The effect of combining surgical or endoscopic bariatric interventions with anti-obesity medication or probiotics on weight loss: a narrative review

Obesity is a multifactorial chronic disease associated with multiple health complications. While bariatric surgery and endoscopic sleeve gastroplasty (ESG) are effective treatments for severe obesity, patients may still experience challenges such as weight regain or inadequate weight loss. As a result, combining these interventions with adjunctive treatment such as anti-obesity medication (AOM) or probiotics has become an area of increasing clinical interest. This narrative review summarizes the current evidence on the effect of combining surgical or endoscopic bariatric interventions with AOM or probiotics. Available studies suggest that the combination of GLP-1 receptor agonists (GLP-1 RA) and ESG leads to more weight loss than ESG alone. In contrast, non-GLP-1 RA medication show less consistent benefits and generally lower weight loss. GLP-1 RAs and tirzepatide show clinically relevant short term weight loss in patients with weight regain or insufficient weight loss after bariatric surgery. Other AOM, such as topiramate, phentermine, orlistat and bupropion/naltrexone result in more modest and variable outcomes. Relatively small studies on probiotics and prebiotics in combination with bariatric surgery do not find a statistically significant difference in weight loss between probiotic and placebo groups. Although small benefits in waist circumference, liver enzymes and vitamin uptake are mentioned, the effects are modest and not consistent across studies. In conclusion, combining AOM, especially GLP-1 RAs, with surgical or endoscopic obesity treatments appears to enhance weight loss in patients with suboptimal outcomes. These findings support the use of AOM as an adjunct to bariatric procedures. In addition, additional adequately powered studies are needed to evaluate the role for probiotics in improving weight loss after bariatric surgery. Future research should focus on long-term outcomes, side effects, and identifying patient subgroups that may benefit most from combined therapy.

Introduction

Obesity is a worldwide pandemic with an estimated one billion people affected (1). Obesity has a negative impact on multiple organ systems, leading to serious health complications. For example, obesity increases the risk of hypertension, dyslipidemia and type 2 diabetes, and as a result increased risk of cardiovascular events. Obesity can affect the respiratory system by reducing lung volumes, causing obstructive sleep apnea or have a negative impact on asthma. Obesity also affects the musculoskeletal system by increasing the risk of osteoarthritis. The gastrointestinal tract may be impacted in the case of metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux. Beyond physical health, obesity is also known to have a negative effect on the psychological well-being (2).

Bariatric surgery is the most effective therapy for severe obesity. It is associated with greater weight loss compared to combined life style interventions and pharmacologic treatment of obesity. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are the most performed interventions. Mean percentage weight loss long term after RYGB is 27.8 and 22.9 after SG (3). Other bariatric surgeries that are less frequently mentioned in this review are gastric banding, biliopancreatic diversion, gastric plication and Single Anastomosis Duodeno-Ileal bypass (SADI).

Another effective approach for weight loss is ESG, either as single intervention or in combination with anti-obesity medication (AOM). ESG is an emerging technique that reduces gastric volume by suturing the gastric body into a tubular configuration. By doing this, it mimics the restrictive effect of laparoscopic sleeve gastrectomy without anatomical resection. ESG as a single intervention reduces the total body weight by approximately 15.9% (4). Similar endoscopic procedures such as endoscopic gastric remodeling (EGR) lead to comparable results.

However, weight regain after initial normal weight loss, or insufficient weight loss after bariatric interventions, is a common problem. Most patients have some weight regain after the initial two years but still have sufficient long-term weight loss. A well-defined definition of abnormal weight regain after bariatric interventions is lacking. Nevertheless, a benchmark registry cohort of 18,403 patients shows that 12.2% achieve less than 20% weight loss compared to their starting weight. This was measured 5.2 years after surgery in context of insufficient weight loss or weight regain (5).

To address these issues, addition of pharmacologic treatment for obesity in those with insufficient weight loss after surgery or ESG is becoming more common. AOM mainly targets hormonal and neural pathways. These hormonal and neural pathways influence appetite, satiety, and glucose metabolism. GLP-1 receptor agonists (GLP-1RA), such as liraglutide and semaglutide, as well as the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA such as tirzepatide demonstrate a positive effect on bodyweight, glucose metabolism, and lipids. Other drugs such as topiramate alone or in combination with phentermine and bupropion/naltrexone show a clinically meaningful effect on weight regain. The combination of ESG in conjunction with AOM can increase weight loss to 25% (6, 7).

Obesity is associated with an altered gut microbiome composition. Therefore modifying the gut microbiome in patients with obesity by increasing the population of beneficial microorganisms has been identified as a potential strategy to increase weight loss and thereby lowering the chance of obesity related problems (8). Probiotics exhibit anti-obesity effects by regulating intestinal microflora and related metabolites, reducing insulin resistance, and enhancing satiety.

Lactobacillus and Bifidobacterium species have been used in animal models of obesity due to their low pathogenicity and strong resistance to antibiotics. Their application has resulted in varying degrees of weight and fat reduction. Bifidobacterium has been shown to reduce inflammation, insulin resistance, fat accumulation, and serum levels of cholesterol and triglycerides, primarily by decreasing intestinal permeability.

Furthermore, administering probiotics containing Lactobacillus strains to obese animals has effectively reduced body fat mass and improved both lipid distribution and blood glucose homeostasis, likely by stimulating fatty acid oxidation or inhibiting lipoprotein lipase activity (8).

It remains uncertain whether weight loss with pharmacological intervention and probiotics is the same after bariatric surgery and ESG compared to those without surgical intervention. It is important for patients and healthcare providers to understand how much weight loss they can expect from additional treatment after bariatric surgery or ESG. In this narrative review we discuss relevant articles investigating weight change in patients receiving a combination of AOM after or concomitant with bariatric interventions.

Endoscopic sleeve gastroplasty and anti-obesity medication

We identified four studies that investigated the combined use of endoscopic bariatric procedures and AOM. In all studies, AOM was initiated directly or during the first year after the intervention. These studies included a total of 1,784 patients, of whom 381 received both endoscopic and pharmacological treatment, while the other 1,403 received endoscopic treatment alone. An overview of these articles can be found in Table 1.

Table 1

Table 1. Primary endoscopic sleeve and anti-obesity medicine.

The four studies had a similar design. All of the studies are retrospective cohort studies (9–12). The most common endoscopic procedure was ESG performed with the OverStitch device. Only Jirapinyo et al. used besides the OverStitch device also the Incisionless Operating Platform. The distribution between devices was not specified (11).

All studies compared the use of GLP-1 RAs, such as liraglutide and semaglutide in combination with ESG versus ESG monotherapy. Two studies also included non-GLP-1 RA medication like phentermine, topiramate, phentermine-topiramate, bupropion-naltrexone, bupropion and orlistat, used as monotherapy or combination therapy (11, 12). One study included patients who had initiated AOM prior to ESG (11). The other studies initiated AOM at varying intervals following ESG, ranging from two weeks (10) to more than 12 months after procedure (12). Study follow-up ranged from six months (10) to 24 months (12). Two studies investigated the start of semaglutide or liraglutide at a fixed time after intervention (9, 10). Two studies investigated the effectiveness of AOM at a non-fixed time after intervention (11, 12).

The overlapping outcome of these four studies (9–12) was the percentage of total body weight loss (%TWL), which varied across the different treatment strategies.

In the ESG monotherapy groups, %TWL ranged from 15.3% to 20.5%. In the ESG plus GLP-1 RA groups, higher weight loss outcomes were observed, with %TWL ranging from 16.7% to 24.7%. Chung et al. reported 20.27% TWL while this was 23.7% ± 4.6%, 16.7% ± 11.9%, and 24.72% ± 2.12% in the studies of Jirapinyo, Gala and Badurdeen respectively. One study also reported that addition of GLP-1 RA resulted in an additional reduction of HbA1C (1.2% ± 0.13% versus 1.4% ± 0.19% after six months in the ESG monotherapy and ESG combining AOM group respectively) (10).

For patients treated with ESG combined with non–GLP-1 anti-obesity medication, %TWL ranged from 14.2% to 18.0%. Jirapinyo et al. reported 18.0% but did not differentiate between different AOMs. Gala et al. reported 14.2% ± 10.1% and did not differentiate between types of non-GLP1 RAs either. These outcomes overlap with those observed in ESG monotherapy groups. Although the data suggest a modest benefit from the addition of non–GLP-1 AOM, the effect appears less consistent and less pronounced compared to addition of GLP-1 RAs.

The results suggest that combining ESG with GLP-1 RA therapy may result in superior weight loss compared to ESG alone or ESG combined with non–GLP-1 medications. These findings support the potential additive effect of GLP-1 RAs when initiated concurrently with endoscopic intervention.

A strength of the reviewed studies is that all four were conducted in clinical practice settings, increasing the external validity of the findings. However, several limitations must be considered. All included studies were retrospective cohort studies, introducing a risk of selection bias and limiting the ability to infer causality (9–12). In addition, none of the studies used randomization or blinding, and the timing of AOM initiation varied significantly, from two weeks to over 12 months post-ESG (8, 11). This heterogeneity may have influenced treatment effects and complicates direct comparison between studies. Furthermore, none of the studies included a standardized protocol for AOM type or dosage, and only limited information was available on patient adherence. Whether combination of ESG and AOM leads to additional and specific side effects is not reported. The limited follow-up duration in these studies (as short as seven months) also restricts conclusions on long-term efficacy. Future prospective studies on ESG combined with AOM with standardized initiation of AOM, defined medication protocols, side effects and longer follow-up are warranted to confirm these findings.

Bariatric surgery and AOM

A total of 25 articles encompassing a total of 3,588 patients were identified. Characteristics and main results of these articles can be found in Table 2.

Table 2

Table 2. Bariatric surgery and anti-obesity medication.

The 25 included studies vary in design. 19 are retrospective studies (13–30), five are randomized, double-blind, placebo-controlled trials (31–35), including one that utilized a two-way crossover design (31) and one prospective cohort study (36). The types of bariatric surgeries in these trials also varied. The most common procedure is RYGB (13, 15–29, 31, 32, 34–36), followed by SG (13–15, 17–19, 21–30, 34–36), and gastric banding (13, 16, 18, 19, 22–24, 27–29). Other bariatric procedures include biliopancreatic diversion (BPD) (18, 29), gastric plication (28) and revisional SADI (23).

The AOM investigated across the included studies vary considerably. GLP-1 RAs, particularly liraglutide and semaglutide, were the most frequently prescribed agents (13–15, 19–25, 27, 29–36). Dulaglutide was investigated only in the study by Jirapinyo et al. (23). Three studies investigated the additional effect of the dual GLP1-GIP agonist tirzepatide (14, 17, 30). Other investigated medication include phentermine, either as monotherapy or in combination with topiramate (15, 16, 20, 21, 25, 26, 28). Another study reported on the combination of phentermine with metformin (22). Topiramate as monotherapy was also quite common (15, 18, 21, 25). It is also given in combination with sibutramine (30), metformin, liraglutide, and bupropion (15). The other studies described the results of metformin (15, 20, 25, 26), bupropion and naltrexone as either monotherapy or in combination with each other (15, 20, 25, 28), sibutramine (18), orlistat (18, 21), zonisamide (25) and lorcaserin (15, 20, 25, 28). Two studies compared medication versus new bariatric intervention after weight regain after RYGB or SG (30, 36).

The placebo-controlled studies compared the effectiveness of liraglutide versus placebo in patients with weight regain after RYGB (32), patients with poor weight loss response after RYGB or SG (34), or persisted or recurrent type 2 diabetes after RYGB or vertical SG (VSG) (35). In these studies weight loss on liraglutide post RYGB was respectively 8.8% TWL after 12 months (32), 9.49 ± 5.07kg after 6 months (34) and -5.26kg with a confidence interval (CI) ranging from -6.15 to -4.38 kg after 6 months.

One study compared liraglutide to placebo six weeks after conversion RYGB (cRYGB). After 12 months, this trial demonstrated a %TWL of 24.15 ± 2.35 on cRYGB in combination with liraglutide versus 22.70 ± 2.13 on cRYGB with placebo (33). The double-blind, two-way crossover trial compared the combination of transoral outlet obstruction endoscopy (TORe) with liraglutide or placebo in patients with weight regain after RYGB. TORe utilizes an endoscopic suturing or plication device to reduce the diameter of the gastrojejunal anastomosis and/or the gastric pouch, thereby emulating the anatomical modifications achieved through surgical revision (20). The intervention of saline and liraglutide switched after 12 months. After 12 months the liraglutide and TORe group lost 21.69 ± 1.64%TWL while the placebo group lost 14.37 ± 2.58. After 24 months, when all participants have had both 12 months of placebo and 12 months of liraglutide, the group that started with liraglutide had 15.74 ± 5.84%TWL while the other group lost 11.04 ± 4.36%TWL (31).

Adverse events were reported in all five randomized controlled trials. Patients in the liraglutide group experienced more adverse events than those in the placebo group. The most commonly reported side effects were gastrointestinal in nature, with nausea, diarrhea, and constipation being the most frequently observed (31–35).

The prospective cohort study investigated the difference in weight loss between AOM and a novel bariatric intervention. These interventions were split among patients who had undergone a RYGB at least six years prior and had subsequently regained more than 10% of their weight after reaching their nadir. The interventions compared were liraglutide, endoscopic surgery, and resizing of the RYGB pouch using a Fobi ring. After 24 months, patients treated with liraglutide experienced a weight loss of 13 ± 8 kg. Those who received a Fobi ring lost 17 ± 7 kg, while patients who underwent endoscopic surgery lost 3 ± 3 kg (36).

Another study compared weight loss outcomes in patients with a history of SG that, due to weight regain, were treated with either semaglutide, tirzepatide, or a revisional ESG (rESG). After 24 months, the %TWL was 9.2 ± 7 in the group treated with AOM, compared to 13.4 ± 3.7 in the group that underwent rESG (30).

The retrospective cohort studies have investigated the effects of various AOMs after bariatric surgery when administered in cases of weight regain or insufficient weight loss following RYGB, SG and adjustable gastric banding (AGB). Several of these studies have reported the weight-related outcomes per medication. Semaglutide, for instance, was evaluated in the study by Medhati et al., which demonstrated a %TWL of 13.6 ± 10.3 following RYGB and 11.4 ± 9.8 following SG after one year of treatment. Jamal et al. reported a percentage weight change of −10.3 ± 5 after six months of use in individuals with a history of SG. Murvelashvili found an average %TWL of 12.92 ± 1.17 after one year of semaglutide use, with greater efficacy in RYGB patients (15.83 ± 2.48) compared to those with SG (12.36 ± 1.8) or AGB (8.64 ± 2.53).

Liraglutide was investigated by Murvelashvili et al., who found a mean %TWL of 8.77 ± 1.23 after 12 months, with no significant differences between RYGB, SG, or AGB. Muratori et al. reported a BMI reduction of 5.0 ± 6.4 in RYGB patients, 7.6 ± 5.8 in those with LGB, and 5.6 ± 6.9 in patients with an SG. Elhag et al. compared liraglutide use following primary versus revisional bariatric procedures, reporting a %TWL of 7.04 ± 7.53 after one year in the primary group and 5.08 ± 9.05 in the revisional group. Wharton et al. reported a percentage weight change after one year of liraglutide in patients with an RYGB of -6.6 ± 7.1, in patients with an AGB of -4.9 ± 5.6, and in patients with SG of -3.6 ± 3.0. Rye et al. found a mean weight loss of 9.7% (IQR 7.8–13.9%) after 28 weeks of liraglutide treatment. Gorgojo-Martínez et al. reported a reduction in body weight from 106.0 ± 7.2 kg to 102.6 ± 6.9 kg after 24 months of liraglutide therapy.

Non-specified GLP-1 RAs were examined by Edgerton et al., who found a %TWL of 7.7 ± 6.0 after an undefined treatment duration. Tirzepatide was mentioned in the study by Stoll et al., showing a 12.0 ± 3.4% weight reduction after six months. Jamal et al. reported a weight change of −15.5 ± 6.3% after six months in patients with prior SG. Topiramate was investigated by Boger et al., who reported a weight loss of 3.2 kg after 24 months. Toth et al. found a %TWL of 7.2 after 12 months of use. The combination of topiramate/sibutramine was studied by Boger et al., reporting a weight loss of 6.1 kg after 24 months. The phentermine/topiramate combination was evaluated by Edgerton et al., who found a %TWL of 9.8 ± 5.6 after an undefined period. Schwartz et al. reported an excess weight loss (EWL) of 2.8 (CI 1.08–6.54) after 90 days. Phentermine alone was studied by Edgerton et al., showing a %TWL of 4.5 ± 3.7 after an undefined treatment duration. Toth et al. found a %TWL of −7.7 after 12 months, while Schwartz et al. reported an EWL of 6.3 (CI 4.25–8.44) after 90 days. Orlistat was investigated by Boger et al., who reported a TWL of 2.7 kg after six months. When used in combination therapy, it resulted in a weight reduction of 3.9 kg. Metformin was studied by Toth et al., who found a %TWL of 2.9 after 12 months of treatment.

Dharmaratnam et al. investigated if there was a difference in the effectiveness of orlistat, phentermine, liraglutide, topiramate as monotherapy or in combination with each other in patients with insufficient weight loss, weight regain <10% or weight regain ≥10%. They found a %TWL in the insufficient weight loss group of 0.7 ± 4.2, in the weight regain <10% group of 0.7 ± 4.6 and in the weight regain ≥10% group of 1.8 ± 4.3. Stanford et al. and Nor Hanipah et al. investigated the difference in weight loss after starting AOM between RYGB, SG and LGB. The effect of lorcaserin, naltrexone/bupropion, phentermine, phentermine/topiramate and bupropion, metformin, phentermine, topiramate, zonisamide were investigated. After a follow-up of 1 year, Nor Hanipah et al. found a %TWL in patients with a RYGB of 2.8, in patients with SG of 0.3 and in patients with LGB of 4.6. Stanford et al. found a %TWL of 4.3 ± 5.7 in patients with SG and -8.3 ± 8.1 in patients with RYGB.

This overview indicates that AOM after bariatric surgery are primary studied in case of insufficient weight loss or weight regain.

The most commonly investigated AOMs are GLP1-RAs and the dual agonist tirzepatide. These GLP-1 RAs appear to promote clinically meaningful weight loss in patients experiencing weight regain or insufficient weight loss after bariatric surgery. Liraglutide and semaglutide were the most commonly investigated agents, with %TWL outcomes often ranging between 8% and 15%, especially following RYGB (13–15, 19–25, 27, 29–36). Semaglutide and liraglutide demonstrated consistent effects across different surgical types (18, 23, 25, 28, 29, 32, 34, 35).

In contrast, non-GLP-1 RA medications such as phentermine, topiramate, orlistat, and bupropion/naltrexone showed more variable and generally lower weight loss, usually less than 10% TWL (15, 16, 18, 20–22, 25, 26, 28), which is in line with their efficacy in patients without bariatric surgery. Combination therapies outperformed monotherapy in some cases but did not consistently matched the efficacy of GLP-1 RAs (15, 16, 20, 21, 25, 28).

Some studies compared AOM to revisional interventions. While revisional surgeries like pouch resizing or endoscopic procedures often resulted in slightly greater weight loss (30, 33, 36), liraglutide produced comparable outcomes in certain cohorts, suggesting a viable non-surgical alternative, especially for RYGB patients (30, 36).

Most studies were retrospective cohorts and had additional limitations such as heterogeneity in AOM type, dosage, initiation timing and follow-up duration (13–30). Nonetheless, the real-world settings enhance the applicability of the findings. Some studies also noted improvements in metabolic parameters, including HbA1C reductions, reinforcing the dual benefit of GLP-1RAs for weight and glycemic control (29, 35).

Future studies on the use of AOM after bariatric surgery should focus on long-term results, additional health effects and side effects. In addition, the addition of directly AOM after bariatric surgery in those with very high initial body weight or severe comorbidity should also be investigated.

Bariatric surgery and probiotics

We identified six articles that investigated the use of prebiotics in combination with bariatric surgery and that reported weight loss outcomes. Characteristics and results of these articles can be found in Table 3. Several other clinical studies and randomized controlled trials investigated effects other than weight loss of probiotics after bariatric surgery. These studies are not included in this narrative review.

Table 3

Table 3. Gastric surgery and probiotics.

The six studies included in this review had a similar design, all were randomized controlled trials. These trials involved a combined population of 410 patients, of whom 205 received a probiotic intervention (37–42).

Five of the studies compared probiotics to placebo (37–39, 41, 42), while one study investigated prebiotics versus conventional yogurt (40). In two studies, treatment with probiotics or placebo was initiated prior to bariatric surgery (38, 41). In three studies, the intervention commenced after surgery (37, 39, 40), whereas one study did not specify the timing of the intervention (42).

The most common surgical procedure among the included trials was RYGB (37, 39, 40), followed by one anastomosis gastric bypass (OAGB) (38, 41) and SG (38, 42).

The follow-up duration ranged from 12 weeks to six months. Four studies reported %EWL as the primary outcome. In the probiotics groups, %EWL ranged from 61.2 ± 14.1 to 46.8 ± 12.7, while in the placebo groups it ranged from 64.0 ± 12.4 to 36.3 ± 12.7. One study reported %TWL, which was 30.4 ± 11.5 in the probiotics group and 26.5 ± 8.8 in the placebo group after six months. The final study reported total weight loss in kilograms, with a loss of 35.3 ± 3.2 kg in the probiotics group and 35.5 ± 3.0 kg in the placebo group.

None of the reviewed trials found a statistically significant difference in weight loss between the probiotics and placebo groups. Although these findings suggest that probiotic supplementation, whether initiated before or after bariatric surgery, does not significantly affect total weight loss, a systematic review of four trials by Zhang et al. reported that probiotic intake at the time of bariatric surgery may have a beneficial effect on waist circumference (43).

Potrykus et al. evaluated besides weight loss also the effect on glycemic control, lipid profiles, liver enzyme levels, iron status, and vitamin levels. Across all the parameters, no significant differences were identified between the probiotic and placebo groups (38).

A systematic review examined the effects of probiotics and synbiotics on small intestinal bacterial overgrowth (SIBO) and other gastrointestinal symptoms (GIS). This review included five studies with a combined total of 396 patients and follow-up durations ranging from two weeks to six months. Pooled meta-analysis revealed no significant differences between probiotics, synbiotics, and placebo in alleviating SIBO or GIS symptoms (44). Although gastrointestinal complaints are common following bariatric procedures and may be influenced by microbial dysbiosis, current evidence does not support the efficacy of microbial supplementation in this context. The variability in probiotic strains, dosages, treatment durations, and diagnostic criteria for SIBO across studies may have contributed to these equivocal results (44).

A prospective randomized trial assessed the incidence of gallstone formation following SG or OAGB in patients receiving probiotics, digestive enzymes, or ursodeoxycholic acid (UDCA). These interventions commenced three days postoperatively and were continued for six months. After six months, fewer gallstones or biliary sludge were observed in the groups receiving UDCA or probiotics compared to the group receiving digestive enzymes; however, this difference did not reach statistical significance (45). This indicates that the study was underpowered, since the efficacy of UDCA to prevent gallstone formation after bariatric surgery has been demonstrated repeatedly (46). An adequately powered study should be performed to evaluate the potential of probiotics for the prevention of gallstones.

Additionally, a study explored whether the addition of prebiotics to the diet of postmenopausal women who had undergone RYGB could enhance calcium absorption. No significant differences were found between the prebiotic and placebo groups. The wide confidence intervals suggest a potentially variable effect of short-chain fermentable fiber (SCF) across this population (47). Again, the small sample size precludes clear conclusions and an adequately powered study is warranted.

Overall, the studies did not show a consistent meaningful effect of probiotics and prebiotics on weight loss after bariatric surgery. The effect on metabolic parameters was also limited. The small sample sizes of the studies and heterogeneity in interventions makes it impossible to draw strong conclusions. Two systematic reviews came to similar conclusions (43, 48).

While the meta-analysis from Zhang et al. (43) identified statistically significant reduction in waist circumference at 12 months of -4.21 cm in favor of the probiotics group, the meta-analysis of Wang et al. (48) did not found a statically significant difference. It did however found a statistically significant difference in weight and BMI in favor of the probiotics group, this was however not found by the first meta-analysis. Similarly, Wang et al. (48) observed a small but statistically significant differences the liver enzyme aspartate aminotransferase and vitamin B12 levels in favor of probiotic use. These effects however, were modest in magnitude and did not extend to other related markers, including alanine aminotransferase, Gamma-GT, or additional micronutrients.

In this review we discuss interventions targeting gut microbiome separately. However, we should realize that both bariatric surgery and several AOM such as GLP1-RAs and metformin do have clear influences on gut microbiome composition and related metabolites. These alterations may contribute to the observed effects of bariatric surgery and AOM.

Bariatric surgery and GLP-1 receptor agonists induce significant changes in gut microbiota, often increasing beneficial bacteria such as Akkermansia muciniphila, short-chain fatty-acid-producing Bacteria, and other taxa linked to improved metabolic outcomes, while reducing pro-inflammatory species. Although responses vary across individuals, studies and specific treatments, bariatric surgery is generally considered to have a positive effect on gut microbiota (49).

Liraglutide promotes genera linked to improved metabolism, and dulaglutide and semaglutide produce distinct changes in specific beneficial taxa and microbial diversity. These alterations may support long-term metabolic health, aid diabetes management, and help maintain healthy body weight (50). Due to the heterogeneity in probiotic strains used, variations in the timing of interventions, and the short follow-up periods, it is challenging to draw definitive conclusions in regards to weight loss.

Clinical considerations

Although current evidence suggests that GLP-1 RAs and other AOMs can enhance weight loss after bariatric or endoscopic procedures, several clinically relevant issues remain unresolved. Data on weight trajectories after cessation of AOMs in patients post-bariatric surgery are lacking; however, extrapolation from non-surgical obesity trials suggests substantial weight regain after discontinuation, indicating that chronic treatment may be required to maintain weight loss (51).

The implications of prolonged AOM use in patients who have undergone bariatric surgery are insufficiently studied. Most available studies evaluate outcomes over relatively short follow-up periods, whereas obesity is a chronic disease that may necessitate sustained pharmacological therapy. If ongoing treatment is required, this raises important questions regarding long-term safety, tolerability, adherence, and cost-effectiveness in a post-bariatric population, particularly given the altered gastrointestinal anatomy and potential differences in drug absorption. At present, these considerations remain largely unaddressed in the existing literature.

In addition, differences between outcomes reported in clinical trials and those observed in routine clinical practice warrant attention. RCTs typically involve carefully selected patient populations, standardized dosing protocols, and intensive follow-up, which may not reflect real-world settings where access to medication, reimbursement policies, long-term adherence, and follow-up intensity vary considerably. Furthermore, most real-world studies are retrospective and heterogeneous in terms of patient selection, timing of treatment initiation, and choice of pharmacotherapy, limiting direct comparisons and generalizability.

Taken together, these unresolved issues highlight the need for prospective studies with longer follow-up to better define the durability of weight loss, optimal timing of treatment initiation, and the long-term role of AOM after bariatric or endoscopic interventions. Such studies are essential to guide personalized, evidence-based treatment strategies in everyday clinical practice.

Conclusion

Available evidence suggests that combining endoscopic interventions with AOMs, particularly GLP-1RAs, is associated with greater and more clinically significant weight loss than ESG alone. Reported outcomes indicate that adjunctive AOM following ESG improves weight loss outcomes from 15 –21% TWL with ESG alone to 17 – 25% TWL when combined with GLP-1 RAs (9–12). However, ESG combined with other AOMs does not result in significantly greater weight loss than ESG alone (12).

In patients with insufficient weight loss or weight regain after bariatric surgery, GLP-1RAs and the dual GIP/GLP-1RA tirzepatide are associated with clinically meaningful weight loss. With a TWL between 8-15% in the GLP-1RA group (13–15, 19–25, 27, 29–36) and a TWL between 12-15% with the use of tirzepatide (14, 17, 30). By contrast, non-GLP-1 medications typically results in less than 8% TWL and demonstrate more modest and variable effects (15, 16, 18, 20, 21, 25, 26, 28).

Probiotic supplementation during or shortly after bariatric surgery has not demonstrated consistent or clinically relevant effects on postoperative weight loss, and no specific strain or patient subgroup has been identified as clearly beneficial. However, due to the small sample sizes, short follow-up periods and heterogeneity in interventions it is not possible to draw definite conclusions (37–42).

Overall, current evidence suggests thatGLP-1RAs appear to be the most effective AOM in combination with ESG to optimize weight loss. It also appears to be the most valuable for patients with insufficient weight loss or weight regain after bariatric surgery, whereas the role of other AOMs and probiotics remains uncertain.

However, long-term results of AOM use after bariatric or endoscopic procedures is insufficiently studied. Data on weight changes after discontinuation of AOM is lacking. As obesity is a chronic disease, sustained or long-term AOM treatment may be required to maintain weight loss, raising questions regarding long-term safety, adherence, cost and real world feasibility in post-bariatric populations. Further research should prioritize these questions.

Due to the heterogeneity of the topic and the limited number of existing studies, we opted to conduct a narrative review rather than a systematic review. The variability in the available literature, combined with the scarcity of rigorous research, makes it challenging to synthesize findings through a systematic approach. A narrative review enables a more flexible and comprehensive examination of the subject, acknowledging both its complexity and the gaps in the current evidence base. Therefore, this approach enables a broader discussion of the topic, while highlighting areas for future research.

Author contributions

JdW: Writing – original draft, Writing – review & editing, Conceptualization, Methodology. MN: Supervision, Writing – review & editing. VG: Writing – review & editing, Conceptualization, Investigation, Methodology, Supervision.

Funding

The author(s) declared that financial support was received for this work and/or its publication. MN is supported by a personal NWO VICI grant 2020 (09150182010020) and an ERC Advanced Grant (101141346) as well as, a NNF MICROBIOME HEALTH INITIATIVE consortium grant NNF24SA0092455 (on which JdW is appointed).

Conflict of interest

Author MN is co-founder and member of the Scientific Advisory Board of Caelus Pharmaceuticals and Advanced Microbiota Therapeutics, the Netherlands. None of these are directly relevant to the current paper. There are no patents, products in development or marketed products to declare.

The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Abbreviations

AGB, Adjustable gastric banding; AOM, Anti-obesity medicine; BPD, biliopancreatic diversion; cRYGB, Conversional Roux-en-Y gastric bypass; ESG, Endoscopic sleeve gastroplasty; EGR, Endoscopic gastric remodeling; EWL, Excess weight loss; GIP, Glucose-dependent insulinotropic polypeptide; GLP1, Glucagon-like peptide-1; LGB, Laparoscopic gastric banding; IWL, Insufficient weight loss; OAGB, One anastomosis gastric bypass; RYGB, Roux-en-Y gastric bypass; SADI, Single anastomosis duodeno-ileal bypass; SG, Sleeve gastrectomy; TORe, Transoral outlet obstruction endoscopy; TWL, Total body weight loss; VBG, Vertical banded gastroplasty; VSG, Vertical sleeve gastroplasty; WR, Weight regain.

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