Reviewed by Dr Reza Lankarani, General Surgeon

Founder | Surgical Pioneering Newsletter and Podcast Series

Editorial Board Member | Genesis Journal of Surgery and Medicine

Summary

This document synthesizes findings from a five-year retrospective study on the long-term outcomes of Laparoscopic Sleeve Gastrectomy (LSG) in adolescents. The research confirms that LSG is a highly effective intervention, yielding substantial and sustained weight loss and significant resolution of metabolic comorbidities. However, the study highlights that a notable subset of patients (23.5%) experiences clinically significant weight regain (WR), a phenomenon linked to both anatomical and hormonal factors.

The core mechanism investigated is the post-surgical trajectory of the incretin hormones GLP-1 and GIP. While all patients experience an initial beneficial surge in these hormones, this effect attenuates over time. In patients with WR, this hormonal decline is more pronounced and occurs earlier. The study demonstrates that a one-year course of the GLP-1 receptor agonist semaglutide can partially reverse WR, increasing mean excess weight loss from 34% to 68% in affected patients. Key indicators associated with WR include larger remnant gastric volumes and attenuated postprandial hormone responses. These findings underscore the potential for a more tailored post-LSG management approach, incorporating hormonal surveillance and timely pharmacological intervention to optimize long-term success.

--------------------------------------------------------------------------------

1. Study Overview and Methodology

The research provides a comprehensive five-year analysis of adolescent outcomes following Laparoscopic Sleeve Gastrectomy (LSG), focusing on weight loss, hormonal changes, and the impact of pharmacological intervention for weight regain.

* Objective: To evaluate the long-term weight and incretin hormone (GLP-1 and GIP) trajectories after LSG in adolescents and to assess the impact of adjunctive semaglutide therapy for patients experiencing weight regain.

* Cohort Profile: The study included 264 adolescents who completed a five-year follow-up.

* Mean Age: 15.04 ± 2.99 years

* Sex Distribution: 73.86% female, 26.14% male

* Mean Preoperative Weight: 132.8 ± 9.67 kg

* Mean Preoperative BMI: 48.38 ± 6.95 kg/m²

* Procedure and Follow-up: All patients underwent a standardized LSG procedure with antral resection. Postoperative evaluations, including anthropometric and hormonal measurements, were conducted annually for five years. The study maintained a high retention rate of 90.1%.

* Weight Regain (WR) Definition: Clinically significant WR was defined as a weight gain of ≥10% from the nadir (lowest) postoperative weight, combined with less than 50% excess weight loss (%EWL) at 18 months post-surgery.

* Pharmacological Intervention: 62 patients (23.48%) met the WR criteria. At the start of the third postoperative year (and upon reaching at least 18 years of age), they received a 12-month course of semaglutide, followed by a three-month tapering period.

2. Core Findings: Weight Loss and Metabolic Outcomes

LSG produced significant and sustained improvements in weight and metabolic health over the five-year period, although a pattern of peak weight loss followed by partial regain was observed.

Weight Trajectory and Gastric Volume

Weight loss peaked at two years post-surgery, followed by a gradual and slight regain. Concurrently, the volume of the remnant stomach progressively increased over the five years.

Comorbidity Resolution

The procedure led to profound and statistically significant improvements in major obesity-related comorbidities, with benefits sustained and enhanced throughout the five-year follow-up.

Comorbidity Preoperative Prevalence 5-Year Prevalence

Type 2 Diabetes 36.36% 5.68%

Hypertension 48.86% 6.82%

Dyslipidemia 43.18% 4.55%

Furthermore, mean HbA1c levels improved significantly, falling from a baseline of 7.12% to 5.36% at year five.

3. The Role of Incretin Hormones (GLP-1 & GIP)

The study provides novel insights into the hormonal adaptations following LSG and their association with weight management.

* Overall Hormonal Response: The entire cohort exhibited a marked post-operative surge in both GLP-1 and GIP levels. This enhancement was highest during the first postoperative year, particularly at 30 and 60 minutes after a meal. Following this peak, the hormonal response gradually diminished over time, with levels approaching preoperative values by the fifth year.

* Hormonal Patterns in Weight Regain: The subgroup of patients who experienced clinically significant WR demonstrated a similar initial hormonal surge. However, the subsequent decline in their GLP-1 and GIP levels was more pronounced and occurred earlier compared to patients who maintained their weight loss.

* Comparative Analysis: A direct comparison between the WR and non-WR groups revealed that at year three, WR patients had significantly lower postprandial GLP-1 and GIP levels. This suggests that an early attenuation of the incretin response is temporally associated with a higher risk of weight regain.

4. Semaglutide as an Adjunctive Therapy for Weight Regain

The study evaluated semaglutide as a "rescue" therapy for the 62 patients who met the criteria for significant WR.

* Efficacy: The intervention proved effective at reversing the trend of weight regain. Before treatment, the WR group's mean %EWL had fallen from 63.3% at year one to 34.1% at year two. Following the one-year course of semaglutide initiated at year three, their mean %EWL rose to 68%.

* Durability of Effect: The positive effects of semaglutide were partially transient. After the 12-month treatment course and subsequent taper, the mean %EWL in this group gradually decreased to 64.1% at year four and 58.3% at year five. This indicates that the benefits are closely tied to active treatment and may diminish upon cessation.

* Underlying Mechanism: The findings support the hypothesis that post-surgical WR is partly driven by diminishing endogenous incretin responses. Pharmacological intervention with a GLP-1 receptor agonist like semaglutide effectively compensates for this decline, restoring weight loss momentum.

5. Key Indicators and Clinical Implications

The research identifies key factors associated with long-term outcomes and suggests pathways for improving postoperative care.

Factors Associated with Weight Regain

Two primary factors were consistently correlated with clinically significant WR in the cohort:

1. Anatomical Factors: A larger remnant gastric volume at five years was strongly associated with the WR group (222.1 mL vs. 192.3 mL in the non-WR group). Larger volumes may permit greater food intake and reduce satiety.

2. Hormonal Factors: An earlier and more significant attenuation of postprandial GLP-1 and GIP responses was observed in patients with WR, suggesting this pattern may serve as a potential biomarker for increased risk.

Clinical Implications

The study's findings support a shift toward more proactive and individualized long-term management following adolescent LSG.

* Potential for Hormonal Surveillance: Monitoring postprandial gut hormone responses may help identify patients at higher risk for WR, allowing for earlier intervention.

* Role of Adjunctive Pharmacotherapy: GLP-1 receptor agonists like semaglutide represent a valuable tool for managing WR, offering a "rescue" strategy for patients with suboptimal outcomes.

* Tailored Postoperative Care: The results advocate for a management strategy that integrates anatomical assessment (e.g., gastric volume), hormonal monitoring, and timely pharmacological support to enhance the durability of surgical success.

6. Study Limitations and Conclusion

While providing valuable long-term data, the study acknowledges several limitations, including its retrospective, single-center design, the absence of a randomized control group for the semaglutide intervention, and the fact that hormonal measurements were conducted on patients actively taking the medication. The analysis was descriptive and did not perform formal correlation testing between hormone levels and weight outcomes.

In conclusion, LSG is a highly effective intervention for adolescent obesity, delivering substantial five-year improvements in weight and metabolic health. The study successfully illuminates the dynamic role of incretin hormones, where an initial surge is followed by a gradual decline that is more pronounced in individuals who experience weight regain. Adjunct semaglutide therapy can effectively, though temporarily, reverse this regain. The association between attenuated hormone levels, increased gastric volume, and WR highlights the need for prospective research to validate these factors as predictive biomarkers and to guide the development of optimized, individualized long-term care strategies.

To access additional details, please refer to the Surgical Pioneering Podcast Series application available at the following link:

https://Surgicalpioneer.codeadx.me

Get full access to Reza Lankarani at lankarani.substack.com/subscribe