjustable gastric banding practice declined because of a perceived lack of effectiveness and the need for re-operation.7 In view of this changing practice, with support of the funder and study oversight groups, sleeve gastrectomy was added to By-Band study in 2015. The By-Band-Sleeve trial aimed to compare the clinical effectiveness, cost-effectiveness, and safety of Roux-en-Y gastric bypass, adjustable gastric banding, and sleeve gastrectomy in patients with severe obesity 3 years after randomisation.

Methods

Study design and participants
The design and rationale for the addition of a third group and characteristics of the By-Band-Sleeve study participants have been described previously and are summarised in the appendix (p 5)·11–13 In brief, the study began as a two-group trial of Roux-en-Y gastric bypass versus adjustable gastric banding. A third group (sleeve gastrectomy) was added after 32 months of recruitment because of changing national and international practice and accumulating data about the safety of sleeve gastrectomy. By-Band-Sleeve study is a pragmatic, multi-centre, open-label, RCT conducted in 12 hospitals in the UK. Adults referred for first-time metabolic and bariatric surgery who met the National Institute for Health and Care Excellence (NICE) guidelines were eligible to participate. Approval was obtained from the Southwest-Frenchay Research Ethics Committee (reference 11/SW/0248) on Dec 6, 2011. All participants gave written informed consent. The trial is registered (ISRCTN No: 00786323, ClinicalTrials.gov NCT02841527).

Randomisation and blinding

Randomisation took place after baseline assessments had been completed. Participants were initially randomised 1:1 to Roux-en-Y gastric bypass or adjustable gastric banding in six centres. After addition of sleeve gastrectomy, participants were randomised into one of the three groups in 12 sites, varying the allocation ratio by centre to achieve approximate balance in the numbers per group at complete recruitment. Treatment assignments were stratified by centre. Cohort minimisation (with a random element) was used to ensure balance across groups by diabetes status and baseline BMI (appendix p 6). Randomisation was via a secure internet-based system provided by Sealed Envelope (Sealed Envelope, London, UK). Clinicians, research staff, and participants were made aware of the group assignment. Recruitment was supported throughout by a QuinteT Recruitment Intervention that involved interviews with patients, surgeons, and research staff, audio recording of recruitment consultations, analyses of recruitment data and review or revision of patient information. Data were used to support recruiters to explain clinical equipoise and address preferences.14

Procedures

Preoperative evaluation included routine workup, laboratory blood analyses, anthropometric measures, and completion of quality-of-life questionnaires before randomisation. Preoperative endoscopy was performed if clinically indicated. All participants were prescribed a low-calorie diet for 2–4 weeks preoperatively. Thromboprophylaxis and pre-operative antibiotics were administered according to national guidelines.

Participating centres were mandated to have a specialist multidisciplinary bariatric team, to perform a minimum of 50 bariatric operations annually and to have a minimum of two surgeons involved in the By-Band-Sleeve trial. Individual surgeons had to have performed at least 50 adjustable gastric banding, 100 Roux-en-Y gastric bypass, and 50 sleeve gastrectomy procedures, be willing to offer participation in the trial to patients, and carry out the surgery according to the randomised allocation and pre-agreed surgical protocols.

Compliance with the allocated surgery was monitored.15 A crossover occurred when a participant was allocated one surgery but received another as their primary bariatric surgical procedure. Adherence to the pre-agreed surgical protocols that included mandated, prohibited, and flexible components was recorded. All procedures were to be performed laparoscopically. Roux-en-Y gastric bypass included construction of a small gastric pouch according to the surgeon’s usual practice, except that a horizontal gastric pouch that included fundus was prohibited. The creation of gastrojejunostomy and jejunojejunostomy was at the surgeon’s discretion, although upper limits of 75 cm and 150 cm were recommended for the biliary and gastric limbs respectively. The route of the Roux limb (antecolic or retrocolic) was according to surgeon choice. Closure of iatrogenic mesenteric defects was mandatory from April, 2018, onwards. Using a bougie for the gastric pouch was optional. The type and size of adjustable gastric band used was at the surgeon’s discretion. It was mandatory to (1) dissect the lesser curve using the pars flaccida technique; (2) fix the adjustable gastric band gastro-gastric tunnelling sutures (any fixation method allowed), and (3) fix the adjustment port to the anterior abdominal wall. Sleeve gastrectomy was done by vertical stapled resection of the stomach along the greater curvature, using a bougie up to 40Fr for calibration. Use of additional sutures, clips, reinforcement of the staple line, and its testing was according to surgeon choice. Undertaking a hiatal hernia repair and cholecystectomy were at the surgeon’s discretion. Surgical equipment (eg, type and length of staplers) used was recorded.

Outcomes

After discharge participants attended hospital for surgical or dietetic, or both, follow-up except during the COVID-19 pandemic, which necessitated telephone appointments. Research appointments were designed to coincide with standard NHS care at 4 weeks post-surgery and month 6, 12, and 24 after randomisation, with one additional follow-up at 3 years after randomisation. Follow-up consultations for participants with an adjustable gastric banding in the first 24 postsurgical months were undertaken according to participant need. Postoperative vitamin and mineral supplementation were prescribed in accordance with national guidelines.

The co-primary outcomes were (1) loss of greater than or equal to 50% excess weight (defined as 100 × [BMI at 3 years – BMI at randomisation]/[BMI at randomisation – 25], and (2) the EQ-5D-5L utility score at 3 years after randomisation. Secondary outcomes included percentage total weight loss and BMI, disease-specific and other generic quality-of-life measures (Short-Form 12 (SF-12), Impact of Weight on Quality of life [IWQOL-Lite], Gastro-intestinal Quality of Life Index [GIQLI], Hospital and Anxiety Depression Scale [HADs]), dietary intake (assessed by interview), and binge eating behaviour (assessed via questionnaire),13 sleepiness (Epworth sleepiness scale), and resource use.14 Blood measurements were used to assess metabolic control (HbA1c, fasting glucose, triglycerides, total cholesterol and HDL-cholesterol, plus blood pressure); safety (haemoglobin, 25-hydroxyvitamin D, calcium, ferritin, folate, parathyroid hormone, serum iron, and vitamin B12); and liver and kidney function (alkaline phosphatase, alanine transaminase, and creatinine). Liver fibrosis was assessed using the ELF test measured at baseline and 3 years.
Adverse health events from randomisation to 3 years were captured and coded using the Medical Dictionary for Regulatory Activities (MedDRA; appendix p 8). Events meeting the regulatory definition of a serious adverse event were identified. Reported abdominal operations and overnight admissions were coded with clinical input. Hospital attendances for abdominal pain were recorded as unexpected serious adverse events.

Statistical analyses

We hypothesised that Roux-en-Y gastric bypass and sleeve gastrectomy would have non-inferior weight loss and superior quality-of-life to adjustable gastric banding, and that sleeve gastrectomy would have non-inferior weight loss and superior quality-of-life to Roux-en-Y gastric bypass. Both hypotheses had to be supported to conclude that Roux-en-Y gastric bypass or sleeve gastrectomy is more effective than adjustable gastric banding, or that sleeve gastrectomy is more effective than Roux-en-Y gastric bypass. The expected proportion of participants achieving at least 50% excess weight loss at 3 years was 70% (based on registry data). The non-inferiority margin (12%) was chosen by clinicians and patient representatives. The target standardised difference for the EQ-5D-5L was 0·2, with correlations between before and after randomisation measures and repeated after randomisation measures of 0·5 and 0·75, respectively. The sample size of 447 per group was sufficient to test the two hypotheses with 90% power and 1% (one-sided) statistical significance for the non-inferiority hypothesis and 2% (two-sided) statistical significance for the superiority hypothesis, (chosen because there are three comparisons), allowing for 15% loss to follow-up (see appendix p 6).

The statistical analysis plan was finalised before data lock (March 7, 2023) and any analyses were performed. Outcomes were compared on an intention-to-treat (ITT) basis, except where indicated. The ITT, per-protocol, and safety populations are defined in the appendix (pp 8–9). Analyses were adjusted by diabetes status and BMI at baseline and baseline values of the outcome where available fitted as fixed effects. Centre was fitted as a random effect except in cases where the statistical software did not support this approach, in which case robust standard errors clustered by center were used. For longitudinal continuous outcomes, hierarchical mixed models were fitted with participant nested by centre and gradients allowed to vary across time for each participant. Time was modelled with treatment-specific restricted cubic splines. Generalised linear models were used to estimate treatment effects for binary and count outcomes. Pre-specified subgroup analyses (by diabetes status at baseline and BMI category <40 kg/m2, 40–50 kg/m2 and >50 kg/m2) and sensitivity analyses were performed for the primary outcomes (appendix pp 38–41). Analyses of the primary outcomes adjusting for design phase (randomisation to two groups or randomisation to three groups), restricting the analyses to the three-group randomisation phase, and comparing outcomes in the per-protocol population were post hoc. Missing data for the primary weight outcome were imputed using multiple imputation with results combined using Rubin’s rules (appendix pp 9–11). Results are presented as treatment effects with 98% CIs. Analyses were performed using Stata (version 18.0).

Detailed information about the economic evaluations, including a wide range of sensitivity analyses, are described in the appendix (pp 12–17). The primary objective of the economic evaluation was to compare the cost-utility of Roux-en-Y gastric bypass, adjustable gastric banding, and sleeve gastrectomy to 3 years from a UK NHS perspective. The primary analysis was a within-trial analysis performed on an ITT basis, effectively estimating the cost-effectiveness of the decision to perform surgery. Quality-adjusted life-years (QALYs) were estimated using the EQ-5D-5L utility score and expressed in monetary terms by multiplying QALYs gained by the willingness to pay per QALY. Total costs included surgical procedure costs,15 and health-care costs related to hospital admissions, outpatient visits, accident and emergency visits, primary care visits, and use of medication and supplements. Costs and outcomes after the first year were discounted at an annual rate of 3·5%. The incremental net monetary benefit was estimated by fitting separate linear regression models for costs and QALYs adjusting for the cohort minimisation variables, treatment allocation, and baseline quality-of-life. Correlation between costs and QALYs was accounted for using non-parametric clustered bootstrapping with a single imputation nested within each bootstrap. The probability of each intervention being the most cost-effective option was also estimated (appendix pp 12–17). In the UK, thresholds of £20 000 and £30 000 per QALY are typically used to support NHS decision making, and the cost-utility at these thresholds was considered. All health economic analyses were performed in R (version 4.0.1).

Role of the funding source

The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Results

Out of 6961 patients screened, 4140 were eligible and were offered participation. Reasons for ineligibility are given in the appendix (pp 22). Among those who were eligible, 1351 (33%) of 4140 were randomly assigned between Jan 16, 2013, and Sept 27, 2019. Five participants subsequently withdrew consent to use all data. Therefore, 1346 participants were included in this report; 462 were randomly assigned to Roux-en-Y gastric bypass, 464 to adjustable gastric banding, and 420 to sleeve gastrectomy, with 1159 (86%) of 1346 remaining in follow-up at 3 years (figure 1).

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