Clinical trial NCT06820047: Sleeve Gastrectomy vs. Lifestyle & Medications: Impact on BMI Trajectory and Target Attainment in a Matched Cohort Study
Official title: Impact of Sleeve Gastrectomy Versus Intensive Lifestyle Modifications With Obesity Management Medications on BMI Trajectory and Target Attainment: a Prospective Matched Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity and Obesity-related Medical Conditions
Keywords: obesity
sleeve gastrectomy
semaglutide
glp-1 receptor agonist
intensive lifestyle modifications
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2025-02-11
Enrollment: 190
Sex: ALL
Minimum age (years): 19
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients attending the weight-loss clinic of Sapienza University Hospital and Catholic University Hospital in Rome, Italy, and eligible for bariatric surgery were allocated to intensive lifestyle modifications with obesity management medications or metabolic surgery.

Brief summary: Obesity is a widespread and preventable condition affecting over a billion people globally, with rates expected to rise significantly by 2030. It increases the risk of chronic illnesses such as diabetes, cardiovascular disease, certain cancers, mental health issues, and premature death. While bariatric surgery, such as sleeve gastrectomy (SG), is the most effective long-term weight-loss solution, many individuals are ineligible or unwilling to undergo surgery. Semaglutide, a medication that suppresses appetite and aids in weight loss when paired with diet and exercise, offers a promising alternative. This study compared the effectiveness of SG and an intensive weight-loss program combining diet, exercise, and semaglutide. Conducted over a year with 190 participants split into two groups matched by BMI, the SG group underwent surgery, while the other group followed a calorie-restricted diet, intensive exercise, and weekly semaglutide injections. Changes in BMI, weight, and comorbidities such as diabetes and high blood pressure were evaluated, aiming to determine which approach was more effective in managing obesity.

Detailed description: Obesity is a complex and largely preventable disease affecting over a third of the global population. As of 2022, more than 1 billion individuals worldwide were living with obesity, and projections indicate that by 2030, 38% of the adult population will be overweight, with an additional 20% affected by obesity. This condition significantly increases the risk of chronic diseases, including type 2 diabetes (T2D), cardiovascular disease (CVD), certain cancers, and mental health disorders such as depression, as well as premature mortality.

Given the rising prevalence of obesity, effective intervention strategies are critical. Bariatric and metabolic surgery remains the most effective approach for sustained weight loss, with procedures recommended for individuals with a body mass index (BMI) ≥35 kg/m², regardless of comorbidities. Metabolic surgery has demonstrated superior outcomes in reducing blood glucose levels and achieving higher remission rates of T2D compared to lifestyle and pharmacological interventions. However, surgical interventions are typically reserved for individuals who have failed prior dietary and exercise-based interventions, have adequate motivation, and do not suffer from severe psychiatric conditions.

For individuals who are ineligible for or unwilling to undergo bariatric surgery, alternative treatment options are necessary. One such option is semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, which mimics endogenous GLP-1 to suppress appetite, reduce glucagon release, and promote satiety. Studies have shown that GLP-1 receptor agonists contribute to significant weight loss and metabolic improvements.

This study aims to compare the efficacy of intensive lifestyle modifications combined with obesity management medications (ILM/OMMs) versus sleeve gastrectomy (SG) in terms of BMI trajectory and metabolic outcomes over a 1-year period. The primary endpoint is the change in BMI at 1 year, while secondary endpoints include changes in weight, plasma glucose levels, lipid profiles, and obesity-related comorbidities such as hypertension, CVD, dyslipidemia, and T2D.

Methods Study Design This study is a 1-year, prospective, multicenter, matched cohort study comparing ILM/OMMs with SG. Patients were recruited from the weight-loss clinics of Sapienza University Hospital and Catholic University Hospital in Rome, Italy. Eligible patients were allocated to either ILM/OMMs or SG. Ninety-five patients per arm were matched in a 1:1 ratio, based on sex, age, BMI, and diabetes duration.

The study was conducted between May 2022 and July 2024, following the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) reporting guidelines for cohort studies. Ethical approval was obtained from both institutions, and the study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants, with additional consent required for patients undergoing bariatric surgery.

Participants

Inclusion criteria:

Age 19-69 years Stable body weight for the past 6 months BMI ≥35 kg/m² with at least one obesity-related comorbidity (T2D, hypertension, sleep apnea, metabolic-associated fatty liver disease, osteoarthritis, dyslipidemia, gastrointestinal disorders, or heart disease) or BMI ≥40 kg/m²

Exclusion criteria:

Previous bariatric surgery History of pancreatitis Severe psychiatric disorders Personal or familial history of endocrine cancers

Interventions Medical Arm (ILM/OMMs Group) Participants underwent a 1-month very low-calorie diet (VLCD) of 813 kcal/day, followed by an 11-month low-calorie diet (LCD), combined with structured physical activity (30 minutes/day of brisk walking and at least 3 hours/week of aerobic exercise). Additionally, they received 2.4 mg/week of semaglutide (Ozempic®) administered as a subcutaneous injection. Clinical evaluations were conducted at baseline and at 1, 3, 6, 9, and 12 months.

Surgical Arm (SG Group) Patients underwent SG, a procedure involving the longitudinal resection of approximately 75% of the stomach along its greater curvature, including the excision of the fundus, part of the body, and antrum while preserving the pylorus. Following surgery, patients were allowed a free diet. Clinical evaluations were performed at baseline and at 1, 3, 6, 9, and 12 months.

Outcome Measures The primary endpoint was the change in BMI at 1 year and the time required to achieve a 25% reduction in BMI. Secondary endpoints included changes in weight, plasma glucose levels, lipid profiles, and obesity-related comorbidities such as hypertension, CVD, dyslipidemia, and T2D at 1 year from baseline.

Body weight and height were measured using calibrated scales with participants wearing light clothing. The percentage of total body weight loss was calculated using the formula:

Sample Size Calculation To determine equivalence between the surgical and ILM/OMMs groups, the study was powered to detect a true mean difference of 3% in weight loss (25% in ILM/OMMs vs. 28% in SG) with an equivalence margin of 5%. Assuming a standard deviation of 3.4%, a sample size of 76 patients per group (alpha = 0.05, power = 90%) was required. Considering a 20% attrition rate, the final sample size was set at 190 patients (95 per group).

Statistical Analysis To assess treatment equivalence in percentage weight loss, a t-test was performed. Changes in clinical outcomes were analyzed using t-tests or Mann-Whitney U tests for continuous variables and chi-squared or Fisher's exact tests for categorical variables. Logistic regression models were used to compare response curves for weight loss and comorbidity resolution, adjusting for covariates. Continuous data were expressed as mean ± standard deviation (SD), while categorical variables were presented as counts and percentages. All statistical analyses were performed using SPSS Statistics v.27.0

Eligibility criteria: Inclusion Criteria:

* Age between 19 and 69 years with stable body weight in the past 6 months;
* BMI ≥35 kg/m2 and at least one or more obesity-related co-morbidities (T2D, hypertension, sleep apnea and other respiratory disorders, metabolic-associated fatty liver disease, osteoarthritis, lipid abnormalities, gastrointestinal disorders, or heart disease)
* BMI≥40 kg/m2 with or without related comorbidities

Exclusion Criteria:

* Previous bariatric surgery;
* History of pancreatitis;
* Severe psychiatric disorders;
* Personal or familiar history of endocrine cancers.

Primary outcomes:
measure: Weight modifications
timeFrame: 12 months
Secondary outcomes:
measure: Glycemic control changes
timeFrame: 12 months
measure: Lipid profile changes
timeFrame: 12 months
measure: Comorbidity resolution rate
timeFrame: 12 months
measure: Comorbidity resolution rate
timeFrame: 12 months
measure: Comorbidity resolution rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: IRCCS Catholic University of Rome
city: Rome
country: Italy
facility: Sapienza University of Rome
Study officials:
affiliation: University of Roma La Sapienza
name: Lidia Castagneto Gissey, MD, PhD
role: STUDY_DIRECTOR
References: