Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes
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Obesity, which has evolved globally since the 1970s, is considered a complex, serious, and chronic disease that requires prevention and management strategies at the individual, societal, and national levels. The population living with obesity has increased in many countries to date, and the World Health Organization has declared it a chronic relapsing progressive disease process with cultural, social, genetic, and biological etiologies.1,2 There are several obesity-related comorbidities, such as metabolic syndrome, mental disorders, coagulopathy, malignancies, and diseases of many systems, including dermatological, musculoskeletal, cardiopulmonary, hepatobiliary, urogenital, and reproductive organs. If the trend continues globally, the estimated overweight population could reach 2.7 billion in 2025 and its-related yearly healthcare cost would be approximately 1.2 trillion United States dollars.1,2 By 2025, the prevalence of obesity worldwide is predicted to reach 18% in men and surpass 21% in women, with many countries experiencing much higher levels.1,2 Owing to a westernized lifestyle and dietary habits, obesity and its related comorbidities have become an important healthcare problem not only in Western regions but in Eastern countries, including Taiwan.3 Between the periods 2013–2016 and 2017–2020, the prevalence of obese adult populations in men and women have increased from 53.4% to 58.4% and 38.3% to 42.6%, respectively, which are much higher than the average global data.3 Therefore, the prevention and control of obesity is of paramount importance to improve human health.
Previously, therapeutic approaches for obesity started with exercise and dietary and behavioral interventions. However, only 2% to 10% of total body weight loss (TBWL) could be achieved by means of natural weight control methods. At least more than 10% TBWL must be achieved to effectively improve obesity-related comorbidities.4 Currently, anti-obesity medication (AOM), especially glucagon-like peptide-1 and its combination with other entero-pancreatic hormones for complementary actions or synergistic potential (such as glucose-dependent insulinotropic polypeptide, glucagon, and amylin), have been introduced and used widely for weight and metabolic syndrome control.4 However, numerous adverse events (AEs), particularly nausea and vomiting, as well as tachyphylaxis development have been observed in patients with obesity under AOM. Patients who did not respond to conservative management are referred for invasive bariatric surgery. Nevertheless, less than 2% of eligible patients who fulfill the criteria for bariatric surgery undergo the procedure.4,5 The factors influencing surgical decision-making include medical history and obesity-related comorbidities, surgical and anesthetic risks, patients’ lifestyles, commitment to long-term changes and desire for a permanent or reversible solution, and the expertise of bariatric surgeons.4,5 Thus, there is a treatment gap between conservative management with lifestyle modification or AOM and invasive bariatric surgery. Endoscopic bariatric and metabolic therapies have emerged to fill this gap using minimally invasive and safe procedures with favorable weight control. These procedures include gastric and intestinal approaches to induce early satiation, delayed gastric emptying, and gastric remodeling with restriction of the accommodative response, followed by decreased calorie intake and alteration in gastrointestinal hormones.6 In general, approximately 10% to 20% of TBWL can be achieved at 6 to 12 months after endoscopic bariatric and metabolic therapy, and the rate of severe AEs is usually less than 2% to 5%.6 Despite its efficacy and safety, the TBWL remains lower than that of bariatric surgery. Therefore, studies on combinations of different endotherapies or the concomitant use of AOM are under investigation to provide additional benefits for weight and metabolic syndrome control.
This study aimed to evaluate the efficacy and safety of combining endoscopic sleeve gastroplasty (ESG) with AOM for obesity control. This retrospective study was conducted between February 2022 and March 2024 at a tertiary center in Taiwan. The requirement for informed consent was waived because of unidentifiable information from the data analyzed. Patients with obesity who underwent ESG alone or a combination of ESG and oral semglutide (Rybelsus, Novo Nordisk Inc.), a glucagon-like peptide-1 analog, were enrolled in the analysis. All patients fasted overnight and underwent ESG using an OverStitch Sx suturing system (Apollo Endosurgery Inc.) under endotracheal deep general anesthesia in the supine position. A single dose of intravenous cefazolin (1 g) was administered intraprocedurally, and oral proton pump inhibitors were administered for 8 weeks after ESG. The suturing pattern was “U-shape” from the incisura angularis to upper body, sparing the fundus, to achieve a reduced volume of approximately 50% to 70% of the stomach (Fig. 1). In the absence of any procedure-related complications, all patients resumed enteral feeding on the day after ESG with a 1-week liquid diet and 1-week semi-liquid diet, followed by gradual advancement to a weight control diet. In the combination group, all patients received oral Rybelsus 14 mg/day starting from the second week of ESG. A total of 18 patients (10 female and 8 male) with a median age and body mass index of 43.5-year-old and 34.19 kg/m2, respectively, were enrolled. Ten and eight patients underwent ESG alone and ESG combined with AOM, respectively (Table 1). There were no statistically significant differences between the two groups in terms of age, sex, or baseline body mass index. Before ESG, 13 (72.22%), 3 (16.67%), 1 (5.56%), and 1 (5.56%) patients failed to undergo lifestyle/dietary modification, AOM, intragastric botulinum toxin injection, and gastric banding surgery, respectively. The technical success rate was 100%, with a median procedure time of 70 min. Endoscopically manageable intraprocedural bleeding occurred in one patient (5.56%). Overall, body mass index (mean, 27.69 vs. 34.17 kg/m2; p<0.001) as well as metabolic dysfunction improved at 6 months after ESG, particularly for hemoglobin A1c (HbA1c) level (mean, 7.2% vs. 6.3%; p=0.001). The mean total and excess weight loss at 1, 3, and 6 months were all higher in the combination therapy group, with delta values of 4.03% (p=0.005) and 8.63% (p=0.023), 4.71% (p=0.013) and 12.21% (p=0.024), and 4.95% (p=0.015) and 9.99% (p=0.034), respectively (Table 1, Fig. 2). None of the enrolled patients underwent postoperative endoscopy during the follow-up period. No differences were observed in AEs between the ESG alone and combination therapy groups (Table 1).
Endoscopic sleeve gastroplasty (ESG) procedure. (A) “U-pattern” starting from anterior wall of the incisura angularis. (B) Suturing of anterior wall, greater curvature, and posterior wall then back to greater curvature and anterior wall side of the gastric body. (C) Cinching after the suture was pulled tight. (D) Repetitive “U-pattern” suturing with additional stitches. (E) Gastric remodeling after ESG. (F) Volume reduction determined by barium X-ray examination.
Demographic data and outcomes between endoscopic sleeve gastroplasty alone and combination group of ESG and anti-obesity medication
Comparison of total body weight loss (TBWL) and excess body weight loss (EBWL) between endoscopic sleeve gastroplasty (ESG) alone and combination of ESG and anti-obesity medication.
A meta-analysis of 1,772 patients from eight original articles showed that TBWL of 8.77%, 11.28%, 15.14%, 16.50%, and 17.15% could be achieved by ESG at 1, 3, 6, 12, and 18 to 24 months, respectively, after the procedure.7 Additionally, it is not only an efficient gastric approach method among endoscopic bariatric and metabolic therapies but also a safe alternative to bariatric surgery with severe AEs rate of 2.2% and zero mortality reported.7 With weight loss after ESG, comorbidities control with 7.8% reduction in HbA1c level and remission of hypertension, dyslipidemia, and obstructive sleep apnea by 62.8%, 56.3%, and 51.7% respectively, were reported in a meta-analysis of 7,525 patients.8 Recent advancements in AOM provide additional benefits in obesity control through conservative management. A Brazilian retrospective study of prospectively collected data from patients undergoing ESG revealed superior TBWL at 7 months (20.51% vs. 24.72%, p<0.001) after initiation of liraglutide at 5 months after ESG.9 Another large-scale study of 1,506 patients from a cohort in USA found that patients who were on an active AOM at the time of ESG had a significant lower TBWL than those not on AOM at 6 months after the procedure.10 Regarding durability, patients who were prescribed glucagon-like peptide-1 receptor analogs exhibited a trend towards increased weight loss at 18 and 24 months.10 No significant AEs from AOM were reported on combining ESG and pharmacotherapy. These data indicate that additional weight loss can be achieved after ESG with the use of AOM. Further studies are warranted to determine the optimal dose, timing, duration, and type of AOM with different mechanisms for ESG combination therapy.
Our brief report had some limitations. The number of enrolled patients was small because ESG is costly and is not reimbursed by the National Health Insurance, and this was a retrospective study. Nevertheless, to the best of our knowledge, this is the first case report combining ESG and AOM for obesity management in an Asian population.
In conclusion, the combination of ESG with AOM resulted in superior efficacy for weight loss and improved diabetes control. No additional adverse effects were observed on combining AOM for patients with obesity who underwent ESG. Further studies are warranted to define the predictors for patients who benefit from combination therapy.
Notes
Conflicts of Interest
Chen-Shuan Chung is currently serving as an associate editor of Clinical Endoscopy; however, he had not involved in the peer reviewer selection, evaluation, or decision process of this article. The other authors have no potential conflicts of interest.
Funding
None.
Author Contributions
Conceptualization: all authors; Data curation: CSC, HFC, JMW; Formal analysis: CSC; Methodology: CSC, JMW; Writing–original draft: CSC; Writing–review & editing: all authors.