# The future of bariatric surgery research: A worldwide mapping of registered trials

Claire Rives-lange, Tigran Poghosyan, Nathalie Rassy, Claire Carette, Aurelie Phan, Marc Goeau-brissonnière, Flore Castelbajac, Amel Merazka, Sebastien Czernichow

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Claire Rives-lange, Tigran Poghosyan, Nathalie Rassy, Claire Carette, Aurelie Phan, et al.. The future of bariatric surgery research: A worldwide mapping of registered trials. Obesity Reviews, 2022, 23 (6), 10.1111/obr.13433. hal-04076288

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1 **The future of bariatric surgery research: a worldwide mapping of registered trials**

2 Claire Rives-Lange¹,²,³, Tigran Poghosyan⁴,², Nathalie Rassy⁵, Claire Carette¹,²,⁶, Aurelie

3 Phan¹, Marc Goeau-Brissonnière¹, Flore de Castelbajac¹, Amel Merazka¹, Sebastien

4 Czernichow¹,²,³

5 ¹Assistance Publique-Hôpitaux de Paris (AP-HP), Nutrition Department, European Hospital Georges

6 Pompidou, Paris, France

7 ²University of Paris, Paris, France

8 ³INSERM, UMR1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS),

9 METHODS team, Paris, France

10 ⁴Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Digestive Surgery, European Hospital

11 Georges Pompidou, Paris, France

12 ⁵Department of Cancer Medicine, Gustave Roussy, Villejuif, France

13 ⁶Clinical Investigation Center 1418, Assistance Publique-Hôpitaux de Paris (AP-HP), European

14 Hospital Georges Pompidou, Paris, France

15 **Word count for the main text:** 1895

16

17 **Abstract**

18 **Introduction:**

19 The bariatric surgery (BS) research landscape is a continuous evolving. Since the first described
20 procedure, numerous different techniques have been developed by surgical teams. In this
21 context, we conducted a systematic mapping of upcoming randomized controlled trials (RCTs)
22 in bariatric surgery for people with obesity.

23 **Methods:** In June 2021, we performed a systematic review of RCTs evaluating BS versus
24 another surgical procedure or versus a medical control group, through a search in
25 ClinicalTrials.gov. There was no restriction on outcomes for study selection.

26 **Results:** A total of 62 RCTs were included, totalling 10,800 potential individuals to be
27 included, with planned Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy surgeries
28 the most common. The median number of patients planned to be enrolled is 78 (IQR: 50 -143).
29 Mean follow-up time is 12 months in 55% of trials and 4 years or more in 23%. The most
frequent (81% of RCTs) outcomes to be investigated are obesity-related diseases with the study of type 2 diabetes, followed by weight loss, quality of life and surgical complications.

**Discussion-Conclusion:** The rising number of BS procedures around the world has been followed by a subsequent surge in BS research. An increase in interest is observed in outcomes such as obesity-related diseases, intermediate metabolic markers, quality of life and body composition.

36

37

## 38 Introduction

39

The prevalence of obesity has increased worldwide to pandemic proportions since the beginning of the 1980s, with more than 2 billion people affected<sup>1,2,3</sup>. Among the different therapeutic options, bariatric surgery (BS) remains an effective treatment for patients with severe obesity engaged in a lifelong nutritional follow-up and leads to an increase in life expectancy<sup>4,5,6</sup>. Since the beginning of BS in 1950<sup>7</sup>, numerous papers have been published on this field of interest<sup>8,9</sup>, with some surgical procedures still being used and others abandoned<sup>10</sup>. In the meantime, innovative surgical procedures are being evaluated, or even performed while being evaluated, such as sleeve gastrectomy with transit bipartition (SG-TBP) and single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-SG)<sup>11,12</sup>. The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) survey in January 2021 reported a total of 604,223 yearly primary interventions worldwide<sup>13</sup>, with sleeve gastrectomy remaining the most commonly performed. Current international guidelines target BS for patients with body mass index (BMI) ≥40 kg/m<sup>2</sup> or those with BMI ≥35–40 kg/m<sup>2</sup> with associated comorbidities<sup>14</sup>. It is in this context of evolution of surgical practices and of possible change of interest for the investigation of new outcomes within a growing phase of research
55 production, that we systematically mapped upcoming randomized controlled trials (RCTs) in
56 BS, in order to clarify the future of research in this field.

57
58

## 59 **Materials and Methods**

60 **Search strategy.** In June 2021, we performed a systematic review of RCTs evaluating BS in
61 patients with obesity through a clinical trials registry search (ClinicalTrials.gov). This platform
62 is under the responsibility of the U.S. government and has a mechanism to ensure the validity
63 of the registration data¹⁵. We used the 2015 Medical Subject Headings (MeSH), from the U.S.
64 National Library of Medicine, as already done in other mapping research¹⁶. The iterations used
65 were "bariatric surgery" OR "adjustable gastric banding" OR "sleeve gastrectomy" OR "Roux
66 Y gastric bypass" OR "one anastomosis gastric bypass" OR "biliopancreatic derivation with
67 switch duodenal" OR "duodenal switch" OR "single loop duodeno-jejunal bypass with sleeve
68 gastrectomy" single anastomosis duodeno-ileal bypass with sleeve gastrectomy" OR "single
69 anastomosis duodeno-ileal bypass with duodenal switch" OR "sleeve gastrectomy with transit
70 bipartition".

71 We followed the last PRISMA statement¹⁷ for conducting and reporting systematic reviews.
72 We selected trials not yet published, with manual verification for each trial, comparing two
73 primary BS techniques or primary BS versus a medical intervention, in the adult population.
74 There was no restriction on outcomes for study selection. Two reviewers independently
75 checked the studies against the prespecified eligibility criteria.

76 **Data collection.** We investigated the trials' main features, including the comparisons,
77 interventions, location, status, number of patients planned to be enrolled, and follow-up time.
78 Regarding the inclusion criteria, we collected inclusion or exclusion criteria for age, BMI and
79 diabetic status. We also collected all pre-defined primary and secondary outcomes and
classified them according to the following categories: efficacy, surgery and perioperative period, mortality, complications and tolerance. The first "efficacy" category included weight loss, obesity-related diseases with cardiovascular risk factors (hypertension, type 2 diabetes, dyslipidaemia), cardiovascular events, the occurrence of cancer, respiratory, renal, cardiac, liver function, arthrosis and intermediate metabolic markers (glucose homeostasis, beta cell function, insulin resistance, inflammation, regulation of hunger, gut hormones and gut microbiota), eating behaviour, energy expenditure and health costs. The second category included associated procedure, length of surgery and of anaesthesia, length of hospital stay, conversion to open surgery, pulse rate, grip force testing during perioperative time, oxygen saturation during perioperative time, analgesic usage, blood loss and early complications. The second category was the mortality at different time after BS. The fourth category of complications was divided into medical and surgical complications (such as, in particular, the Dindo-Clavien classification). The last category was the tolerance of BS who included quality of life, general satisfaction and gastro-intestinal symptom (see results section, Figure 4)

**Statistical analysis.** Data are summarized as number (%) for qualitative variables and median (Q1-Q3) for continuous variables. All statistical analyses were conducted using R studio software version 3.3.2 (http://www.r-project.org)

**Data visualization.** The different graphic representations were made with Adobe Illustrator®, InDesign® software (https://www.adobe.com/).

**Results**

**Systematic literature search**
104 The study flowchart is presented in Figure 1. The electronic search yielded 142 references found on clinicaltrials.gov. Of these, 20 were not randomized, 38 were duplicates and 22 were excluded since they were already published. A total of 62 studies were included in the current report (Supplemental material 1 listed all the studies included).

108

109 **Characteristics of the trials**

110 Among the 62 eligible studies identified (Table 1), Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the procedures that will be the most studied (n=39 trials, 62.9% of all studies recorded), while one anastomosis gastric bypass (OAGBP) and adjustable gastric banding (AGB) represent 11.3% and 8.1% of all trials, respectively. Additionally, recent surgeries such as single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-SG) and sleeve gastrectomy with transit bipartition (SG-TBP) represent 8.1% and 3.2%, respectively. Half of trials are designed to be conducted in Europe (Figure 2). Most trials (63%) used a surgical comparator versus 48% for a medical comparator. The median number of patients enrolled was 78 (IQR: 50-143). Follow-up time was one year for more than half of studies (55%) (Table 1).

120

121 **Characteristics of the population**

122 Nearly a third of trials (29%) focused only on the diabetic population. The most studied age category was [18-70 years] for the vast majority of trials and BMI category was ≥35 kg/m² for 60% of trials. Only 3% of trials plan to include in the age category [65-80 years] 28% and 3%, respectively, for the BMI categories ≥25/30 kg/m² and ≥50 kg/m².

126

127 **Analysed outcomes**
We investigated the range of outcomes evaluated in all trials. Figure 4 shows that the most studied criterion was obesity-related diseases, in 80.6% of RCTs, followed by weight loss, tolerance, surgical complications and intermediate metabolic markers, medical complications, mortality, and body composition. Concerning the study of surgical complications, the Dindo-Clavien classification was used in 12.9% of cases, and for perioperative time the Benchmark outcomes was not used. Figure 5 details the obesity-related diseases, medical complications, intermediate metabolic markers and tolerance outcomes. Obesity-related diseases were mostly represented by the study of type 2 diabetes (62.9%), dyslipidaemia (45.2%), hypertension (33.9%), respiratory function (21%) and liver function (17.7%). Among medical complications, nutritional deficiencies, sarcopenia and mental health were studied in 19.4% of trials and in 3.2% for the last two. Among the outcomes of tolerance of BS, quality of life criteria reached 37%.

140
141
142 **Discussion**

143 Our study reports the first systematic mapping of upcoming RCTs in BS and highlights future
144 research efforts of primary or secondary outcome investigations. This synthesized vision of
145 future research is intended to guide researchers in the field of BS.

146 This review highlights the dynamism of this fast-growing surgical field, as indicated by the
147 large number of RCTs in the pipeline. This evolution is in line with the trend of the last decade
148 in terms of scientific production in BS¹³,¹⁸.

149 We have observed an uneven distribution of RCTs and of contributions to research around the
150 world. Europe and North America remain the most active regions in research. It is nevertheless
151 remarkable that RCTs are emerging in the African continent, a region that was previously
152 absent in the scientific production of RCTs in BS.

153 SG and RYGB were the most studied surgical procedures. The former¹⁸ is currently the most
154 commonly performed bariatric procedure according to the latest data, and the latter remains
155 highly studied. It should be noted that most recent surgeries such as SADI-S, SLDJBP-SG and
156 SG-TB are now the subject of RCTs.

157 The surgical control group remains the most frequent. The median sample size in future RCTs
158 is low compared to samples of medical research¹⁹, but comparable to research in other surgical
159 topics²⁰. More than half of trials will not exceed one year of follow-up and only a quarter are
160 designed to extend beyond four years. We can challenge the overall concept of designing and
161 conducting trials for several months only, given that BS addresses a lifelong chronic disease.

162 Regarding the outcomes studied in these upcoming RCTs, weight loss was no the longer the
163 most studied outcome, which was obesity-related diseases in 81% of trials, including an
164 increasing emphasis on the impact of BS on liver function. Interestingly, more than one-third
165 of these trials were focused on the study of intermediate metabolic markers, which supports the
166 fact that, beyond weight reduction, the additional beneficial effects of BS on homeostasis
provide a rationale for the rise of metabolic surgery<sup>21,23</sup>. Increasing attention is being given to
change in body composition, which is of importance since it allows the definition of
undernutrition in recent international guidelines<sup>22</sup>. The tolerance of BS was evaluated in nearly
half of the trials, with an increasing focus on quality of life evaluation. A large field of study
regarding nutritional deficiency risk or mental health remains under-investigated. Furthermore,
given the potential consequences of nutritional deficiency<sup>24</sup> and the worrying appearance of
depressive syndrome or addiction after BS<sup>24</sup>, it seems necessary to pay specific attention to
their evaluation.

A limitation of this study is that our systematic review focused only on RCTs and therefore
provides a fragmented view of future research in the field of BS. This methodological choice
was underpinned by the level of evidence of these studies. Indeed, evidence from RCTs is
considered to be at the top of the evidence pyramid. It is recommended that clinical practice
decisions be based on evidence emanating from well-conducted RCTs<sup>23</sup>. Another limit was that
these studies are not guaranteed to be published in the future.

181

182 **Conclusion**

We performed a systematic mapping of upcoming RCTs in the field of research on BS. The
increase of BS around the world and the emergence of new BS procedures have been followed
by a similar dynamism in research in BS. Increasing attention is being paid to obesity-related
diseases, intermediate metabolic markers, quality of life after BS and body composition.
However, some methodological aspects of these trials, such as limited follow-up time, need to
be improved. In order to limit waste in research that replicates an existing body of evidence and
to provide answers to questions that have not yet been addressed, future studies on BS should
reconsider the points raised in the current paper.

191
192 Acknowledgements

193 We thank Fanny Naranjo for graphic design and David Marsh PhD for language editing and

194 proofreading.

195

196

197 Funding

198 This study was conducted without funding
<table><caption>Table 1. Characteristics of the studies and populations of future randomized controlled trials in bariatric surgery</caption><thead><tr><th></th><th>All</th><th colspan="3">Restrictive surgeries</th></tr><tr><th>Names of surgeries</th><th></th><th>AGB</th><th>SG</th><th>N-SG</th></tr></thead><tbody><tr><td>Number of studies (n, %)</td><td>62</td><td>5 (8.1%)</td><td>39 (62.9%)</td><td>1 (1.6%)</td></tr><tr><td>Status of trials (n, %)</td><td></td><td></td><td></td><td></td></tr><tr><td>Active, not recruiting</td><td>10 (16.4%)</td><td>1 (20.0%)</td><td>5 (13.0%)</td><td>0</td></tr><tr><td>Not yet recruiting</td><td>8 (13.0%)</td><td>0</td><td>6 (15.0%)</td><td>1 (100%)</td></tr><tr><td>Recruiting</td><td>23 (37.0%)</td><td>1 (20.0%)</td><td>19 (49.0%)</td><td>0</td></tr><tr><td>Completed</td><td>12 (19.0%)</td><td>2 (40.0%)</td><td>8 (21.0%)</td><td>0</td></tr><tr><td>Terminated</td><td>1 (1.6%)</td><td>1 (20.0%)</td><td>0</td><td>0</td></tr><tr><td>Unknown</td><td>8 (13.0%)</td><td>0</td><td>1 (2.6%)</td><td>0</td></tr><tr><td>Location (n, %)</td><td></td><td></td><td></td><td></td></tr><tr><td>North America</td><td>13 (21.0%)</td><td>3 (60.0%)</td><td>6 (15%)</td><td>0</td></tr><tr><td>South America</td><td>6 (9.7%)</td><td>0</td><td>2 (5.1%)</td><td>0</td></tr><tr><td>Europe</td><td>31 (50.0%)</td><td>2 (40.0%)</td><td>20 (51%)</td><td>1 (100.0%)</td></tr><tr><td>Asia</td><td>7 (11.0%)</td><td>0</td><td>6 (15.0%)</td><td>0</td></tr><tr><td>Oceania</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Africa</td><td>5 (8.1%)</td><td>0</td><td>5 (13.0%)</td><td>0</td></tr><tr><td>Number of participants (median, IQR)</td><td>78 (50, 143)</td><td>100 (60, 197)</td><td>80 (50, 139)</td><td>144 (144, 144)</td></tr><tr><td>Age of population (n, %)</td><td></td><td></td><td></td><td></td></tr><tr><td>[18-70 years]</td><td>58 (94.0%)</td><td>5 (100.0%)</td><td>37 (95.0%)</td><td>1 (100.0%)</td></tr><tr><td>[18-40/50 years]</td><td>3 (4.8%)</td><td>0</td><td>1 (2.6%)</td><td>0</td></tr><tr><td>[65-80 years]</td><td>1 (1.6%)</td><td>0</td><td>1 (2.6%)</td><td>0</td></tr><tr><td>BMI (n, %)</td><td></td><td></td><td></td><td></td></tr></tbody></table>
<table><tr><td>≥35 kg/m²</td><td>37 (60.0%)</td><td>3 (60.0%)</td><td>25 (64.0%)</td><td>1 (100.0%)</td></tr><tr><td>≥25/30 kg/m²</td><td>16 (26.0%)</td><td>2 (40.0%)</td><td>9 (23.0%)</td><td>0</td></tr><tr><td>≥40/45 kg/m²</td><td>3 (4.8%)</td><td>0</td><td>1 (2.6%)</td><td>0</td></tr><tr><td>≥50 kg/m²</td><td>2 (3.2%)</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Unknown</td><td>4 (6.5%)</td><td>0</td><td>4 (10.0%)</td><td>0</td></tr><tr><td><strong>Diabetic status</strong><br/>- Studies focused on patients with diabetes only (n, %)</td><td>18 (29.0%)</td><td>2 (40.0%)</td><td>7 (18.0%)</td><td>0</td></tr><tr><td><strong>Medical control (n, %)</strong></td><td>30 (48.0%)</td><td>2 (40.0%)</td><td>16 (41.0%)</td><td>0</td></tr><tr><td><strong>Surgical control (n, %)</strong></td><td>39 (63.0%)</td><td>5 (100.0%)</td><td>26 (67.0%)</td><td>1 (100.0%)</td></tr><tr><td><strong>Follow-up times (n, %)</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>0-1 year]</td><td>34 (55.0%)</td><td>2 (40.0%)</td><td>23 (59.0%)</td><td>1 (100.0%)</td></tr><tr><td>]1-2 years]</td><td>11 (18.0%)</td><td>0</td><td>7 (18.0%)</td><td>0</td></tr><tr><td>]2-3 years]</td><td>3 (4.8%)</td><td>1 (20.0%)</td><td>3 (7.7%)</td><td>0</td></tr><tr><td>]3-4 years]</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>>4 years</td><td>14 (23%)</td><td>2 (40.0%)</td><td>6 (15.0%)</td><td>0</td></tr></table>

<table><thead><tr><th colspan="9">Malabsorptive +/- Restrictive surgeries</th></tr><tr><th>Names of surgeries</th><th>RYGBP</th><th>OAGBP</th><th>SLDJBP-SG</th><th>SADI-SG</th><th>SADI-DS</th><th>BPD-DS</th><th>DS</th><th>SG-TBP</th></tr></thead><tbody><tr><td>Number of studies (n, %)</td><td>39 (62.9%)</td><td>7 (11.3%)</td><td>3 (4.8%)</td><td>5 (8.1%)</td><td>1 (1.6%)</td><td>1 (1.6%)</td><td>3 (4.8%)</td><td>2 (3.2%)</td></tr><tr><td>Status of trials (n, %)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Active, not recruiting</td><td>8 (20.6%)</td><td>1 (14.0%)</td><td>0</td><td>0</td><td>1 (100.0%)</td><td>0</td><td>1 (33.0%)</td><td>0</td></tr><tr><td>Not yet recruiting</td><td>2 (5.1%)</td><td>0</td><td>0</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>1 (33.0%)</td><td>1 (50.0%)</td></tr><tr><td>Recruiting</td><td>16 (41.0%)</td><td>3 (43.0%)</td><td>0</td><td>2 (40.0%)</td><td>0</td><td>0</td><td>1 (33.0%)</td><td>1 (50.0%)</td></tr><tr><td>Completed</td><td>6 (15.0%)</td><td>3 (43.0%)</td><td>1 (33.0%)</td><td>2 (40.0%)</td><td>0</td><td>0</td><td>0</td><td>0</td></tr></tbody></table>
<table><tbody><tr><td>Terminated</td><td>1 (2.6%)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Unknown</td><td>6 (15.0%)</td><td>0</td><td>2 (67.0%)</td><td>0</td><td>0</td><td>1 (100.0%)</td><td>0</td><td>0</td></tr><tr><td>Location (n, %)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>North America</td><td>9 (23.0%)</td><td>0</td><td>0</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>1 (33.0%)</td><td>0</td></tr><tr><td>South America</td><td>5 (13.0%)</td><td>0</td><td>1 (33.0%)</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Europe</td><td>22 (56.0%)</td><td>3 (43.0%)</td><td>0</td><td>2 (40.0%)</td><td>1 (100.0%)</td><td>1 (100.0%)</td><td>2 (67.0%)</td><td>1 (50%)</td></tr><tr><td>Asia</td><td>3 (7.7%)</td><td>0</td><td>1 (33.0%)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Oceania</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Africa</td><td>0</td><td>4 (57.0%)</td><td>1 (33.0%)</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>0</td><td>1 (50.0%)</td></tr><tr><td>Number of participants (median, IQR)</td><td>76 (50, 137)</td><td>186 (120, 505)</td><td>80 (52, 145)</td><td>186 (140, 382)</td><td>56 (56, 56)</td><td>60 (60, 60)</td><td>140 (98, 163)</td><td>235 (192, 278)</td></tr><tr><td>Age of population (n, %)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>[18-70 years]</td><td>36 (92.0%)</td><td>7 (100.0%)</td><td>3 (100.0%)</td><td>5 (100.0%)</td><td>1 (100.0%)</td><td>0</td><td>3</td><td>2 (100.0%)</td></tr><tr><td>[18-40/50 years]</td><td>2 (5.1%)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>1 (100.0%)</td><td>(100.0%)</td><td>0</td></tr><tr><td>[65-80 years]</td><td>1 (2.6%)</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>BMI (n, %)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>≥35 kg/m²</td><td>23 (59.0%)</td><td>3 (43.0%)</td><td>1 (33.0%)</td><td>2 (40.0%)</td><td>0</td><td>0</td><td>1 (33.0%)</td><td>1 (50.0%)</td></tr><tr><td>≥25/30 kg/m²</td><td>11 (28.0%)</td><td>0</td><td>2 (67.0%)</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>≥40/45 kg/m²</td><td>2 (5.1%)</td><td>1 (14.0%)</td><td>0</td><td>0</td><td>1 (100.0%)</td><td>0</td><td>1 (33.0%)</td><td>0</td></tr><tr><td>≥50 kg/m²</td><td>1 (2.6%)</td><td>1 (14.0%)</td><td>0</td><td>1 (20.0%)</td><td>0</td><td>1 (100.0%)</td><td>1 (33.0%)</td><td>0</td></tr><tr><td>Unknown</td><td>2 (5.1%)</td><td>2 (29.0%)</td><td>0</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>0</td><td>1 (50.0%)</td></tr><tr><td>Diabetic status - Studies focused on diabetic population (n, %)</td><td>14 (36.0%)</td><td>1 (14.0%)</td><td>2 (67.0%)</td><td>2 (40.0%)</td><td>0</td><td>0</td><td>0</td><td>0</td></tr></tbody></table>
<table><tr><td>Medical control (n, %)</td><td>23 (59.0%)</td><td>0</td><td>1 (33.0%)</td><td>1 (20.0%)</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Surgical control (n, %)</td><td>23 (59%)</td><td>7 (100.0%)</td><td>2 (67.0%)</td><td>5 (100.0%)</td><td>1 (100.0%)</td><td>1 (100.0%)</td><td>3 (100.0%)</td><td>2 (100.0%)</td></tr><tr><td>Follow-up times (n, %)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-2 year]</td><td>21 (54.0%)</td><td>4 (57.0%)</td><td>1 (33.0%)</td><td>1 (20.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>1 (50.0%)</td></tr><tr><td>1-2 years]</td><td>7 (18.0%)</td><td>1 (14.0%)</td><td>2 (67.0%)</td><td>2 (40.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>1 (50.0%)</td></tr><tr><td>2-3 years]</td><td>2 (5.1%)</td><td>1 (14.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td></tr><tr><td>3-4 years]</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td></tr><tr><td>>4 years</td><td>9 (23.0%)</td><td>5 (71.0%)</td><td>0 (0.0%)</td><td>2 (40.0%)</td><td>1 (100.0%)</td><td>1 (100.0%)</td><td>3 (100.0%)</td><td>0 (0.0%)</td></tr></table>

Results are expressed by median [interquartile range] for continuous data and n (%) for categorical data.

Abbreviations:

BMI: body mass index (kg/m²)

AGB: adjustable gastric banding

SG: sleeve gastrectomy

N-SG: Nissen sleeve gastrectomy

RYGBP: Roux-en-Y gastric bypass

OAGBP: one anastomosis gastric bypass

BPD-DS: biliopancreatic derivation with duodenal switch

DS: duodenal switch

SLDJBP-SG: single loop duodeno-jejunal bypass with sleeve gastrectomy

SADI-SG: single anastomosis duodeno-ileal bypass with sleeve gastrectomy

SADI-DS: single anastomosis duodeno-ileal bypass with duodenal switch
SG-TBP: sleeve gastrectomy with transit bipartition
References

1. Swinburn, B. A. et al. The Global Syndemic of Obesity, Undernutrition, and Climate Change: The Lancet Commission report. *The Lancet* **393**, 791–846 (2019).

2. Blüher, M. Obesity: global epidemiology and pathogenesis. *Nat. Rev. Endocrinol.* **15**, 288–298 (2019).

3. Yanovski, J. A. Trends in underweight and obesity — scale of the problem. *Nat. Rev. Endocrinol.* **14**, 5–6 (2018).

4. Arterburn, D. E., Telem, D. A., Kushner, R. F. & Courcoulas, A. P. Benefits and Risks of Bariatric Surgery in Adults: A Review. *JAMA* **324**, 879 (2020).

5. Adams, T. D. et al. Weight and Metabolic Outcomes 12 Years after Gastric Bypass. *N. Engl. J. Med.* **377**, 1143–1155 (2017).

6. Syn, N. L. et al. Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. *The Lancet* **397**, 1830–1841 (2021).

7. Phillips, B. T. & Shikora, S. A. The history of metabolic and bariatric surgery: Development of standards for patient safety and efficacy. *Metabolism* **79**, 97–107 (2018).

8. Ozsoy, Z. & Demir, E. The Evolution of Bariatric Surgery Publications and Global Productivity: A Bibliometric Analysis. *Obes. Surg.* **28**, 1117–1129 (2018).

9. Ozsoy, Z. & Demir, E. Which Bariatric Procedure Is the Most Popular in the World? A Bibliometric Comparison. *Obes. Surg.* **28**, 2339–2352 (2018).

10. Poghosyan, T. et al. Roux-en-Y gastric bypass for the treatment of severe complications after omega-loop gastric bypass. *Surg. Obes. Relat. Dis.* **13**, 988–994 (2017).
11. Angrisani, L. et al. Bariatric Surgery Worldwide 2013. *Obes. Surg.* **25**, 1822–1832 (2015).

12. Angrisani, L. et al. IFSO Worldwide Survey 2016: Primary, Endoluminal, and Revisional Procedures. *Obes. Surg.* **28**, 3783–3794 (2018).

13. Angrisani, L. et al. Bariatric Surgery Survey 2018: Similarities and Disparities Among the 5 IFSO Chapters. *Obes. Surg.* **31**, 1937–1948 (2021).

14. Di Lorenzo, N. et al. Clinical practice guidelines of the European Association for Endoscopic Surgery (EAES) on bariatric surgery: update 2020 endorsed by IFSO-EC, EASO and ESPCOP. *Surg. Endosc.* **34**, 2332–2358 (2020).

15. De Angelis, C. D. et al. Is This Clinical Trial Fully Registered?: A Statement from the International Committee of Medical Journal Editors*. *Ann. Intern. Med.* **143**, 146 (2005).

16. Komenda, M. et al. Practical use of medical terminology in curriculum mapping. *Comput. Biol. Med.* **63**, 74–82 (2015).

17. Page, M. J. et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. *Int. J. Surg.* **88**, 105906 (2021).

18. Dabi, Y. et al. Publication Trends in Bariatric Surgery: a Bibliometric Study. *Obes. Surg.* **26**, 2691–2699 (2016).

19. Wilding, J. P. H. et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. *N. Engl. J. Med.* **384**, 989–1002 (2021).

20. Voineskos, S. H. et al. A Systematic Review of Surgical Randomized Controlled Trials: Part 2. Funding Source, Conflict of Interest, and Sample Size in Plastic Surgery. *Plast. Reconstr. Surg.* **137**, 453e–461e (2016).

21. Rubino, F. From Bariatric to Metabolic Surgery: Definition of a New Discipline and Implications for Clinical Practice. *Curr. Atheroscler. Rep.* **15**, 369 (2013).
22. Cederholm, T. et al. GLIM criteria for the diagnosis of malnutrition – A consensus report from the global clinical nutrition community. *J. Cachexia Sarcopenia Muscle* **10**, 207–217 (2019).

23. Nuzzo, A. et al. Prevention and treatment of nutritional complications after bariatric surgery. *Lancet Gastroenterol. Hepatol.* **6**, 238–251 (2021).

24. Dawes, A. J. et al. Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery: A Meta-analysis. *JAMA* **315**, 150 (2016).

**Figure and table legends**

- **Figure 1:** Flowchart

- **Figure 2:** Upcoming randomized clinical trials around the world

- **Figure 3:** Upcoming comparators and follow-up times

- **Figure 4:** Upcoming outcomes

- **Figure 5:** Outcomes studied in upcoming randomized controlled trials

- **Table 1:** Characteristics of the studies and populations of future randomized controlled trials in bariatric surgery