Comparing Safety and Efficacy Outcomes of Gastric Bypass and Sleeve Gastrectomy in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Sleeve Gastrectomy (SG) could be done by the removal of a big portion of the stomach, leading to reduced amounts of food taken as a result of the smaller stomach size. In contrast, Roux-en-Y Gastric Bypass (RYGB) can be done by creating a small stomach pouch and rerouting a part of the small intestine, employing combined mechanisms of restriction and malabsorption to limit food intake and modify nutrient absorption. Our aim is to identify the most effective and safest surgical intervention for individuals with both Type 2 Diabetes Mellitus (T2DM) and obesity, considering both short and long-term outcomes. We will assess participants undergoing either SG or RYGB to determine the optimal surgical approach. We made a thorough search of PubMed, Cochrane Library, Scopus, and Web of Science databases up to November 2023. Our focus was on randomized controlled trials (RCTs) comparing the safety and efficacy of RYGB and SG in T2DM regarding any extractable data. We excluded studies of other designs, such as cohorts, case reports, case series, reviews, in vitro studies, postmortem analyses, and conference abstracts. Utilizing Review Manager 5.4, we performed a meta-analysis, combining risk ratios (RR) with a 95% confidence interval (CI) conducted for binary outcomes, while mean with SD and 95% CI are pooled for the continuous ones. The total number of participants in our study is 4,148 patients. Our analysis indicates superior outcomes in the group undergoing RYGB surgery compared to the SG group (RR = 0.76, 95% (CI) (0.66 to 0.88), P = 0.0002). The pooled data exhibited homogeneity (P = 0.51, I2 = 0%) after employing the leave-one-out method. For the 1-3 year period, six studies involving 332 patients with T2DM yielded non-significant results (RR = 0.83, 95% CI (0.66 to 1.06), P = 0.14) with homogeneity (P = 0.24, I2 = 28%). Conversely, the 5-10 year period, with six studies comprising 728 DM patients, demonstrated significant results (RR = 0.69, 95% CI (0.56 to 0.85), P = 0.14) and homogeneity (P = 0.84, I2 = 0%). In terms of total body weight loss, our findings indicate significantly higher weight loss with RYGB (mean difference (MD) = -6.13, 95% CI (-8.65 to -3.6), P > 0.00001). However, pooled data exhibited considerable heterogeneity (P > 0.00001, I2 = 93%). Subgroup analyses for the 1-3 year period (five studies, 364 DM patients) and 5-10 year period (six studies, 985 DM patients) also revealed significant differences favoring RYGB, with heterogeneity observed in both periods (1-3 years: P > 0.00001, I2 = 95%; 5-10 years: P = 0.001, I2 = 75%). RYGB demonstrated significant long-term improvement in diabetes remission and superior total body weight loss compared to SG. While no notable differences were observed in other efficacy outcomes, safety parameters require further investigation. no significant distinctions were found in any of the safety outcomes: hypertension (HTN), high-density lipoprotein (HDL), hyperlipidemia, fasting blood glucose, vomiting, low-density lipoprotein (LDL), and total cholesterol. Further research is essential to comprehensively assess safety outcomes for both surgical approaches.


Introduction And Background
The worldwide frequency of obesity and diabetes mellitus (DM) is consistently growing [1].More than 39% of adults are overweight according to WHO in 2016 and 13% are obese [2].Each increase in BMI above the usual range is associated with increased mortality, with a BMI above 40 reducing life expectancy by eight to ten years [3].There is an association between Type 2 DM (T2DM) and obesity; As obesity significantly impacts the early development of chronic diseases, including T2DM, cancer, and cardiovascular diseases.Additionally, it can cause functional impairments, frailty, and an increase in hospitalizations [4][5][6].Additionally, obesity increases insulin resistance and affects the body's ability to keep blood sugar levels regulated, contributing to the onset of the disease [7].Both obesity and T2DM have treatments available, but most of them have the opposite effect on each other.Nonetheless, when it comes to treating both conditions effectively, surgical procedures, especially bariatric surgery, are the way to go [8,9].New guidelines are recommended for the safe and effective use of bariatric surgery in a wide variety of populations, including children and adolescents, based on specific criteria [10].
As per the American Society for Metabolic and Bariatric Surgery, Sleeve Gastrectomy (SG) emerged as the predominant bariatric surgical procedure in the U.S. in 2017, representing 59.4% of all such surgeries.Following closely, the second most prevalent method was Roux-en-Y Gastric Bypass (RYGB), comprising 17% of the total bariatric surgeries performed [11].The top two most commonly used bariatric techniques worldwide are considered RYGB and SG [12].In 2016, SG surgery was performed more often than any other type of surgery worldwide [13].
Both procedures made considerable weight loss and remission of obesity-related comorbidities [14].The specific mechanism is not entirely understood, but it is believed that weight loss and a decrease in appetite are achieved by decreasing the size of the stomach.Additionally, the improvement in bile acids is more pronounced in this procedure.Nonetheless, it is crucial to note that only RYGB incorporates duodenal bypass, a distinctive feature believed to augment diabetes remission by triggering the production of incretin hormones [15].The modification of the gastrointestinal anatomy in RYGB, specifically involving the duodenum, is thought to play a role in the observed improvements in diabetes outcomes, possibly through enhanced incretin hormone activity [16][17][18][19].Some researchers suggest that improved insulin sensitivity in the liver, especially in the weeks following surgery, might contribute to the prompt improvement of glucose intolerance [20].While RYGB is acknowledged as the premier metabolic surgery, it is linked with potential complications, including but not limited to marginal ulcers, internal hernias, dumping syndrome, malnutrition, and deficiencies in essential vitamins [21,22].
In reviews, SG had fewer postoperative complications and reoperations, but more reflux symptoms, such as gastroesophageal reflux disease (GERD) and esophagitis, compared to other procedures [23,24].On the other hand, RYGB was superior in secondary outcomes like dyslipidemia and hypertension (HTN) [25,26].The comparison of the two operations regarding their efficacy in improving DM and facilitating weight loss has not yielded any established differences.The current study, therefore, aims to primarily evaluate the mentioned variables for a follow-up duration of up to 10 years.By conducting this study, we aim to identify the most effective and safest surgical intervention for patients who were selected for SG or RYGB with T2DM and obesity in the short and long terms.

Review Methods
The researchers conducted a comprehensive and thorough evaluation of a systematic review and metaanalysis, ensuring that they followed the most up-to-date guidelines and standards set by PRISMA and Cochrane [27,28].

Eligibility Criteria and Study Selection
We compared RYGB and SG in randomized controlled trials (RCTs) for safety and efficacy outcomes in T2DM patients.We eliminated duplicates with EndNote, screened titles and abstracts, and conducted full-text screening for eligible studies.We also searched references for relevant studies.The previous steps were done by two authors, and any conflicts were decided by the last author.We excluded the following designs; cohort, case reports, case series, reviews, editorials, in vitro, postmortem, and conference abstracts.We excluded any other indication of the operations other than DM patients.

Quality and Risk of Bias (ROB)
To evaluate the degree of bias in the studies under consideration, the team used the Cochrane Handbook for Systematic Reviews (version 1).The studies were categorized as having a high, low, or unclear ROB.Any uncertainties were resolved through conversation and consensus with two co-authors.

Data Extraction
From the included trials, two authors extracted general baseline and summary data that included country, study design, study arms, age, sex, weight, BMI, HbA1c, follow-up duration, inclusion criteria, and study conclusions into an Excel sheet.Outcomes were divided into efficacy and safety sections.In efficacy outcomes, we focused on diabetes remission, HbA1c, total body weight loss, BMI, and quality of life (QOL).
On the other hand safety outcomes were fasting glucose level, dyslipidemia, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), HTN, and vomiting.

Analysis
We employed Review Manager 5.4 software for data analysis, using risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on the nature of the data (dichotomous or continuous).Statistical significance was considered at a P-value below 0.05.Heterogeneity was assessed using I-square (I2) and chisquare tests.For homogeneous data (P ≥ 0.1 or I2 < 50%), a fixed-effect model was used, while for heterogeneous data (P < 0.1 or I2 > 50%), a random-effect model was applied.Subgroup analyses were conducted based on follow-up duration.

Literature Search and Study Selection
After conducting an extensive literature search on various search engines, we retrieved 6,331 records.We excluded 196 papers by removing duplicates and further excluded 6293 articles based on title and abstract screening.Out of the remaining 38 articles, we conducted full-text screening and shortlisted 23 RCTs that matched our standards.We included these 23 RCTs in the meta-analysis to obtain evidence, out of which seven were only in narrative form .All the data are shown in Figure 1.

Study Characteristics
We reviewed all RCTs that investigated the effectiveness of two types of weight loss surgeries, SG and RYGB, on 4,148 confirmed T2DM patients across various countries including the USA, Europe, Taiwan, Brazil and New Zealand.The sample size of both the groups varied from 15 to 462 participants.The female population was more prominent than males.The researchers specified the follow-up duration either by a period ranging from one year to ten years on most of the outcomes.The baseline and summary characteristics of all the included RCTs are presented in Table 1.RCT: Randomized controlled trial; T2D: Type 2 diabetes; T2DM: Type 2 diabetes mellitus; SG: Sleeve gastrectomy; RYBG: Roux-en-Y gastric bypass; HbA1c: Glycated hemoglobin; QoL: Quality of life; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; LSG: Laparoscopic sleeve gastrectomy, SR: Systematic review

Quality of the Included Studies
The included RCTs ranged in quality.Two studies were found to have a low ROB in all their characteristics [32,47]; while two others had a low risk in all domains except for the "Other bias" domain [36,45].Only two studies were found to have a high risk in all domains except for two [40,49].Overall, most of the studies had a low risk in terms of random sequence.The next three domains, namely allocation concealment, blinding of participants, and outcome assessment, were mostly categorized as either low or unclear risk.A graph showing the ROB is presented in (Figures 2, 3).Diabetes remission: Our analysis shows that the group who underwent RYGB surgery had better outcomes compared to the SG group (RR=0.76,95% CI (0.66 to 0.88), P= 0.0002).The obtained data were homogenous (P=0.51)after the leave-one-out method was applied .For the 1-3 year period, six studies comprising 332 DM patients showed insignificant results (RR = 0.83, 95% CI (0.66 to 1.06), P value = 0.14) and homogeneity (P=0.24,I2 = 28%).For the 5-10 year period, six studies comprising 728 DM patients showed significant results (RR = 0.69, 95% CI (0.56 to 0.85), P value = 0.14) and homogeneity (P=0.84,I2= 0%) after the use of leave one out method (Figure 4).The data has been presented in numbers and percentages.

Discussion
Our meta-analysis, comprising 23 RCTs, systematically examined the outcomes of RYGB and SG across various follow-up periods: one to three years, three to five years, and over five years.No significance in BMI was observed between the two interventions overall and in individual follow-up periods, except for a marginal significance (p = 0.05) favoring RYGB in the two to three-year interval.For diabetes remission, a pivotal outcome, RYGB demonstrated significant efficacy in the long-term follow-up, ranging from five to ten years, with consistent and homogenous results, positioning RYGB as superior for patients with T2DM.Total body weight loss favored RYGB significantly in all follow-up periods, emphasizing its efficacy for patients requiring substantial weight loss.Efficacy outcomes related to HbA1C and QoL revealed no significance between RYGB and SG.Regarding safety outcomes, HDL exhibited significance only in the three-year period, while HTN occurrence, though non-significant (p = 0.05), warranted further investigation due to limited data in five studies.LDL showed no overall difference, with significance observed only in the one to two-year interval.No other efficacy outcomes, including vomiting and fasting blood glucose, demonstrated statistical significance.In summary, our comprehensive analysis underscores the superiority of RYGB in achieving diabetes remission and total body weight loss over various follow-up periods, with limited differences in other efficacy and safety outcomes while showing superiority for SG at pretension outcomes.Our contribution is deemed significant in advancing the current understanding of T2DM postbariatric surgery, as we have employed consistent definitions.This approach enhances the comparability of studies, allowing for the interpretation of findings across diverse populations with varying inclusion criteria and from different countries.
The most challenging part in estimating the results of RYGB and SG procedures is that these two procedures are long-term surgeries, and maintaining the connection with the patients and following them up for a long period might be difficult and would result in high costs for the RCT, so we can find that most papers would provide long-term safety results.Despite this fact, many RCTs were published concerning RYGB or SG with limited numbers and short follow-up periods, some focused on diabetic patients alone, and others focussed on all patients who are obese.Higher BMI increases the risk of death and complications for diabetic patients; from our findings, both techniques could efficiently reduce the BMI although no significant difference was found between RYGB and SG [52,53].Bariatric surgeons are consistently striving to innovate and devise novel procedures rooted in SG principles.The objective is to streamline surgical techniques, mitigating both the surgical and metabolic risks associated with the procedure, all the while preserving favorable outcomes.About the safety of the procedures, it is notable that no fatalities were found to be linked with either the SG or the RYGB which would add comfort to the patients intending to go through these primary bariatric procedures [54].
Our study has several strengths as we are the updated version of the previous meta-analysis that was previously performed as we have a bigger population and more included RCTs.Additionally, we only included RCTs although most of the studies made about both surgeries were observational we wanted to maintain RCTs as our only source of evidence as the RCTs are the gold standard for evidence.We made three different subgroups to ensure the results are followed up in the short and the long term.Many RCTs were excluded due to the very poor study design and the high risk of bias.We also had several limitations, The high heterogeneity of the data from the included studies may lead to misleading results, and the included patient numbers in each of the included RCTs were not similar, in addition to the inadequacy of trials and patients, which should be taken into consideration while interpreting these data.The majority of our studies were single centers with a low number of participants.We can indicate that future research to focus on performing multicenter studies with long follow-up periods to estimate the long-term outcomes with the lowest heterogeneity among patients by investigating the side effects of both of the techniques.

Conclusions
RYGB demonstrated a notably significant enhancement in diabetes remission for patients with T2DM, particularly in the long-term follow-up, compared to the SG procedure.RYGB also exhibited superior total body weight loss in both short-term and long-term assessments.However, no significant variations were found in other efficacy outcomes between the two procedures.Safety outcomes warrant further investigation due to the lack of data, with HTN being the only parameter with a p-value of 0.05 that is barely significantly lower in SG compared to RYGB.Notably, no significant distinctions were found in HDL, hyperlipidemia, fasting blood glucose, vomiting, LDL, and total cholesterol.Additional research is needed to assess safety outcomes for both surgical approaches comprehensively.The summary of our findings shows the superiority of the gastric bypass without additional side effects which could be used as a guideline for the bariatric surgeons.
following sleeve gastrectomy (SG) and does not present a safer alternative compared to Roux-en-Y gastric bypass (RYGB).However, RYGB is linked to more pronounced episodes of hypoglycemia.theone-year post-surgery mark, gastric bypass demonstrated superiority over sleeve gastrectomy in achieving type 2 diabetes remission, while both procedures exhibited a comparable positive impact on β-cell function.Opting for gastric bypass as the primary bariatric procedure for individuals with obesity and type 2 diabetes has the potential to enhance diabetes management and lower associated societal expenses."

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Despite superior excess weight loss after RYGB, T2D remission rates did not differ significantly between RYGB and SG after 2 years.Long-term followup data are needed to define the role of SG in the treatment of patients with obesity Over the course of this three-year investigation, sleeve gastrectomy (SG) demonstrated comparable beneficial impacts on diabetes and dyslipidemia when compared to Roux-en-Y gastric bypass (RYGB) in Chinese patients with 2024 Elsaigh et al.Cureus 16(1): e52796.DOI 10.7759/cureus.anda BMI falling within the range of 28-35 kg/m2.To validate these findings, further research with longer-term follow-ups and larger sample sizes is essential."The alterations in dietary fiber and protein intake over the course of one year following both surgical procedures, especially after sleeve gastrectomy (SG), were not aligned with existing dietary recommendations.In practical terms, our results indicate that healthcare professionals and individuals undergoing these surgeries should prioritize achieving adequate levels of protein, fiber, and consider vitamin and mineral supplementation, emphasizing the importance of these nutritional elements."Among individuals with morbid obesity, the application of laparoscopic sleeve gastrectomy, as opposed to laparoscopic Roux-en-Y gastric bypass, did not satisfy the criteria for equivalence in percentage excess weight loss after 5 years.While gastric bypass exhibited a higher percentage of excess weight loss compared to sleeve 2024 Elsaigh et al.Cureus 16(1): e52796.DOI 10.7759/cureus.andobesity, a combination of three years of intensive medical therapy with bariatric surgery led to a higher proportion of patients achieving glycemic control compared to those undergoing medical therapy alone.Examination of secondary outcomes, such as body weight, usage of glucose-lowering medications, and quality of life, also indicated favorable outcomes in the surgical groups after three years, in contrast to the group solely receiving medical therapy."

FIGURE 3 :
FIGURE 3: Risk of bias graph