Intensive Lifestyle Modifications With or Without Liraglutide 3 mg Versus Sleeve Gastrectomy: A 3 Arm Randomized Controlled Pilot Study (LETHE)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- Change of baseline BMI
Study Overview
Brief Summary
Background/Objectives: Only 1% of the clinically eligible subjects receive surgical treatment for their obesity, thus other options should be investigated. In this study we aim to assess the effect of intensive-lifestyle-modification(ILM) with or without Liraglutide-3mg daily versus sleeve-gastrectomy(SG) on BMI at 1-year.
Subjects/Methods: In this study performed in a University Hospital in Italy, non-diabetic patients eligible for bariatric-surgery are recruited from the weight loss clinic and have the option to choose within three possible weight-loss programs up to complete the allocation of 25 subjects in each arm matched by BMI and age. ILM consists in 600kcal very-low-calorie-diet(VLCD) for 1 month followed by 12kcal/kgbw high-protein, high-fat-diet for 11 months plus 30minutes brisk-walk daily and at least 3 hours aerobic-exercise weekly. SG patients have 1-month VLCD and free-diet thereafter. Patients are evaluated at baseline and at 1,3,6,9 and 12months.
Detailed Description
Obesity is associated with major chronic diseases, including type 2 diabetes (T2D) and cardiovascular disease (CVD) 1-3. The number of subjects affected by morbid obesity or class III obesity (BMI≥40 kg/m2) is rapidly increasing 4 and contributed to 20% of the total per capita health-care expenditures in 2000 in the United States 5 .
Subjects with a body mass index (BMI) >40 kg/m2 or >35 kg/m2 in the presence of obesity complications are eligible for bariatric surgery 6 . The mortality rate after bariatric surgery is low, being 0.08% within 30 days and 0.31% after 30 days 7, and bariatric surgery has shown many health benefits including reduction of long term mortality 8 and type 2 diabetes remission (T2D) 9-11., However, due to the perception that bariatric surgery is a risky procedure among the general public and insurance companies or other health care providers only 1% of the clinically eligible subjects receive surgical treatment for their obesity 12.
The largest portion of patients eligible for bariatric surgery but who are not willing to be operated or cannot undergo surgery for other reasons should be offered, however, with other therapeutic options. To this end a pilot study to determine the efficacy of an intensive lifestyle modification (ILM) with or without 3 mg daily Liraglutide versus bariatric surgery with free diet and free physical activity was designed. In the medical arms the patients were also invited to contact the dietitian and the physician every week by email or by phone to assure a tight weight control. The allocation of the patients, all of them eligible for bariatric surgery, was on a voluntary basis, i.e. they were invited to decide their allocation in one of the 3 arms of the study matched by BMI and age.
Liraglutide, a glucagon-like peptide-1 analog, approved for the treatment of obesity at the dose of 3 mg per day and commercialized under the name of Saxenda, was proved to reduce body weight after 56 weeks by 8.4±7.3 kg as compared with a mean of 2.8±6.5 kg in the patients under placebo 13 . Importantly, the weight reduction is maintained up to 3 years as shown by LeRoux et al. 14.
However, this degree of weight loss is generally considered insufficient by patients who would like to be considered for bariatric surgery.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ranging from 18 to 70 years, stable body weight in the previous 6 months body mass index (BMI expressed in kg/m2) >35 if comorbidity (hypertension, sleep apnea, severe hip or knee arthritis) are present or >40 kg/m2.
Exclusion Criteria
- •Type 1 or 2 diabetes, previous bariatric surgery, a history of pancreatitis, a history of major depressive or other severe psychiatric disorders, a family or personal history of multiple endocrine cancer type 2 or familial medullary thyroid carcinoma.
Arms & Interventions
Lifestyle modification
1 month of a VLCD with 865 kcal per day followed by a 12 kcal per kg of body weight of a high-protein, high fat diet for 11 months in association with intensive
Intervention: lifestyle modification (Other)
Lifestyle modification plus Liraglutide 3 mg
1 month of a VLCD with 865 kcal per day followed by a 12 kcal per kg of body weight of a high-protein, high fat diet for 11 months in association with intensive. The patients will also receive Liraglutide 3 mg daily sc.
Intervention: LIRAGLUTIDE 3 Mg/0.5 mL (18 Mg/3 mL) SUB-Q PEN INJECTOR (ML) (Drug)
Lifestyle modification plus Liraglutide 3 mg
1 month of a VLCD with 865 kcal per day followed by a 12 kcal per kg of body weight of a high-protein, high fat diet for 11 months in association with intensive. The patients will also receive Liraglutide 3 mg daily sc.
Intervention: lifestyle modification (Other)
Sleeve Gastrectomy
The patients will undergo laparoscopic sleeve gastrectomy
Intervention: sleeve gastrectomy (Other)
Outcomes
Primary Outcomes
Change of baseline BMI
Time Frame: 1 year
percent variation of BMI with respect to baseline value
Secondary Outcomes
- changes of baseline weight plasma(1 year)
- changes in HOMA-IR(1 year)
- changes in blood pressure(1 year)
- changes in lipid profile(1 year)
- changes in body composition(1 year)
- changes in plasma glucose(1 year)
Investigators
Geltrude Mingrone
Principal Investigator
Catholic University of the Sacred Heart