Obesity is a growing health concern in Iran and is now a global pandemic. The latest World Health Organization (WHO) report on obesity indicates that the overweight and obese population is growing. In fact, the prevalence of obesity has nearly doubled worldwide since 1980, and more than 10% of the world’s adult population is obese [1]. Although the obesity prevalence remained unchanged during the last 10 years in the United States [2], it is still high: 35.5% of the adult population in the United States is obese, which is defined as a body mass index (BMI) ≥30, 15.5% have a BMI over 35, and 6.3% are morbidly obese (BMI ≥40) [3]. Obesity prevalence is on the rise in developing countries due to demographic, socioeconomic, and nutritional transitions [4], and Iran is no exception: 10.8% and 3.4% of the population are obese and morbidly obese, respectively [5].

Severe obesity is associated with comorbidities such as type 2 diabetes mellitus, hypertension, cardiovascular disease, degenerative joint disease, and sleep apnea [6,7]. It has a major impact on quality of life [8] and psychosocial health as well, and major depression is seen in 7% of this population [9].

Over the past few decades, there has been a major change in trends of obesity treatment. Lifestyle modifications can, at best, induce a 5-10% weight loss and improve obesity-related morbidities to a limited extent [10]. However, advancements of bariatric surgery in less invasive and safer techniques, along with the evidence-supported superior results over lifestyle modifications, rendered surgery a better treatment option [11-13]. A recent meta-analysis found a 26 kg weight difference between surgical versus non-surgical treatment of morbidly obese patients in 1-2 years follow-up [14]. A Utah obesity study found this difference at 27% of initial body weight between the two groups after 6 years [15]. Results of the Swedish Obese Subjects study after 20 years of follow-up showed 18% mean weight loss for the surgical group, compared with 1% for the non-surgical [16]. Another meta-analysis including 161,756 patients showed BMI loss of 12-17 kg/m² after 5 years following bariatric surgery [17]. Overall, evidence now supports the choice of bariatric surgery over lifestyle changes for the treatment of severe obesity not only because of excess weight loss (EWL) reductions, but also because of significant benefits in terms of comorbidities and prolonged survival [13,18,19]. However, surgery is not without risks; perioperative mortality is estimated about 0.3%, and 30-day complication rate about 4.1% [20].

There are various surgical procedures for the treatment of severe obesity. Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), and biliopancreatic diversion with or without duodenal switch (BPD/BPD-DS) are the recommended and most commonly performed today [21]. Laparoscopic procedures are in general preferred over the open approach [11]. Newer techniques such as plication and mini-gastric or single loop gastric bypass are also emerging. Besides the variable effectiveness across procedures, each has risks and benefits.

In terms of effectiveness, since no single study has incorporated all the techniques, inference must be made through pooled data analyses. In general, BPD/BPD-DS results in more EWL (especially for patients with a very high BMI). RYGB and LSG have shown somewhat comparable results, although some studies have shown a significant advantage for RYGB [22]. LAGB comes after these techniques. Their effect on improvement of comorbidities follows the same order [23,24].

In terms of complication rate and safety, some studies have shown a significant difference between procedures. A meta-analysis of 85,048 patients found a 30-day mortality of 1.11% for BPD-DS, 0.16% for RYGB, and 0.06% for AGB [25]. Another study evaluating LSG found its rate between LAGB and RYGB to be 0.11%, 0.05%, and 0.14% respectively [22]. Overall complication rate is estimated between 4-25% [26]. Most common adverse effects after bariatric surgery are iron deficiency anemia after bypass operations (15%) and reoperations (8%) [14]. RYGB, among others, is associated with higher complication rates, while LAGB showed more reoperation rates, up to 35% according to a large cohort study [27].

There is still no universal agreement to recommend one procedure over another. Choice of the procedure depends on many factors such as the available expertise, risk stratification, patient preferences, and goal of therapy (weight loss vs glycemic control) [25].

We aim to undertake a prospective study evaluating and comparing several surgical bariatric procedures in an Iranian population of morbidly obese patients presenting to a specialized bariatric center. As newer techniques such as LSG (as a stand-alone operation) and mini-gastric bypass are emerging and gaining popularity, their role in bariatric surgery needs to be evaluated before incorporation into general practice.

This is one of the very first studies of its kind in the Middle East and addresses the knowledge gap on the effectiveness, safety, and efficacy of bariatric surgical techniques, including LSG, mini-bypass, and gastric plication [28].

The main objectives of the study are to identify perioperative problems of morbidly obese patients; to assess and compare the effectiveness of different bariatric surgical techniques on metabolic syndrome and other obesity-related comorbidity, by measuring anthropometric indices, EWL rates, glucose homeostasis, blood pressure, lipid profile, hormone levels, and nutritional status; to assess the psychosocial aspects of obesity before and after the bariatric surgery, and long term, including quality of life and depression; and to explore the mechanisms and underlying pathophysiology in the field of obesity and its comorbidities through pathological, genetic, and molecular studies. The study variables are summarized in Table 1.

Tehran Obesity Treatment Study (TOTS) is an ongoing, single-institution, prospective study commencing March 2013. The TOTS enrolls patients to undergo a bariatric procedure based on an individualized clinical decision plan. It is organized into 4 phases: preoperative evaluation, operation, short-term follow-up, and long-term follow-up.

Severely obese patients presenting to the Tehran Obesity Treatment Center are examined by an obesity expert in the clinic to evaluate whether they meet the study inclusion criteria. Patients then attend a free-of-charge monthly comprehensive seminar in order to increase their awareness on the subject and promote active participation in the treatment plan. After providing written informed consent, patients proceed with individualized comprehensive sessions and decisions about suitability of surgery and the specific technique are made.

Inclusion criteria were 15-65 years old, BMI levels ≥40 kg/m² or 30<BMI<35 kg/m² with a medical comorbidity/failure of intensive medical treatment for at least 1 year, acceptable surgical risk, and able and willing to provide informed consent and assure regular follow-up.

Exclusion criteria were obesity due to a treatable medical disease (eg, endocrine abnormality); any other medical, psychological, or social condition which, in the opinion of the investigators, would interfere with safe completion of the study protocol; high operative risk; contraindication to bariatric surgery or weight loss; active drug addiction; nursing, pregnant, or intending to become pregnant in the following year; and unable or unwilling to complete questionnaires or expected to experience difficulty with attendance of visits or completion of study.

Bariatric procedures that are performed in this study include RYGB, LAGB, LSG, and mini-gastric bypass. Newer techniques such as gastric plication are also considered as a treatment option in suitable candidates. In order to record all aspects of the procedures from pre-op to postop, we broke down each of the surgical procedures into its components (eg, length of alimentary limb, pouch size) and structured a measuring scheme.

A single surgical team will perform all operations under general anesthesia, with the patient in the supine position. A standard 5-port laparoscopic technique with the bed in the reverse Trendelenburg position is used. Patients not suitable for laparoscopy will undergo a traditional laparotomy (see Multimedia Appendix 1).

An electronic database for precise data collection was designed. Manuals of operations and procedures were also created to minimize technical variability. Data collectors including study investigators and surgeons underwent training and certification with respect to study protocols. Quality control procedures including frequent contacts and visits between the surgeon and clinical center staff help to ensure complete and accurate data collection. Investigators used validated and standardized instruments for objective and subjective measures. When not available, new instruments were created to meet the specific goals of the study (see Multimedia Appendix 1).

A brief summary of each outcome domain and standard forms and measures used to assess each of these domains, as well as the contact points at which they will be administered, are described below.

This study has been approved by the Human Research Review Committee of the Endocrine Research Center, Shahid Beheshti University of Medical Sciences, No. 2ECRIES 93/03/13.