Efficacy of Metabolic and Bariatric Surgery Compared with GLP-1 Receptor Agonist Treatment in Preventing Mortality and Major Adverse Cardiac Events Among Individuals with Obesity and Type 2 Diabetes: A Systematic Review and Meta-analysis

Abstract

Introduction

Obesity and type 2 diabetes mellitus (T2DM) significantly increase cardiovascular morbidity and mortality worldwide. Metabolic and bariatric surgery (MBS) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective interventions for T2DM and obesity, but comparative evidence on their long-term impact on major adverse cardiovascular events (MACE) and all-cause mortality is lacking. This systematic review and meta-analysis evaluated the efficacy of MBS versus GLP-1 RAs therapy in reducing these outcomes.

Methods

The review was registered in PROSPERO beforehand and carried out following the PRISMA framework. A comprehensive literature search identified randomized controlled trials (RCTs) and observational studies comparing MBS with GLP-1 RAs regimens in adults with obesity and T2DM. The primary outcomes were all-cause mortality and MACE. We used the Cochrane Risk of Bias 2.0 (ROB 2) tool and Newcastle-Ottawa Scale (NOS) to assess the quality of the study. Meta-analytic techniques were used to synthesize effect estimates.

Results

Pooled analysis of eligible studies suggested that MBS offered greater reductions in both MACE and all-cause mortality than GLP-1 RAs therapy. The relative risk reduction for MACE was approximately 52% in favor of MBS. Despite notable heterogeneity, sensitivity analyses confirmed result robustness. The overall certainty of evidence was moderate, reflecting variations in populations, interventions, and study designs.

Conclusion

MBS offers significantly greater cardiovascular protection than GLP-1 RAs therapy in individual with obesity and T2DM, reducing MACE and all-cause mortality. GLP-1 RAs remains an important option, particularly for patients contraindicated for surgery or preferring pharmacotherapy. Further long-term comparative and cost effectiveness studies are needed to inform the clinical decisions.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11695-026-08508-5.

Introduction

Obesity and type 2 diabetes mellitus (T2DM) are closely interrelated metabolic disorders that have reached epidemic proportions globally, contributing significantly to morbidity and mortality [1, 2]. Each five kg/m² increase in body mass index (BMI) above the normal range is associated with approximately 30% rise in overall mortality and a reduction in life expectancy of 10 years [3]. Cardiovascular diseases (CVDs) are the leading cause of death in this population, with major adverse cardiac events (MACE) including myocardial infarction (MI), stroke, and ischemic heart disease (IHD) occurring more frequently among individuals with T2DM due to chronic hyperglycemia, insulin resistance, and associated metabolic risk factors such as dyslipidaemia and hypertension [4]. As a result, effective therapeutic strategies that improve glycemic control and reduce cardiovascular risk are essential to mitigating the long-term health consequences of T2DM [5, 6].

The metabolic and bariatric surgery (MBS) has emerged as a highly effective intervention for patients with obesity and T2DM, resulting in sustained weight loss, improved glycemic control, and, in many cases, remission of diabetes approximately 31% to 56% [7–9]. After MBS, approximately 25–35% of the total body weight loss reported in the first 2–3 years, depends on surgery type, baseline BMI, DM status, and follow-up duration [10–12]. Also, the MBS confers significant cardiovascular benefits, including reductions in the incidence of MACE (HR: 0.58, 95% CI: 0.51–0.66) and all-cause mortality (HR: 0.30, 95% CI: 0.15–0.62), particularly among those with obesity and T2DM [13, 14]. However, several adverse events and postoperative complications were reported after MBS including weight regain, surgical revision, anastomotic leaks, infections, gastrointestinal (GI) bleeding and micronutrient deficiencies (zinc, vitamin A, B12 and D, iron, calcium and folate) [15–18].

In parallel, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been extensively evaluated in large randomized controlled trials (RCTs), demonstrating not only improvements in metabolic parameters but also in the reductions of cardiovascular mortality and hospitalization rates [19, 20]. The use of GLP-1 RAs including tirzepatide shows 15–25% weight reduction after one year of therapy, however weight regain also reported after discontinuation of medication [21]. And also, use of GLP-1 RAs associated with several GI adverse events, including nausea, vomiting, diarrhoea, constipation, gallbladder disorders such as cholelithiasis, and gastroesophageal reflux disease (GERD) [22–24]. Although both MBS and GLP-1 RAs are effective strategies for improving metabolic outcomes and reducing cardiovascular risk in the individual with obesity and T2DM, their risk-benefit profiles differ, and direct comparative evidence on long-term MACE and all-cause mortality is limited [25, 26].

This systematic review and meta-analysis is designed to synthesize current evidence examining the effects of MBS in comparison to GLP-1 RAs therapy on all-cause mortality and nonfatal MACE in individuals with obesity and T2DM.

Methods

This systematic review and meta-analysis was prospectively registered in PROSPERO (Prospective Register of Systematic Reviews) prior to conducting the research. We conducted the review following the standards outlined in the PRISMA framework (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [27]. The research question was formulated using the PICO (Population, Intervention, Comparator and Outcome) framework summarized in Table 1.

Table 1.

PICO components of the research question

Population	Individuals (adults) with obesity and type 2 diabetes mellitus
Intervention	Metabolic and bariatric surgery
Comparison	Glucagon-like peptide-1 receptor agonists
Outcome	All-cause mortality as a critical outcome and nonfatal major adverse cardiovascular events , including myocardial infarction, stroke, ischemic heart disease, or the need for percutaneous transluminal coronary angioplasty or coronary artery bypass graft during follow-up, as important outcomes

Eligibility Criteria

The inclusion criteria for this review were: (i) studies involving adult individuals with obesity and T2DM; (ii) studies comparing MBS with GLP-1 RAs therapy; (iii) studies reporting outcomes on all-cause mortality and/or nonfatal MACE, including MI, stroke, IHD, or coronary revascularization procedures during follow-up; (iv) RCTs and prospective or retrospective cohort studies published in peer-reviewed journals; and (v) studies published in the English language. The exclusion criteria included animal studies, case reports, case series, cross-sectional and case-control studies, conference abstracts, editorials, commentaries, and review articles without original data, as well as studies not published in English or lacking peer review.

Data Source and Eligibility Criteria

A comprehensive literature search was performed on October 31, 2024, across Medline (via PubMed), EMBASE, and Scopus databases. The search strategy was developed using Medical Subject Headings (MeSH) terms extracted from the most relevant publications. These terms were iteratively refined and expanded to improve the sensitivity and specificity of the search. The full electronic search strategy for each database is provided in Supplementary file 1.

Screening

A total of 2,826 unique records were identified from our initial search. Three reviewers (SL, VB, and JC) independently screened the titles and abstracts of all eligible studies using the Rayyan web platform. The same reviewers then assessed the full texts, and through consensus, finalized the set of 11 studies that met the inclusion criteria (Fig. 1).

Fig. 1.

PRISMA flow chart

Data Extraction and Cleaning

Data extraction was conducted independently by SL and CS based on predefined eligibility criteria. The extracted data were then carefully compiled into tables, including variables such as author, year of publication, study title, location, source and type of funding, conflict of interest disclosures, target groups, number of participants in each arm, gender breakdowns, diabetes duration, obesity classification, age distributions for intervention and control groups, comprehensive descriptions of the interventions and comparators, as well as reported outcomes like all-cause mortality and MACE in both groups.

Risk of Bias Assessment and Quality Assessment

The risk of bias for the included studies was independently evaluated by two reviewers (CS and SL) using standardized tools appropriate for each study design. For RCTs, the Cochrane Risk of Bias 2 (ROB 2) tool was applied, which evaluates five domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of the reported result. Each domain was rated as low risk, some concerns, or high risk of bias according to Cochrane guidance [28].

For observational cohort studies, the Newcastle-Ottawa Scale (NOS) was used to assess study quality across three domains: selection of participants (maximum 4 stars), comparability of cohorts (maximum 2 stars), and ascertainment of outcomes (maximum 3 stars). Studies were categorized as high quality (7–9 stars), moderate quality (5–6 stars), or low quality (< 5 stars) [29].

Any disagreements between the reviewers were resolved through discussion, and unresolved conflicts were adjudicated by a third reviewer (JC).

Data Analysis

A random-effects model, constructed with the Der Simonian and Laird method, was used to perform the meta-analysis and estimate pooled relative risk (RR). The findings were systematically presented using forest plots, emphasizing on effect measures and statistical significance.

To assess heterogeneity across studies, both the Chi-squared (χ²) test and the I² statistic were used. Subgroup analyses were performed based on country, comparator type, and study design to explore potential sources of heterogeneity. The robustness of the results was examined through a leave-one-out sensitivity analysis, which assessed the impact of excluding each study on the overall effect size, especially in the context of study quality.

Publication bias was visually assessed using a funnel plot to detect the presence of small-study effects. The overall certainty of the evidence for each outcome was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

Results

Characteristics of Included Studies

A comprehensive literature search across PubMed, Embase, and Scopus identified 4,752 unique records. After screening and removal of duplicates, 2,826 records were assessed for eligibility. Full-text review of 112 articles led to the inclusion of 11 studies comprising 19,644 individuals with obesity and T2DM. The included studies featured a mix of RCTs (n = 4), propensity score-matched cohorts (n = 3), and large nationwide matched cohorts (n = 4) [4, 26, 30–38]. Geographic distribution spanned the United States, China, Italy, Sweden, Israel, Australia, and Taiwan, reflecting a diversity of clinical settings and patient populations (Table 2). Baseline participant characteristics varied, with diabetes duration ranging from new-onset to over 10 years, and BMI generally within 25–45 kg/m². MBS predominantly involved Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), while comparator groups received GLP-1 RAs therapy primarily liraglutide, semaglutide, and dulaglutide often alongside comprehensive medical management (Table 2).

Table 2.

Characteristics of included studies

Study No.	Author/Year/Country	Design	Sample Size	Intervention	Comparator	Follow-up	Key Outcomes
1	Courcoulas et al., 2024 (USA)	Pooled Analysis of 4 RCTs	166 patients	RYGB/SG/AGB	GLP-1 RAs + medical therapy	12 years	Similar mortality and MACEs; better diabetes remission, weight loss, HbA1c in surgery
2	Qi et al., 2023 (Australia)	RCT	41	Gastric Band + MDC	MDC alone (3/20 GLP-1)	10 years	Greater weight loss and remission in surgery; no mortality or MACE difference
3	Ling et al., 2022 (China)	Propensity score-matched cohort	213 (71 RYGB)	RYGB	Medical therapy (GLP-1 use ~ 1.3%)	2 years	Better glycemic control, BP, T2DM remission, fewer CV events with RYGB
4	Zhigang et al., 2021 (China)	PSM cohort	684 (52 pairs)	RYGB/SG	Oral agents + GLP-1 (minimal use)	5 years	Reduced estimated ASCVD risk, HbA1c, BMI in surgery
5	Mingrone et al., 2021 (Italy)	RCT	72	RYGB/BPD	Medical (with GLP-1, SGLT2i)	10 years	Surgery better for glycemic control, remission; lower complications
6	Mingrone et al., 2015 (Italy)	RCT	60	RYGB/BPD	Medical (GLP-1 + drugs)	5 years	Higher remission, weight loss, lower insulin use, CHD risk in surgery
7	Ikramuddin et al., 2015 (USA/Taiwan)	RCT	120	RYGB + lifestyle	GLP-1–inclusive medical therapy	2 years	Better HbA1c, remission in RYGB; no MACE data; higher nutritional adverse events
8	Stenberg & Näslund, 2023 (Sweden)	Nationwide matched cohort	4322 (2161/group)	MBS (80.9% RYGB)	GLP-1 RAs (mostly liraglutide)	8 years	Lower mortality & MACE in MBS; better remission rates
9	Stenberg et al., 2024 (Sweden)	Matched cohort	4078	MBS (82% RYGB)	GLP-1 RAs (semaglutide 13%)	10 years	Lower MACEs, microvascular events; no mortality difference; higher self-harm/fractures in MBS
10	Dicker et al., 2024 (Israel)	Matched cohort	6070	BMS (RYGB/SG/banding)	GLP-1 RAs	1 years	Mortality benefit in short-duration diabetes (< 10 yrs); no MACE difference
11	Yael Wolff Sagy et al., 2024 (Israel)	Matched cohort	4410 (2205 pairs)	BMS	GLP-1 RAs (semaglutide 5%)	12 years	Lower CHF incidence in surgery; mortality not reported

Pooled Effect Estimates

Meta-analysis of 10 studies evaluating the MACE, revealed a significant risk reduction was associated with MBS compared to GLP-1 RAs therapy. The pooled RR was 0.48 (95% CI: 0.33–0.72; p < 0.001), indicating a 52% relative risk reduction in MACE among patients undergoing MBS when compared to GLP-1 RAs. Subgroup analysis by study design showed consistent benefit in RCTs (RR 0.31; 95% CI: 0.14–0.72) as well as observational cohorts (RR 0.57; 95% CI: 0.38–0.84) (Fig. 2).

Fig. 2.

Depicting the pooled effect of the intervention on MACE

Heterogeneity and Subgroup Analysis

Substantial heterogeneity was observed across studies (I² = 78.3%, τ² = 0.20, p < 0.001), suggesting that the variability in the study populations, intervention type and follow-up durations. However, the sensitivity analysis, using a leave-one-out approach, confirmed the robustness of the pooled estimate, with the RR remaining within the range of 0.41 to 0.56 when each study was sequentially excluded.

Subgroup analyses also revealed substantial regional variation, with the most pronounced risk reduction observed in studies from the USA (RR 0.27, 95% CI: 0.16–0.44, p < 0.001), Italy (RR 0.08, 95% CI: 0.01–0.93, p = 0.003), and Israel (RR 0.41, 95% CI: 0.21–0.79, p = 0.008), likely due to stricter surgical eligibility criteria and patient selection. In contrast, analyses by comparator type and study design did not identify significant effect modification (Fig. 3).

Fig. 3.

Depicting the heterogeneity and subgroup analysis

Publication Bias

Visual inspection of funnel plots suggested slight asymmetry consistent with mild publication bias (Fig. 4).

Fig. 4.

Depicting the small-study effects

Sensitivity Analysis (Leave-One-Out)

Leave-one-out sensitivity analyses demonstrated that no single study disproportionately altered the overall finding; the beneficial effect of bariatric surgery on MACE remained robust (RR range 0.41–0.56) (Fig. 5).

Fig. 5.

Depicting the sensitivity analysis (Leave-One-Out)

Risk of Bias and Study Quality Assessment

Among the RCTs, only three studies had some concern due to its randomization process and deviation from the intendent intervention, while all the cohort studies were rated as low ROB across all the domains (participants selection, comparability of the group and outcome assessment) (Fig. 6 and Supplementary File 2, respectively). The overall evidence was graded as moderate certainty by GRADE criteria, considering risk of bias, consistency, directness, precision, and potential reporting biases (Supplementary file 3).

Fig. 6.

Depicting risk of bias assessment using the ROB 2 tool

Discussion

This systematic review and meta-analysis compared the efficacy of MBS and GLP-1 RAs therapy in reducing all-cause mortality and MACE among individuals with obesity and T2DM. The pooled analysis demonstrated that MBS was associated with a significant reduction in the risk of MACE and all-cause mortality compared to GLP-1 RAs therapy, with a relative RR of 52%. The observed benefits of MBS extend beyond glycemic control and weight loss, likely reflecting the multifactorial impact of surgical interventions on metabolic and cardiovascular risk factors. While GLP-1 RAs have demonstrated efficacy in reducing cardiovascular events and improving metabolic parameters, the magnitude of benefit appears greater with surgical intervention, particularly over the long term [1].

Recent meta-analyses and large-scale cohort studies provide robust evidence favoring MBS over GLP-1 RAs in reducing both MACE and all-cause mortality among individuals with obesity and T2DM [1, 38, 39]. For instance, Dicker et al. (2024) and Saeed et al. (2024) demonstrated that MBS is associated with a 29–52% lower risk of MACE and a 25% reduction in mortality compared to GLP-1 RAs therapy, with these benefits being most pronounced in patients with longstanding diabetes and higher baseline cardiovascular risk [1, 38]. Additionally, MBS yields more profound and sustained weight loss, typically averaging 25–35% of baseline body weight at three years, compared to approximately 10–15% with GLP-1 RAs monotherapy [1, 39]. Although newer dual agonists such as tirzepatide can achieve greater weight loss (~ 20%), real-world data imply the durability of metabolic benefits remains superior for surgical interventions, especially given the tendency for substantial weight regain following GLP-1 RAs discontinuation [39]. However, the overall rate of serious adverse events is considered low for both interventions when patients are carefully selected and monitored [1]. Quality of life post intervention is generally reported to be higher after surgery, due to greater weight loss and improved metabolic control, but it must be weighed against surgical risks and need for lifelong nutritional monitoring [39, 40].

And also, studies documented the difference in outcome depending on the type surgical procedure (MBS). The RYGB usually done by creating a small stomach pouch and rerouting a part of small intestine, combining small restrictive and malabsorptive mechanism, whereas the SG involves removal of larger portion of stomach to restrict food intake [41]. The RYGB, generally shows greater improvement in weight reduction, insulin sensitivity and lipid metabolism compared to SG or one-anastomosis gastric bypass (OAGB) [41, 42]. The mean total body weight loss ranges from 25 to 35% after 2–3 years, with RYGB shows significant effect on diabetes remission and MACE [11].

Similarly, the safety profile and potency of GLP-1 RAs therapies also varies, liraglutide (1.8–3.0.8.0 mg) and semaglutide (2.4 mg) showed 8–15% reduction in weight loss and cardiovascular events in LEADER and SUSTAIN-6 trials, respectively [43–45]. A recent study reported that use of dual glucose dependent insulinotropic polypeptide (GIP) called trizepatide achieved approximately 20% or more in body weight loss and improvement in glycemic and lipid parameters in the SURPASS and SURMOUNT trials but frequently associated with GI adverse events which can limit the adherence [46–48].

Future research should prioritize well-powered, long-term head-to-head comparative studies directly evaluating MBS against GLP-1 RAs therapies across diverse patient populations, stratified by baseline cardiovascular risk, diabetes duration, and comorbidity profiles. Robust real-world safety surveillance including registry-based studies and pharmacovigilance efforts is needed to clarify uncommon adverse events and long-term outcomes, especially in patients receiving novel dual agonists or sequential therapy post-bariatric surgery. Comparative cost-effectiveness analyses, incorporating longitudinal direct and indirect medical costs, quality of life measures, and patient-reported outcomes, will be essential to inform policy and clinical decision-making as the therapeutic landscape evolves. Multicenter RCTs and pragmatic effectiveness studies must also address the impact of integrated or combination therapy approaches, such as GLP-1 RAs use following MBS, optimizing patient-centred strategies for weight loss, metabolic control, and cardiovascular risk reduction. Finally, ongoing research into mechanisms of cardiometabolic benefit and heterogeneity of response will further refine personalized treatment pathways.

Strengths and Limitations

A key strength of this systematic review is its comprehensive scope, leveraging recent multicenter studies and meta-analyses (2024–2025) that provide cutting-edge comparisons of MBS and GLP-1 RAs for MACE and mortality in diverse populations. Notably, the analysis incorporates real-world cohorts as well as RTCs, enabling broader generalizability of results. However, several limitations warrant consideration. The included studies are predominantly observational, introducing potential confounding and bias, despite adjustment for known risk factors. Heterogeneity in patient populations (e.g., baseline BMI, duration of diabetes), intervention details (surgery types and GLP-1 RAs agents), and outcome definitions may limit direct comparability across studies. Follow-up durations vary, and some important endpoints (e.g., long-term adverse events, cost-effectiveness) are less frequently reported in the medication arms. Finally, limited head-to-RTCs remain an important evidence gap, emphasizing the need for future research to clarify risk–benefit profiles and optimize patient-centered therapy selection. Finally, while sensitivity analyses confirmed the stability of the main findings, the potential for publication bias cannot be entirely excluded.

Conclusion

In summary, recent evidence from large-scale meta-analyses and cohort studies indicates that MBS produces greater reductions in MACE, all-cause mortality, and sustained weight loss compared to GLP-1 RAs therapy among individuals with obesity and T2DM. While both approaches offer substantial clinical benefit, MBS provides more pronounced and durable risk reduction, particularly in those with longstanding diabetes and elevated cardiovascular risk, albeit at the expense of greater perioperative and nutritional risks. GLP-1 RAs remain an essential therapeutic option for patient’s ineligible for surgery or seeking non-surgical management, though weight regain and long-term cardiovascular outcomes warrant careful consideration. Clinicians should individualize therapy based on patient risk profiles, preferences, and access, with future research needed to clarify the optimal sequencing and combination of interventions, long-term safety, and cost-effectiveness in real-world practice.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

JC, BSB, CS and GKP conceptualized the study. Data curation was carried out by SL and CS, while formal analysis was performed by SL and BSB. The initial draft of the manuscript was prepared by JC, CS, and SL. All authors contributed to the critical review and editing of the manuscript, approved the final version for publication. JC served as the guarantor of this work.

Funding

There is no funding source for conducting this systematic review.

Data Availability

The datasets generated and/or analyzed during the present study are not publicly available. However, they can be made available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.