Clinical trial NCT06287307: Semaglutide 2.4mg for Low Responders After Bariatric Surgery
Official title: Semaglutide 2.4mg for Low Responders After Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Obesity
Obesity, Morbid
Weight Gain
Keywords: Obesity
Semaglutide
GLP-1
Bariatric Surgery
Weight Loss
Lead sponsor: Zuyderland Medisch Centrum
Sponsor class: OTHER
Collaborators: name: Nederlandse Obestias Kliniek (NOK)
First posted: 2024-03-01
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In 20 - 30% of the patients, the low responders, sufficient weight loss is not achieved after bariatric surgery. Secondary and/or tertiary bariatric procedures can lead to successful weight loss and resolution of comorbid conditions though, morbidity and mortality rates of these procedures are high. Therefore, additional pharmacotherapy has been suggested. Semaglutide is one of the medications that might improve outcome in the post-bariatric population. Semaglutide is a Glucagon-like peptide-1 (GLP-1) receptor analogue developed to treat type 2 diabetes. It causes glucose-dependent insulin secretion, promotes satiety and inhibits glucagon secretion. In obese (non-bariatric) patients, semaglutide has shown to improve glycemic control, decrease blood pressure, lower cardiovascular risk, and decrease body weight.

Detailed description: The treatment of obesity can be divided into three different fields: non-surgical interventions (e.g. endoscopic techniques, swallowable gastric balloon), pharmacological, and surgical treatment. All these different fields have, as their cornerstone of treatment, lifestyle interventions. Lifestyle interventions have an emphasis on regulation of energy intake and improvement of physical activity. All treatment options are adjunct to the lifestyle interventions. Besides, not all overweight or obese people are eligible for all types of treatment. For instance, pharmacological treatment options are advised in patients with a Body Mass Index (BMI) ≥ 30kg/m2 or a BMI ≥ 27kg/m2 with an obesity-related comorbidity, such as hypertension or diabetes mellitus. Several pharmaceutical agents have been developed for treatment of obesity. These medications generally affect appetite and cause weight loss only when the agent is taken in adjunct to lifestyle modification. Mean weight loss with pharmacological treatment ranges between 4.4 and 14.3%, depending on type of medication and treatment regime.

Bariatric surgery, also called metabolic surgery, includes a variety of surgical procedures in which the gastro-intestinal tract is altered. The most performed types of surgery are the Sleeve Gastrectomy (SG) and the Roux-en-Y gastric bypass (RYGB). All types of surgery cause changes in gut hormones, bile acids and microbiota, which subsequently induce changes in appetite and energy expenditure and thereby causing weight loss. Surgery is generally advised to patients with a BMI ≥ 40kg/m2 or a BMI ≥ 35kg/m2 with comorbid conditions. Compared to lifestyle intervention programs, bariatric surgery has proven to be a superior treatment for morbid obesity. Total weight loss (TWL) is about 20 - 30 %. In addition, bariatric surgery positively influences comorbid conditions, like type 2 diabetes, hypertension, cancer incidence, cardiovascular events and cardiovascular deaths. Thus, currently, bariatric surgery is the most effective treatment for morbid obesity.

However, there is a significant proportion of patients who do not reach "successful" weight loss after bariatric surgery. These patients can be divided in patients who do not reach sufficient weight loss, low responders, and patients who experience weight regain. Although there is no guideline to define who are low responders and what is significant weight regain, unsuccessful weight loss seems to occur in about 20-30% of the population. One of the best predictors of low weight loss in the long-term after surgery is 3-month weight loss. Therefore, this study's clinic provides an extra intervention for the patients who are considered low responders at the 3-month follow-up moment after surgery. The NOK defines a low responder by percentage total weight loss (%TWL) at the 3-month follow-up moment compared to expected weight loss. When %TWL is below the 25% quartile of expected weight loss the patient is considered a low responder. The expected weight loss is determined based on this clinics database of previous patients with the same baseline Body Mass Index (BMI above or below 50 kg/m2), gender and type of surgery. Thus, in the current treatment program patients have a medical consultation in which weight loss is determined three months after surgery. Based on baseline weight and exact number of days after surgery it is calculated whether the patient is a low responder with respect to a private database (currently about 6000 patients). If a patient is considered a low responder then the patient will receive three extra counselling sessions focusing on improving weight loss outcome. This extra intervention is called the plus module and is an addition to the standard program, which consists of multidisciplinary group counselling before and after surgery.

Secondary and/or tertiary bariatric procedures are performed in up to 25% of the patients with unsuccessful weight loss. Although additional surgery can lead to successful weight loss and resolution of comorbid conditions, morbidity and mortality rates of these procedures are higher. Therefore, attention has been focused on pharmacological treatment as an addition to bariatric surgery.

One of the agents that has been suggested for additional pharmacological treatment is semaglutide. Semaglutide is a Glucagon-like peptide-1 (GLP-1) receptor analogue which was initially developed to treat type 2 diabetes. GLP-1 is one of the incretins, a peptide hormone which is normally secreted from L cells in the distal ileum and colon. When secreted, GLP-1 causes an increase in insulin secretion of the beta-cells of the pancreas and a decrease of glucagon production of the alfa-cells. These changes cause a decrease of fasting and post prandial plasma glucose. In addition, GLP-1 also causes delayed gastric emptying. In non-bariatric patients, semaglutide has shown to improve glycaemic control, decrease blood pressure, lower cardiovascular risk and decrease body weight up to one year.

In this trial the effect of semaglutide 2.4 mg once weekly to the plus module for low responders on the improvement of weight loss compared to patient solely receiving the plus module will be evaluated.

Eligibility criteria: Inclusion Criteria:

* BMI before surgery was ≥ 35.0 kg/m2
* Patient is treated with group consultation at the NOK
* Patient has undergone a primary (banded) RYGB or (banded) sleeve gastrectomy (SG)
* Patient is in the lowest %TWL quartile, 3 months after surgery and will be enrolled in the plus module.

Exclusion Criteria:

* Gastropareses or gastro-intestinal complaints after bariatric surgery
* Type 1 or type 2 diabetes and/or diabetic retinopathy
* Decreased renal function (creatinine clearance \< 30 ml/min)
* Liver failure (all)
* Congestive heart failure or angina pectoris NYHA class III and IV
* Malignancy in history
* Pancreatitis (in history)
* (expected) Pregnancy / breast-feeding
* Inflammatory Bowel Disease
* Thyroid malignancy in history
* Use of warfarin or other coumarin derivates

Primary outcomes:
measure: Weight change from start study at 3 months post operative until 15 months later
timeFrame: 15 months
measure: Difference between placebo group and treatment group in weight change
timeFrame: 15 months
Secondary outcomes:
measure: Weight loss 3 months after surgery
timeFrame: 3 months
measure: Weight loss 6 months after surgery
timeFrame: 6 months
measure: Weight loss 12 months after surgery
timeFrame: 12 months
measure: Weight loss 18 months after surgery
timeFrame: 18 months
measure: Metabolic health before surgery (bloodpressure)
timeFrame: Screening for surgery
measure: Metabolic health before surgery (HbA1c)
timeFrame: Screening for surgery
measure: Metabolic health before surgery (glucose)
timeFrame: Screening for surgery
measure: Metabolic health before surgery (triglyceride)
timeFrame: Screening for surgery
measure: Metabolic health before surgery (LDL)
timeFrame: Screening for surgery
measure: Metabolic health before surgery (HDL)
timeFrame: Screening for surgery
measure: Metabolic health before surgery (total cholesterol)
timeFrame: Screening for surgery
measure: Metabolic health 3 months after surgery (Bloodpressure)
timeFrame: 3 months
measure: Metabolic health 3 months after surgery (HbA1c)
timeFrame: 3 months
measure: Metabolic health 3 months after surgery (glucose)
timeFrame: 3 months
measure: Metabolic health 3 months after surgery (triglyceride)
timeFrame: 3 months
measure: Metabolic health 3 months after surgery (LDL)
timeFrame: 3 months
measure: Metabolic health 3 months after surgery (HDL)
timeFrame: 3 months
measure: Metabolic health 3 months after surgery (total cholesterol)
timeFrame: 3 months
measure: Metabolic health at 6 months after surgery (bloodpressure)
timeFrame: 6 months
measure: Metabolic health at 6 months after surgery (HbA1c)
timeFrame: 6 months
measure: Metabolic health at 6 months after surgery (glucose)
timeFrame: 6 months
measure: Metabolic health at 6 months after surgery (triglyceride)
timeFrame: 6 months
measure: Metabolic health at 6 months after surgery (LDL)
timeFrame: 6 months
measure: Metabolic health at 6 months after surgery (HDL)
timeFrame: 6 months
measure: Metabolic health at 6 months after surgery (total cholesterol)
timeFrame: 6 months
measure: Metabolic health at 12 months after surgery (bloodpressure)
timeFrame: 12 months
measure: Metabolic health at 12 months after surgery (HbA1c)
timeFrame: 12 months
measure: Metabolic health at 12 months after surgery (glucose)
timeFrame: 12 months
measure: Metabolic health at 12 months after surgery (triglyceride)
timeFrame: 12 months
measure: Metabolic health at 12 months after surgery (LDL)
timeFrame: 12 months
measure: Metabolic health at 12 months after surgery (HDL)
timeFrame: 12 months
measure: Metabolic health at 12 months after surgery (total cholesterol)
timeFrame: 12 months
measure: Metabolic health at 18 months after surgery (bloodpressure)
timeFrame: 18 months
measure: Metabolic health at 18 months after surgery (HbA1c)
timeFrame: 18 months
measure: Metabolic health at 18 months after surgery (glucose)
timeFrame: 18 months
measure: Metabolic health at 18 months after surgery (triglyceride)
timeFrame: 18 months
measure: Metabolic health at 18 months after surgery (LDL)
timeFrame: 18 months
measure: Metabolic health at 18 months after surgery (HDL)
timeFrame: 18 months
measure: Metabolic health at 18 months after surgery (total cholesterol)
timeFrame: 18 months
measure: Health-related quality of life also related to gastro intestinal symptoms before surgery
timeFrame: Screening for surgery
measure: Health-related quality of life also related to gastro intestinal symptoms 3 months after surgery
timeFrame: 3 months
measure: Health-related quality of life also related to gastro intestinal symptoms 6 months after surgery
timeFrame: 6 months
measure: Health-related quality of life also related to gastro intestinal symptoms
timeFrame: 12 months
measure: Health-related quality of life also related to gastro intestinal symptoms
timeFrame: 18 months
measure: Cardiorespiratory fitness level before surgery
timeFrame: Screening for surgery
measure: Cardiorespiratory fitness level 3 months after surgery
timeFrame: 3 months
measure: Cardiorespiratory fitness level 6 months after surgery
timeFrame: 6 months
measure: Cardiorespiratory fitness level 12 months after surgery
timeFrame: 12 months
measure: Cardiorespiratory fitness level 18 months after surgery
timeFrame: 18 months
measure: Change in liver fat and liver stiffness at start of treatment
timeFrame: Screening for study
measure: Change in liver fat and liver stiffness 15 months after semaglutide start
timeFrame: 15 months
measure: To describe the persistence of therapy
timeFrame: 15 months
measure: To describe the average weekly dose
timeFrame: 15 months
Other outcomes:
Locations:
Study officials:
affiliation: Zuyderland Medical Center
name: Jan Willem Greve, prof
role: PRINCIPAL_INVESTIGATOR
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