Published on: 21 July 2025

Introduction

Obesity remains a significant public health issue in the United States, with over 40% of adults classified as obese and projections indicating this could rise to over 50% by 2030. Bariatric surgery is currently the gold standard for sustainable weight loss and metabolic control in patients with severe obesity. Among bariatric procedures, sleeve gastrectomy has become the most commonly performed surgery in the US since its endorsement as a standalone procedure by the American Society for Metabolic and Bariatric Surgery in 2012.

While sleeve gastrectomy offers lower complication rates and comparable short- and long-term outcomes relative to Roux-en-Y gastric bypass (RYGB), a significant proportion of patients experience insufficient weight loss or weight regain following the procedure. Published rates of such suboptimal outcomes vary from 13% to nearly 28%, depending on the criteria used.

Traditionally, treatment options for patients with inadequate weight loss or weight recurrence after sleeve gastrectomy included lifestyle interventions or revisional bariatric surgeries such as conversion to RYGB or other malabsorptive procedures. More recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs), including semaglutide and tirzepatide, have emerged as effective pharmacologic therapies for obesity, demonstrating marked weight loss and improved glycemic control in non-surgical populations. This raises the question of whether GLP1-RAs could serve as a less invasive alternative to surgical conversion for patients with failed sleeve gastrectomy outcomes.

The purpose of this study was to compare the efficacy of conversion to RYGB (cRYGB) versus treatment with injectable GLP1-RAs in patients who had insufficient weight loss or weight recurrence after sleeve gastrectomy. The primary outcome was percentage total body weight loss (%TBWL) up to three years post intervention. Secondary outcomes included changes in hemoglobin A1c (HgbA1c) and medication prescription patterns.

Methods

This retrospective multicenter study analyzed data from two large academic health systems, integrating electronic health records (EHR) and the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) databases. The study was IRB approved, with informed consent waived.

Inclusion criteria were adult patients (≥18 years) who had previously undergone sleeve gastrectomy and subsequently either:

• Received weekly injectable semaglutide or tirzepatide, or
• Underwent conversion from sleeve gastrectomy to RYGB between January 1, 2018, and July 31, 2024.

Patients were excluded if they:

• Had GLP1-RA treatment with BMI ≤ 35 (to exclude those treated solely for diabetes),
• Were converted to RYGB for gastroesophageal reflux disease (GERD),
• Had pre-operative GLP1-RA use, or
• Had any bariatric procedure prior to their index sleeve gastrectomy.

Demographic and clinical variables collected included age, sex, baseline weight and BMI, baseline HgbA1c, race/ethnicity, insurance type, and comorbidities such as diabetes, hypertension, hyperlipidemia, sleep apnea, liver disease, smoking status, steroid use, COPD, and renal disease.

The primary outcome, %TBWL, was measured at 3 months, 6 months, 1 year, 2 years, and 3 years post intervention (start of GLP1-RA or surgery). Secondary outcomes included changes in HgbA1c and patterns of GLP1-RA prescription over time.

Statistical analyses used included t-tests, chi-squared tests, Kaplan–Meier survival analysis for medication persistence, and multivariate linear regression adjusting for sex, age, baseline BMI, HgbA1c, and race.

Results

A total of 4,901 patients were analyzed: 3,004 underwent cRYGB and 1,897 were treated with GLP1-RAs.

• Baseline characteristics showed cRYGB patients were younger (mean 38.2 vs. 46.7 years), had a slightly higher BMI (41.1 vs. 39.7), and higher baseline HgbA1c (6.19% vs. 5.85%) compared to GLP1-RA patients.
• GLP1-RA patients had a higher prevalence of diabetes (28.3% vs. 19.7%) and were more often on insulin (17.9% vs. 5.6%), while hypertension was more common in cRYGB patients (94.1% vs. 35.7%).
• The racial/ethnic composition differed, with GLP1-RA patients more likely to be White (40.6% vs. 10.2%) and cRYGB patients more likely Hispanic (33.4% vs. 24.4%).
• Insurance status also differed, with more cRYGB patients on non-commercial insurance (28% vs. 21%).

Among those with data on their index sleeve gastrectomy (n=3,336), GLP1-RA patients had higher pre-sleeve weights and maximum post-sleeve weights but similar nadir weights post sleeve.

GLP1-RA treatment duration averaged 11.3 months, with most patients discontinuing by 2 years (90% off medication) and 98% by 3 years. Tirzepatide patients tended to remain on treatment longer than semaglutide patients (13.5 vs. 9.4 months), though this difference wasn’t statistically significant.

Weight Loss Outcomes

• Conversion to RYGB was associated with significantly greater %TBWL at all post-intervention time points, from 3 months up to 3 years.
• The greatest difference was observed at 1 year post intervention (30.4% TBWL for cRYGB vs. 13.1% for GLP1-RA). At 3 years, the difference remained significant (26.1% vs. 13.7%).
• When analyzed by GLP1-RA subtype, both semaglutide and tirzepatide yielded less weight loss compared to cRYGB, with no significant difference between the two medications themselves.

HgbA1c Outcomes

• There was no significant difference in HgbA1c control between the cRYGB and GLP1-RA groups at any post-intervention time point.
• Similarly, no differences were observed between semaglutide and tirzepatide subgroups regarding glycemic control.

Multivariate Analysis

After adjusting for sex, baseline BMI, age, and race, cRYGB was associated with an 11% greater %TBWL at 3 years post intervention compared to GLP1-RA treatment. There was no evidence of multicollinearity among variables.

Discussion

This large multicenter retrospective study provides important comparative data on treatment options for patients with suboptimal weight loss or weight recurrence after sleeve gastrectomy.

• Efficacy of cRYGB: The findings support conversion to RYGB as a superior option for sustained weight loss, with an average 26.1% TBWL at 3 years, which is higher than previously reported short-term studies.
• GLP1-RA effectiveness: GLP1-RAs, although less effective than conversion surgery, still provided meaningful weight loss (average 13% TBWL), consistent with prior smaller studies and clinical trials.
• Medication persistence: High discontinuation rates for GLP1-RAs were observed, consistent with other real-world studies showing 36–50% discontinuation by one year. Interestingly, tirzepatide patients tended to have longer treatment durations than semaglutide patients, despite higher costs, suggesting factors beyond cost influence adherence.
• Sustained weight loss post-discontinuation: Unlike prior reports where weight regain occurred after stopping GLP1-RAs, this cohort showed sustained weight loss after cessation, possibly due to the combined effect of prior bariatric surgery and pharmacotherapy or patient management factors.
• Glycemic control: No significant differences in HgbA1c outcomes between surgical and pharmacologic treatments were noted, though baseline glycemic status was largely non-diabetic, limiting conclusions on diabetes control.

Limitations

• Reliance on medication orders rather than pharmacy fill data could overestimate treatment adherence.
• Only RYGB was studied as a conversion surgery; other revisional procedures with potentially higher weight loss but also higher morbidity were excluded.
• Some index sleeve gastrectomies were performed outside the included systems, potentially introducing variability in initial surgical management.
• The observational design limits causal inference.

Conclusions

For patients experiencing insufficient weight loss or weight recurrence following sleeve gastrectomy, conversion to RYGB offers significantly greater long-term weight loss compared to treatment with GLP1-RAs such as semaglutide or tirzepatide. While GLP1-RAs provide a non-invasive alternative with moderate effectiveness, sustained weight loss was more robust with surgical revision up to three years post intervention.

These findings inform clinical decision-making and highlight the need for individualized treatment plans. Future research should focus on identifying patient characteristics that predict success with pharmacotherapy versus surgery and further explore the optimal integration of these treatments.

SOURCE/READ THE FULL ARTICLE: https://pubmed.ncbi.nlm.nih.gov/40691334/

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