Why are weight loss outcomes unequal despite similar reductions in gastric volume?

Although considered by many as unjustified, the perception of bariatric surgery by patients and healthcare providers remains poor [1]. Therefore, the development of non-surgical minimally invasive strategies that alter the gastrointestinal tract to induce the physical and physiologic effects of bariatric surgery is required. An endoscopic technique that exclusively emulates the physical elements of surgery (restriction/volume reduction) will not fully reproduce the weight loss and metabolic benefits observed by patients undergoing the most commonly performed bariatric surgery, namely laparoscopic sleeve gastrectomy (LSG) [2]. However, until the precise pathologic mechanisms causing the profound physiologic alterations are discovered, the next best alternative is to offer an appealing, safe, well-tolerated, and effective technique that at least imitates the physical appearances of bariatric surgery, such as endoscopic sleeve gastroplasty (ESG) [3].

“ESG appears to offer patients who are not candidates for or simply do not want to undergo bariatric surgery (for fear of short- and long-term complications) an appealing, safe, well-tolerated, and effective option.”

In this issue of Endoscopy, Lopez-Nava et al. report the medium- to long-term results of a retrospective review of three procedures (two surgical [LSG and laparoscopic greater curvature plication (LGCP)] and one endoscopic [ESG]) that result in similar reductions in the gastric volume, as shown in Fig. 2 in their article [4]. Though the patient populations were unmatched, the strengths of this study are the similar post-procedure follow-up undertaken by all participants and the 2-year duration of follow-up. The authors arguably report the results in a somewhat biased manner by highlighting the clinically significant weight loss, shorter hospital stay, faster procedure time, and superior safety profile of ESG, instead of focusing on the primary outcome of the study – the comparative effectiveness of ESG vs. LGCP vs. LSG with respect to weight loss [4]. Nonetheless, despite the inferior efficacy of ESG compared with LSG and LGCP, it may be a cost-effective approach (at least in those who are non-morbidly obese and without severe metabolic disease, such as insulin-dependent diabetes mellitus) and further study with respect to this is warranted. Regardless of its cost-effectiveness, ESG appears to offer patients who are not candidates for or simply do not want to undergo bariatric surgery (for fear of short- and long-term complications) an appealing, safe, well-tolerated, and effective option.

There are several insights that can be derived from comparative studies such as the one published [4]. First, the data acquired can be used by clinicians and patients to allow a data-driven conversation when deciding which weight loss technique should be performed. Second, comparative data may allow a personalized approach to care. For example, data comparing ESG with LSG may reveal a lower incidence of gastroesophageal reflux disease (GERD) and post-procedure bleeding [5]. Therefore, when patients are considering their best approach, they can make informed decisions as to their choice of procedure based on the effectiveness and safety profile. Finally, comparative studies are often hypothesis generating, which can stimulate further thought into the mechanisms by which bariatric surgery induces its benefits. By understanding the pathologic mechanisms, a more simplistic/less invasive approach can be developed to achieve similar weight loss and metabolic outcomes.

A fascinating observation in the study of Lopez-Nava et al. was that, as early as 6 months after the procedure, a 10 % total body weight loss benefit was established for LSG and LGCP over ESG, which persisted through the 2 years of follow-up, as shown in Fig. 3 in their article [4]. If the variance observed was the result of suture dehiscence and loss of restriction in the ESG cohort over time, one might expect the weight loss profiles to be similar at 6 months between the three cohorts, with this being followed by the surgical cohorts steadily tracking superior weight loss over the remaining 18 months. The fact that this was not the case is further validation that the mechanism of action of bariatric surgery is more than a forced limitation in oral intake.

Lopez-Nava et al. did not investigate if there were any differences observed in the metabolic and gut hormone profile between the three cohorts [4]. However, they did previously evaluate the gut hormone profile in a small study comparing LSG with ESG [6]. They demonstrated that LSG resulted in a superior reduction in ghrelin and a greater increase in PYY and adiponectin when compared with ESG. This may explain why patients in this study who underwent LSG and LGCP were not constantly ravenous, a situation that was observed despite these patients losing > 25 % of their total body weight by 6 months [4]. Together, these findings may provide insights into why LSG confers superior weight loss to ESG and may even explain the superior weight-independent benefits that are presumed to occur with LSG in comparison to ESG.

Although LGCP is rarely performed, its superiority with respect to weight loss over ESG observed in this study is intriguing. The major difference between these two techniques appears to be the dissection of the greater curvature aspect from the omentum during LGCP. The take-down of a significant portion of the stomach’s neurovascular supply may explain the observed difference. This may result in a variation in gastric emptying and gut hormone levels, as well as other changes that could explain the superiority of LGCP over ESG.

The aforementioned observations should trigger scientists, clinicians, and industry to avoid focusing their efforts on developing endoscopic procedures that merely imitate the restrictive aspects of bariatric surgery in favor of mimicking the changes in cellular and metabolic signaling. Why are weight loss outcomes unequal despite similar reductions in gastric volume? The answer may be explained by physiologic changes, such as accelerated nutrient flow, as well as gastric emptying, loss of nutrient exposure to the gastric and small-bowel mucosa, and alterations in the microbiome and bile acid metabolism. Emerging techniques that try to emulate the above physiologic changes by targeting the neurohormonal aspects of the proximal luminal gastrointestinal tract (mucosal surfaces of the stomach and duodenum) are being developed with early results suggesting possible weight-independent metabolic benefits [7] [8] [9] [10].

Publication History

Article published online:
25 February 2021

• References

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