Bariatric Surgery and Glucagon-Like Receptor-1 Agonists' Effects on Weight, HbA1c and Cardiovascular Outcomes: A Meta-Analysis

Obesity is on the rise globally and is considered a chronic epidemic; the rising rates of obesity together with its comorbidities significantly impact the patient's quality of life and rising healthcare costs [1]. The aetiology is complex and involves genetic predisposition and unhealthy lifestyles in terms of lack of physical exercise and consumption of high-calorie foods [2]. The prevalence of obesity is 12.5% globally.

In the year 2022, 890 million people were obese and 2.5 billion were overweight (16% and 43% of the adult population, respectively). The projection for the year 2035 is 53% [3]. The obesity-associated mortality is high and obesity caused 3.7 million deaths in the year 2021, mainly due to cardiovascular and neurological disease, diabetes mellitus, chronic respiratory disease and obesity-related cancers [4].

Obesity management is challenging: Lifestyle effects are modest and short-term; in addition, most patients are non-adherent to lifestyle recommendations. Physical exercise, behavioural therapy and reduction of calorie intake are recommended as first line, but the maintenance of weight loss is challenging despite continuous monitoring and counselling [5]. Early drug therapies have low efficacy and safety concerns, including cardiac and psychiatric adverse events [6]. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are introduced as antidiabetic medications and have shown high efficacy in weight reduction and glycaemic control. Tirzepatide is a GLP-1agonist and glucose-dependent insulinotropic polypeptide (GIP) with different combination receptor binding affinity and molecular structure [7,8]. These medications were approved for diabetes in 2014 and later approved for weight reduction and showed cardiovascular risk reduction [9].

Bariatric surgery has been performed as an effective treatment for obesity and related comorbidities. However, the uptake is low and amounts to 0.01% of the world’s population according to 2013 reports [10]. Bariatric surgery and GLP-1 agonists have the potential to curb obesity with good cardiovascular outcomes. GLP-1 agonists are paradigm shift in obesity trends and shifted the bariatric surgery to the sideway track, Dawwas et al. [8] conducted a study in the USA and showed 65% reduction in bariatric surgery following the approval of GLP-1 agonists, a plausible explanation could be the significant surge in GLP-1 agonist surge. The above observations supported Lin et al. [11] findings, other contributing factors for bariatric surgery reduction could be limited insurance coverage [12] and referral system [13]. Bariatric surgery might outperform GLP-1s in cardiovascular outcomes beyond weight loss because of high cost and gastrointestinal side effects that can lead to treatment cessation and weight regain [11]. The American Academy of Paediatrics Clinical Practice Guidelines endorsed bariatric surgery as an effective/safe treatment of obesity in adolescents in alignment with a 15% increase in bariatric surgery in this age group [14,15].

GLP-1 agonists are effective in weight reduction after regain following bariatric surgery [16,17]. In addition, GLP-1 agonists were effective adjuvant therapy for preoperative weight loss before bariatric surgery [18]. However, studies comparing bariatric surgery and GLP-1 agonists are limited by a small sample of the included studies and do not include all obesity comorbidities [19-22].

Objectives

We aimed to compare bariatric surgery and GLP-1 agonists in weight reduction, effects on HbA1c and cardiovascular outcomes.

We conducted this meta-analysis in August and September 2025 and we strictly followed the PRISMA Guidelines.

Inclusion Criteria

Prospective, retrospective, clinical trials and case-control studies must compare GLP-1 agonists and bariatric surgery outcomes. However, we included only retrospective studies.

Exclusion Criteria

Commentaries, grey literature, opinions, letters to the Editors, case reports and study protocols were excluded.

Population

All patients with obesity/diabetes who received GLP-1 agonists in comparison with bariatric surgery.

Intervention

Different bariatric surgery procedures and GLP-1 agonists.

Outcome Measures

The outcome measures were the effect of bariatric surgery on body mass index, HbA1c, heart failure and major cardiovascular adverse events (MACE). MACE is defined as nonfatal stroke, non-fatal myocardial infarction and cardiovascular death.

Literature Search

We systematically searched PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science for relevant articles that assessed the effects of bariatric surgery and GLP-1 agonists on HbA1c, body mass index and MACE. The keywords used were bariatric surgery, sleeve gastrectomy, gastric bypass, gastric banding, GLP-1 agonists, GIP agonists, semaglutide, tirzepatide and liraglutide, MACE, acute coronary syndrome, myocardial infarction and stroke with Boolean ^"AND^" and ^"OR^". Out of the 1142 articles retrieved, 716 remained after duplication removal, of them, 22 full texts were reviewed and 7 full texts were included in the final meta-analysis.

Data Extraction

The first author's name, year of publication, country, study type, study duration, number of participants in bariatric surgery and GLP-1 agonists and body mass index were entered in an Excel sheet. Figure 1 and tables 1 and 2.

Type of Surgery and GLP-1 Agonists

The type of bariatric surgery differs widely and included Sleeve gastrectomy, gastric bypass, banding and the GLP-1 agonists used were Liraglutide, Exenatide, Lixisenatide, dulaglutide and semaglutide.

Figure 1: Literature search showing a comparison between bariatric surgery and GLP-1 agonists regarding the effects on HbA1c and cardiovascular outcomes (The PRISMA Chart)

Table 1: Basic characteristics of the included studies

Table 2: Body mass index, HbA1c and major cardiovascular adverse events in patients who received bariatric surgery and glucagon receptor-1 agonists

MACE: Major adverse cardiovascular events GLP-1 agonists: Glucagon like receptor-1 agonists BMI: Body mass index

Table 3: The risk of bias of the retrospective studies (Newcastle Ottawa Scale)

Table 4: Analysis of the quality of evidence by Grading of Recommendations Assessment, Development and Evaluation (GRADE)

Figure 2: Body mass index in bariatric surgery and GLP-1 agonists

Figure 3: HbA1c in bariatric surgery and GLP-1 agonists

Figure 4: HbA1c in bariatric surgery and GLP-1 agonists

Quality Assessment of the Included Studies

The quality of the included studies was assessed using the Newcastle Ottawa Scale (17, all studies showed good quality except one) (Table 3).

Statistical Analysis

We used the Cochrane tool for meta-analysis (RevMan, version 5.4, Oxford, United Kingdom) for data analysis, the dichotomous and continuous data were entered and the data were analysed, odds ratio and standard differences were estimated at 95% confidence interval, the heterogeneity was assessed and considered significant when I² was 50% and the random effect was used, the fixed effect was used for I² <25%. Forest plots and funnel plots were generated, the Chi-Square test was assessed with mean differences and Z Scores. A subgroup analysis was conducted to eliminate studies with high contribution to heterogeneity. A p-value <0.05 was considered significant.

The Quality of Evidence

The quality of evidence is very low as shown in table 4.

Characteristics of the Included Studies

We included seven studies [9,10,23-27] (all retrospective) and 259338 patients, three were published Europe, one in the USA and three were conducted in Asia 52.5% to 74% were women and their ages ranged from 47 ±8 to 56 ± 9 years, the duration of the trials ranged from 1 to 12.9 years, the BMI ranged from 34.90±0.21 to 44±7KG/m2 and the HbA1c ranged from 6.24±1.18 to 9.1±1.7. Liraglutide was the most commonly used GLP-1 agonist and Roux-en-Y gastric bypass or sleeve gastrectomy were the most commonly used bariatric surgeries (Tables 1 and 2).

In the present meta-analysis, 5 studies compared the BMI of bariatric surgery and GLP-1 agonists [9, 23-26]; bariatric surgery reduced BMI more than GLP-1 agonists, Z=2.67, Standard mean difference (SMD), -8.23, 95% CI, -11.02-5.45 and P-value <0.001 and the standard difference=4. However, a significant heterogeneity was found, Chi-square, 8603.53, I2 for heterogeneity=100% and P-value for heterogeneity <0.001 (Figure 2).

Bariatric surgery and GLP-1 achieved similar reduction in the HbA1c [9, 24. 25], Z=0.29, MD, 0.08, 95% CI, -0.45-0.6 and P-value, 0.77 and the standard difference=2. However, a significant heterogeneity was found, Chi-square, 237.63, I2 for heterogeneity=99% and P-value for heterogeneity <0.001 (Figure 3). A subgroup analysis was conducted after removing the study with significant heterogeneity in which the HbA1c reduction was more in bariatric surgery, Z=26.96, MD, -0.35, 95% CI, -0.37--0.32 and P-value <0.001 and the standard difference=1. No significant heterogeneity was found, Chi-square, 1.04, I2 for heterogeneity=4% and P-value for heterogeneity, 0.31. Figure 4.

Bariatric surgery showed less MACE compared to GLP-1 agonists [9,10,24,27], Z=2.83, odds ratio, 1.50, 95% CI, 1.13-1.98 and P-value, 0.005 and the standard difference=3. However, a significant heterogeneity was found, Chi-square, 30.14, I2 for heterogeneity=90% and P-value for heterogeneity <0.001, MACE remained lower after removing the study with high contribution to heterogeneity, Z = 3.84, odds ratio, 1.34, 95% CI, 1.15-1.56 and P-value, 0.0001 and the standard difference=2. No significant heterogeneity was found, Chi-square, 2.51, I² for heterogeneity =20% and P-value for heterogeneity, 0.28 (Figure 5 and 6).

Figure 5: Major adverse cardiovascular events in bariatric surgery and GLP-1 agonists

Figure 6: Major adverse cardiovascular events in bariatric surgery and GLP-1 agonists after removing Adekolu et al. [27]

Figure 7: Heart failure in bariatric surgery and GLP-1 agonists

Similarly, heart failure was lower in bariatric surgery group, Z = 4.89, odds ratio, 1.87, 95 % CI, 1.46-2.40 and P-value <0.001 and the standard difference =1, no significant heterogeneity was found, Chi-square, 1.52, I2 for heterogeneity =34% and P-value for heterogeneity, 0.22 (Figure 7).

In this meta-analysis, Bariatric surgery reduced the BMI more than GLP-1 agonists, Standard mean difference (SMD), -8.23, 95% CI, -11.02-5.45, with no differences regarding the HbA1c, MD, 0.08, 95% CI, -0.45-0.6. However, HbA1c was lower in bariatric surgery after eliminating heterogeneity, MD, -0.35, 95% CI, -0.37--0.32. The MACE was lower in bariatric surgery compared to GLP-1 agonists, odds ratio, 1.50, 95% CI, 1.13-1.98 (the result was similar after eliminating heterogeneity, odds ratio, 1.34, 95% CI, 1.15-1.56) and heart failure was lower in bariatric surgery compared to GLP-1 agonists, odds ratio, 1.87, 95% CI, 1.46-2.40. Our findings were similar to those of Sarma et al. [19], who conducted a meta-analysis and found higher weight reduction in the bariatric surgery group compared to GLP-1 agonists. Sarma et al. [19] found higher HbA1c in bariatric surgery; we found a comparable effect of bariatric surgery and GLP-1 agonists on HbA1c. Importantly, we found lower HbA1c in bariatric surgery after removing studies with significant heterogeneity. The contradiction could be explained by the fact that Sarma and colleagues included studies comparing bariatric surgery and medical therapies, including GLP-1 agonists and used studies published by the same authors. Other limitations of their meta-analysis are the inclusion of studies with very small sample sizes [28]. Another study evaluated the outcomes among patients with diabetic nephropathy [29]. Our study supported the findings of Saeed et al. [20], who found lower MACE in patients with bariatric surgery in comparison to GLP-1 agonists. Our findings showed that bariatric surgery achieved higher cardiovascular protection compared to GLP-1 agonists. The reduction of the MACE could be explained by the reduction in the BMI. The effects of GLP-1 agonists on MACE (stroke, myocardial infarction and cardiovascular/all-cause mortality) are well established. Previous studies showed the superiority of GLP-1 agonists on MACE reduction compared to placebo [30,31]. MACE reduction is a priority in patients with obesity and diabetes and the recommendations are the reduction of MACE risk factors, including good glycaemic control, optimal lipid targets and blood pressure control. However, despite the lifestyle modifications and medication use, many of the patients are not meeting the recommended targets, resulting in high morbidity, mortality and healthcare costs [32,33]. The current findings showed that bariatric surgery lowered BMI and MACE compared to GLP-1 agonists; our results imply that physicians may need to consider bariatric surgery for patients with high BMI and cardiovascular risk factors.

A meta-analysis published by Pipek et al. [21] observed the superiority of bariatric surgery compared to drug therapy in line with the current observations, but they compared pharmacological treatment to bariatric surgery and not GLP-1 agonists. In this study, we found lower heart failure in bariatric surgery than in GLP-1 agonists. Our findings were in line with a recent study published in the USA and showed lower rates of heart failure in patients on bariatric surgery compared to semaglutide [34]. Heart failure is common in patients with obesity (852.84 per 10,000), particularly heart failure with preserved ejection fraction and constitutes a clinical and economic burden [35]. Bariatric surgery could be an effective strategy to reduce weight and prevent MACE and heart failure. However, the clinical picture is not complete unless the complications and costs are investigated. Brosnihan et al. [36] stated that GLP-1 agonists are inferior to bariatric surgery in weight management due to adverse events necessitating discontinuation, high cost and lack of insurance coverage and Haseeb et al. [37] showed that sleeve gastrectomy is cost-saving compared to semaglutide. The current study's strength is that it includes the largest up-to-date studies and assesses many outcomes. Our results showed that bariatric surgery is more effective in BMI, MACE and heart failure reduction, with a similar effect on HbA1c.

Bariatric surgery showed better effect on body weight, MACE and heart failure reduction, with similar effects on the glycated haemoglobin. A proper randomized controlled trial comparing surgery vs. GLP-1s recommended. Future research should include cost, safety and patient quality-of-life data and avoid grouping all GLP-1s and surgery types together because they differ significantly.

Limitations

This meta-analysis is limited by including only retrospective studies and the high heterogeneity observed. In addition, we pooled different forms of bariatric surgery and GLP-1 agonists and we could not compare bariatric surgery with the most potent long-acting GLP-1 agonists. A major limitation of this study is that it was conducted by a single author increasing the bias, in addition, we could not compare the side effects and the quality of life that significantly impact the patients care.

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