The Role of Preoperative Consumption of Antiobesity Medications in Patients Undergoing Bariatric and Metabolic Surgery

Abstract

Introduction:

Antiobesity medications (AOM) are increasingly popular due to studies showing sustained weight loss. This study evaluated patients prescribed AOMs before bariatric and metabolic surgery (BMS).

Methods:

A retrospective analysis was conducted on patients undergoing BMS from January 2021 to October 2022 at a single tertiary center. Patients who received AOMs preoperatively were compared to a control group.

Results:

This study included 169 patients with BMS: sleeve gastrectomy (n = 29), one anastomosis gastric bypass (n = 102), Roux-en-Y gastric bypass (n = 30), and single anastomosis duodeno-ileostomy (n = 8). Thirty-five patients took AOMs within 1 year before surgery and 134 were in the control group. Baseline characteristics were similar between groups. Body mass index (BMI) did not significantly differ at the first clinic visit or on the day of surgery. However, BMI reduction was significantly higher in the AOM group from the first visit to the day of surgery (1.37 vs. 0.05; p = 0.04). Major complication rates did not differ significantly between groups. At 6, 12, and 18 months of follow-up, readmission rates, BMI, and total weight loss showed no significant differences between groups.

Conclusion:

AOM use prior to BMS is associated with significantly higher weight loss until the day of surgery but shows no significant difference in midterm follow-up.

Introduction

Severe obesity has been a longstanding epidemic, with its rates continuing to increase over the last decades. It is suggested that by 2030, one in two adults in the United States will have obesity.^1,2 Metabolic and bariatric surgery (MBS) is reported to be the most effective treatment for severe obesity. Long-term studies suggest that it is associated with a high rate of sustained weight loss, improvement or remission of obesity-associated medical problems, increased life expectancy, decreased rates of cancer, and decreased rates of mortality.^3–5

The role of antiobesity medications (AOMs) has been documented since the early to mid-20th century, with their development posing challenges over the years. However, since the early 2000s, a major advancement has occurred due to the discovery of molecular mechanisms that control appetite and influence the metabolic profile. This breakthrough has contributed significantly to the development and evolution of new AOMs.⁶ Consequently, in the last decade, several randomized controlled trials have been published, demonstrating a significantly higher rate of weight loss in patients with obesity undergoing AOM treatment compared to those undergoing lifestyle modification alone.^7–9

Based on these studies, it has been suggested to consider recommending AOMs for patients with a body mass index (BMI) >30 kg/m² or over 27 kg/m² if they have an obesity-related medical condition. Moreover, there has been an increase in the rate of patients using AOMs, driven by heightened awareness among clinicians and patients, as well as intensified drug marketing.¹⁰ Several retrospective studies have indicated that preoperative weight loss is linked to a reduction in postoperative complications and may correlate with lower rates of anastomotic/staple line leaks.^11,12

The objective of this study is to assess patients who were taking AOMs before undergoing MBS and to document their perioperative and 1-year outcomes. Our hypothesis is that patients using AOMs prior to surgery will achieve greater weight loss with a lower incidence of perioperative complications.

Materials and Methods

The study employed a retrospective design utilizing a patient database that was prospectively maintained at a single tertiary bariatric center. It included patients who underwent MBS from January 2021 to October 2022.

The study group comprised patients who underwent surgery during this period and had consumed AOMs prior to their procedures. The control group consisted of patients who underwent surgery during the same period but did not consume AOMs at any point.

The patients considered for surgery were those with severe obesity, meeting the American Society of Metabolic and Bariatric Surgery guidelines. This includes individuals with a BMI >40 kg/m² or those with a BMI >35 kg/m² accompanied by at least one related medical condition. Each patient underwent a routine multidisciplinary evaluation and was later approved for MBS by a multidisciplinary committee. Additionally, all patients were strongly encouraged to lose weight prior to the surgery.

The study was approved by the Institutional Review Board and was performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Statistical analysis

Statistical analysis was performed using the IBM SPSS version 27 statistical data editor. Continuous data are expressed as mean values with the corresponding standard deviation. Categorical data are presented as a number (percent). Fischer test and chi-square test were used for categorical data, and the student’s t test was used for continuous data analysis. All p values were derived from two-tailed tests.

Patient data

The baseline characteristics of patients were retrieved from data and included age, gender, BMI on the day of the first clinic visit, BMI on the day of surgery, and previous bariatric procedures. In addition, we retrieved data regarding the use of AOMs prior to surgery, the type of AOMs consumed, the length of treatment (months), and the occurrence of side effects. We also retrieved data regarding obesity-associated medical problems—type 2 diabetes (T2D), hypertension (HTN), gastroesophageal reflux, hyperlipidemia, and metabolic-associated fatty liver disease.

Among the types of MBS that were performed—sleeve gastrectomy (SG), one anastomosis gastric bypass (OAGB), Roux-en-Y gastric bypass (RYGB), and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADi-S). The choice of the MBS procedure was individualized to each patient, and several factors were taken into consideration including age, gender, BMI, primary vs. revisional cases, obesity-related diseases, and compliance. A patient–physician decision is then made regarding the procedure choice. Consumptions of, or the effect of AOMs seen, did not directly impact choosing the surgical procedure. Perioperative data include operative time, hospital length of stay (LOS), 30-day complications, Clavien-Dindo complication grading classification,¹³ reoperations, and readmissions.

Results

In total, 100 69 patients underwent MBS between January 2021 and October 2022. Among these, 134 patients were in the No-AOM group (79.3%), and 35 patients (20.7%) were in the AOM group. The baseline characteristics are shown in Table 1. There was no significant difference between the groups in most baseline characteristics, including gender and BMI, prior to AOM initiation. However, patients in the AOM group were older (45.7 years vs. 37.7 years, p = 0.002), had a higher rate of T2D (40% vs. 19.4%, p = 0.01), had a higher rate of hyperlipidemia (60% vs. 33.5%, p = 0.003), and had a higher rate of obstructive sleep apnea (OSA) (54% vs. 18.6%, p = 0.04).

Table 1.

Patient Baseline Characteristics

	Totaln = 169	No-AOM n = 134	AOMn = 35	p
Age (years)	39.4	37.7	45.7	0.002
Gender (F%)	121 (71.5%)	97 (72.9%)	24 (66.6%)	0.4
BMI at 1^st clinic (SDV)	41.7 [5.3]	41.6 [5.1]	42.3 [5.7]	0.4
BMI after Rx	41.7 [5.4]	41.6 [5.3]	41.8 [5.7]	0.8
BMI point reduction	0.3 [1.45]	0.01 [1.4]	1.37 [0.9]	0.001
T2D	40 (23.6%)	26 (19.4%)	14 (40%)	0.01
Hypertension	56 (33.1%)	40 (29.8%)	16 (45.7%)	0.07
Hyperlipidemia	66 (39%)	45 (33.5%)	21 (60%)	0.003
GERD	68 (40%)	57 (42.5%)	11 (31.4%)	0.23
OSA	44 (26%)	25 (18.6%)	19 (54%)	0.04
MAFLD	139 (82%)	109 (81.3%)	30 (85%)	0.5
Type of bariatric procedure
SG	29 (17%)	21 (15%)	8 (22.8%)	0.3
OAGB	102 (60%)	81 (60.4%)	21 (60%)	0.3
RYGB	30 (17.7%)	25 (18.6%)	5 (14.2%)	0.9
SADI-S	8 (4.7%)	7 (5.2%)	1 (2.8%)	—
Prior bariatric surgery	47 (27.8%)	37 (27.6%)	10 (29.4%)	0.8

AOM, antiobesity medications; BMI, body mass index; GERD, gastroesophageal reflux disease; MAFLD, metabolic-associated fatty liver disease; OAGB, one anastomosis gastric bypass; OSA, obstructive sleep apnea; RYGB, Roux-en-Y Gastric Bypass; SADi-S, single anastomosis duodeno-ileal bypass with sleeve gastrectomy; SG, sleeve gastrectomy; T2D, type 2 diabetes.

The average duration of AOM use prior to surgery was 6.6 months (interquartile range = 7). Nine patients (25.7%) reported experiencing side effects from the medications. The breakdown of AOM use among the patients was as follows:

Fifteen patients (42.8%) received Liraglutide

Eleven patients (31.4%) received Semaglutide

Four patients (11.4%) received both Liraglutide and Semaglutide

Five patients (14.2%) received a different regimen

Twenty-nine patients (17%) underwent SG, 102 patients (60%) underwent OAGB, 30 patients (17.7%) had RYGB, and eight patients (4.7%) underwent SADI-S. Forty-seven patients (27.8%) underwent these procedures as revisional MBS, with 27.6% in the No-AOM group and 29.4% in the AOM group. There was no statistically significant difference in the types of MBS performed between the groups.

The mean BMI at the first clinic appointment, prior to commencing AOM, was not different between the groups (41.4 ± 5 in the No-AOM group vs. 42.3 ± 5.7 in the AOM group, p = 0.4), nor was it different just before surgery (41.6 ± 5.3 in the No-AOM group vs. 41.8 ± 5.7 in the AOM group, p = 0.8). However, the BMI reduction was significantly higher in the AOM group (1.46 vs. 0.01, p = 0.001).

The perioperative outcomes are depicted in Table 2. There was no significant difference between the No-AOM and AOM groups in terms of operative time (92 min vs. 83 min, p = 0.2), LOS (3.8 days vs. 4.8 days, p = 0.12), 30-day complications (14.1% vs. 11.7%, p = 0.6), major complications (Clavien-Dindo grade above 3) (3.7% vs. 5.7%, p = 0.3), and readmissions (9.7% vs. 5.7%, p = 0.2). However, two patients (5.7%) in the AOM group needed a reoperation within 30 days, compared to one patient (0.7%) in the No-AOM group.

Table 2.

Perioperative Outcomes

	Totaln = 169	No-AOMn = 134	AOMn = 35	p
Operation time (min)	90 ± 45.1	92 ± 47	83 ± 36	0.2
LOS	4 ± 3	3.8 ± 2.1	4.8 ± 5.2	0.12
30-day complications	23 (13.6%)	19 (14.1%)	4 (11.7%)	0.6
CD < >3	7 (4.1%)	5 (3.7%)	2 (5.7%)	0.09
Readmission	15 (8.8%)	11 (9.7%)	2 (5.7%)	0.2

AOM, antiobesity medications; CD, Clavian–Dindo score; LOS, length of hospital stay.

Reoperations included surgical drainage for abdominal collections (n = 2) and concomitant empyema (n = 1). One patient required reoperation due to a cystic stump leak in a patient undergoing concomitant cholecystectomy.

Change in BMI over time was assessed in both the No-AOM and AOM groups. At 6 months, 111 patients were available for follow-up in the No-AOM group (65.6%), compared to 34 patients in the AOM group (97.1%). At 12 months, 108 patients from the No-AOM group (64%) and 34 patients from the AOM group (97.1%) were available. After 18 months, 109 patients from the No-AOM group (81.3%) and 32 patients from the AOM group (91.4%) were available for follow-up. The BMI trends are illustrated in Figure 1 and detailed in Table 3. The average BMI at 6 months was 33.3 ± 4.9, at 12 months was 29.1 ± 4.93, and after 18 months was 28.7 ± 6.5. There was no significant difference between the No-AOM and AOM groups in terms of change in BMI during follow-up at all time periods. A subanalysis to compare weight loss outcomes between the AOM group and the No-AOMs with regard to the different types of procedures performed was also formulated (Supplementary Tables S1, S2 and S3), and this did not demonstrate any meaningful differences.

FIG. 1.

BMI trends over time. AOM, antiobesity medications; BMI, body mass index.

Table 3.

BMI Trends over Time

	Totaln = 169	No-AOMn = 134	AOMn = 35	p
BMI at surgery	41.7 [5.4]	41.6 [5.3]	41.8 [5.7]	0.8
BMI after 6 months	33.3 ± 4.9	33 ± 4.9	34.2 ± 4.9	0.2
BMI point reduction at 6 months	8.4	8.6	7.6
BMI after 12 months	29.1 ± 4.93	28.8 ± 5.1	30.1 ± 4.2	0.20
BMI point reduction at 12 months	4.2	4.2	4.1
BMI after 18 months	28.7 ± 6.5	28.6 ± 6.3	29.3 ± 7.2	0.58
BMI point reduction at 18 months	0.4	0.2	0.8

AOM, antiobesity medications; BMI, body mass index.

The resolution of T2D and HTN is shown in Table 4-The number of patients decreased significantly in both groups. Both T2D and HTN prevalence decreased in both groups postoperatively (p < 0.05), the AOM group showed a more substantial reduction (T2D −30.6% in AOM vs. −9.8% in non-AOMs and for HTN-−33.3% in AOM vs. −18.8% in non-AOM).

Table 4.

Resolution of T2D and HTN for Patients Undergoing MBS

	Preoperative	At last follow-up	Change (%)	p
T2DNo-AOM	25/133(18.8%)	12/133(9%)	−9.8%	0.02
T2DAOM	15/36(41.7%)	4/36(11.1%)	−30.6%	0.002
HTNNo-AOM	39/133(29.3%)	14/133(10.5%)	−18.8%	0.0001
HTNAOM	17/36(47.2)	5/3613.9%	−33.3%	0.001

HTN, hypertension; MBS, metabolic and bariatric surgery; T2D, type 2 diabetes mellitus.

Discussion

In this study, we examined the outcomes of patients who were prescribed AOM prior to undergoing MBS. Patients in the AOM group were significantly older and had a higher prevalence of T2D, OSA, and hyperlipidemia compared to the No-AOM group. The change in BMI from the first clinic visit to the day of surgery was significantly higher in the AOM group. However, there were no significant differences in operative time, major complications, or LOS between the two groups. Additionally, at the 18-month follow-up, there was no difference in weight loss outcomes between the groups.

Both Liraglutide and Semaglutide, which are glucagon-like peptide-1 receptor agonists (GLP-1RAs), have a central action with effects on nutrient-stimulated hormones.¹⁴ Originally developed for the treatment of T2D, these medications have been found to effectively reduce both blood glucose levels and body weight.^15,16 The Satiety and Clinical Adiposity—Liraglutide Evidence program consists of four phase 3a clinical trials that investigated the effects of liraglutide on weight loss in individuals with and without diabetes. One randomized controlled trial with a 56-week follow-up period included 3731 patients who were randomly assigned to either lifestyle intervention plus liraglutide (3.0 mg once daily) or lifestyle intervention plus placebo.¹⁷ After 56 weeks, 63.2% of patients in the liraglutide group compared to 27.1% in the placebo group lost at least 5% of their body weight (p < 0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (p < 0.001).

In recent years, several studies have demonstrated the efficacy of AOM compared to lifestyle intervention alone. For example, a study by Wilding et al.⁸ randomized 1961 patients to once weekly semaglutide with lifestyle intervention or placebo with lifestyle intervention. They reported a change in body weight from baseline at week 68 of 14.9% in the AOM group versus 2.4% in the control group (p < 0.001). Another study by Rubino et al.⁹ showed that patients receiving semaglutide and not switched to placebo after 20 weeks had significantly better weight loss outcomes (−7.9% weight loss for semaglutide versus +6.9% for placebo). In our study, we found that patients in the AOM group had a significantly higher reduction in BMI compared to those not receiving AOM. While this reduction was lower than that reported in the aforementioned studies on AOMs, it is important to note that the implementation of AOMs in our country is still in its early stages. The prescription of these medications is not always guided by bariatric surgeons. We believe that a multidisciplinary approach involving the bariatric surgeon could lead to better outcomes, including the prescription of AOMs. Additionally, it’s important to consider that patients in our cohort consumed different medications for varying durations, which could impact the results.

Preoperative weight loss is thought to potentially improve surgical outcomes in various ways. In a study by Van Nieuwenhove et al.,¹⁸ 298 patients were randomly assigned to either a 2-week preoperative very low-calorie diet (VLCD) regimen or no preoperative dietary restriction (control group). The study found no differences between the groups in terms of operating time, estimated blood loss, or intraoperative complications. However, after a 30-day follow-up period, the number of complications was higher in the control group compared to the VLCD group (18 vs. 8; p = 0.04). Alami et al.¹⁹ conducted a study with 100 patients undergoing Roux-en-Y gastric bypass (RYGB) and were randomized into two groups: one with a requirement to achieve a 10% weight loss before surgery and another with no weight loss requirements. The study found that preoperative weight loss was linked to a reduction in operating room time and an improved percentage of excess weight loss in the short term. However, it did not have an impact on major complication rates or conversion rates. In a retrospective analysis by Alvarado et al.²⁰ involving 90 patients with preoperative weight loss ranging from 0% to 23.8% (mean 7.25%), it was found that preoperative weight loss was associated with greater postoperative weight loss at 12 months and shorter operative times with RYGB. However, there was no correlation between preoperative weight loss and postoperative complications or improvement in comorbidities.

In our study, we did not observe a significant difference in perioperative outcomes, including major complications, operative time, LOS, reoperations, and readmissions. However, we believe that this data may not fully reflect the technical challenges that can arise during bariatric surgery, especially in patients with an enlarged liver and increased visceral fat. Despite the lack of difference in outcomes, we still believe that there may be advantages for both the surgeon and the patient when weight loss is achieved prior to surgery.

We encourage our patients to lose weight before surgery, as it serves multiple purposes. First, it allows us to assess their compliance and commitment to the treatment plan. Second, preoperative weight loss may facilitate the surgical procedure and potentially lower perioperative complications. For patients who have struggled to lose weight through lifestyle modifications alone, we recommend considering the use of AOMs before undergoing MBS. Additionally, for patients with a higher BMI (>50 kg/m²), we generally advise combining AOMs with lifestyle modifications to enhance the weight loss effect before surgery. This comprehensive approach aims to optimize outcomes and improve the overall success of the surgical intervention.

We advise patients who have undergone MBS to stop using AOMs for at least 18 months postoperatively. During this period, the effects of MBS typically reach their lowest point. We have successfully followed up with 81.3% of our patients in the No-AOM group and 91.4% of patients in the AOM group within this timeframe, which we consider reasonable and reflective of the typical experience of most surgeons. Despite this, we did not observe significant differences in weight loss outcomes between the two groups. In general, the trend of AOMs increased in our country in the last five years, and its combination with MBS was unclear. Our center’s practice was to evaluate the efficacy of MBS prior to adding AOMs to the patient. This practice has evolved throughout the years, and nowadays the indication for AOMs postoperatively is done in selective cases.

When evaluating the resolution of associated medical problems namely T2D and HTN, patients benefited significantly from the combined effect of surgery and AOM compared to those who underwent surgery alone. Despite the low number of patients, our analysis suggests a potential advantage for patients consuming AOMs prior to surgery, as the AOM group showed a more substantial reduction in the resolution of T2D and HTN.

Our study has several limitations that should be considered. First, it is retrospective in nature, with nonrandomized and nonmatched groups. This design can introduce biases such as underreporting and selection bias. Although the groups were comparable in most aspects, there were differences in age and rates of preoperative T2D and hyperlipidemia, which could affect the results. Second, the study was conducted at a single center, which may limit the generalizability of the findings to other populations or settings. Additionally, patients in the AOM group were prescribed different medications for varying durations, and it was unclear if all patients were fully compliant with their AOM regimen. This lack of uniformity makes it challenging to conduct a subgroup analysis based on specific AOMs or compliance levels.

To address these limitations and provide more robust evidence, further comparative long-term studies with larger cohorts would be beneficial. These studies could help clarify the perioperative outcomes associated with preoperative AOM use and provide more insight into its effectiveness and safety profile.

Despite the limitations mentioned, our study also has several strengths. It includes a relatively large cohort of patients from a single center, where a standardized approach to care was followed. The study also benefits from a relatively long follow-up period of 18 months, allowing for a more comprehensive assessment of outcomes.

Furthermore, despite the older age of patients in the AOM group, we did not observe any meaningful differences in terms of LOS or perioperative complications compared to the No-AOM group. This suggests that preoperative weight reduction, as seen in the AOM group, may have played a role in mitigating these factors. We believe that recommending preoperative weight loss can play a beneficial role and provide valuable insights for both the medical team and patients. First, preoperative weight loss may help reduce the liver size, facilitating MBS by providing more working space and potentially shortening operative times. This could lead to fewer complications, LOS, and hopefully reduce the need for readmissions and reoperations. Additionally, preoperative weight loss can serve as a tool to assess patients’ compliance and dedication to the weight loss journey. It allows patients to demonstrate their commitment to lifestyle changes, which are crucial for long-term success after MBS.

Conclusion

Based on our findings, AOM treatment prior to MBS does not result in significant differences in operative time, major complications, or LOS. Additionally, at the 18-month follow-up, there was no disparity in weight loss outcomes between patients who received AOM treatment and those who did not. As the use of AOMs becomes more common, there is a need for a prospective randomized trial to explore the potential benefits of preoperative weight loss induced by AOM before bariatric surgery. Such a study could provide more definitive evidence regarding the efficacy and safety of this approach.

Footnotes

Authors’ Contributions

Y.L.: Study concept and design, data analysis and compilation, revision of the article, writing of the article, and approval; N.D.: Data acquisition; F.K.: Data acquisition; S.M.E.: Revision of the article and approval; A.K.: Revision of the article and approval; G.L.: Revision of the article and approval; and A.A-A.: Study concept and design, data analysis and compilation, revision of the article, writing of the article, and approval.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

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Supplementary Material

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