Obesity is a serious rapidly increasing health problem with long term major effects [24,25]. It was a must to find new procedures to prevent and treat obesity [26]. Currently, bariatric surgery is the most effective treatment for extreme obesity [27]. But unfortunately associated with a lot of complications both short and long term [28,29]. Techniques for treating obesity using bariatric endoscopy are developing, including intra-gastric balloons, gastroplasty, malabsorptive treatments, endo-luminal devices, and injections of chemicals that delay gastric movement and emptying [30-32]. New pharmacological therapies are now investigated to solve the problem of obesity.
Previous research supported the involvement of antral contractility in regulating the proper evacuation of solid meals from the stomach [33]. Reduced gastric antrum contractility results in a longer half-time (T1/2) of stomach emptying, a longer lag period, and a slower post-lag gastric-empting stage [34]. BTA causes cholinergic transmission to be inhibited, which reduces the intestinal tract's contractility [35]. With doses ranging from 100 to 300 U, BTA injection is used to treat achalasia, anal fissure, diffuse esophageal spasm, and anismus [36].
Unfortunately, BTA's effects are reversible because, according to the majority of research done on achalasia patients, the effects of injections endure for seven months [37]. The use of BTA for long-term therapy of obesity may be constrained by the reversible effect. However, temporary weight reduction may be advantageous for those who need surgery or who are motivated to alter their eating and exercise routines after losing weight. Additionally, some people may need to have BTA injections on a regular basis.
Regarding the physiologic effects of stomach BTA injections in obese people, conflicting results are known [5-9,38]. Although a randomised, placebo-controlled trial using a dose of 200 U BTA revealed increased satiety, delayed gastric emptying, decreased gastric capacity in response to meal, and calculated weight loss when compared to saline control, most open-label studies and two randomised trials exploring doses of 100 to 300 U showed little effect of gastric BTA injections [11].
Results of these studies don’t depend on dose of BTA only but also depth of injection in the wall of stomach. In our study we used EUS to confirm injection into muscularis propria by passing the needle to subserosa then gradual withdrawal.
EUS guidance of BTA injection clarifies the site at which BTA is deposited and may double its efficacy.
Also, we used 100 U of BTA as it is a safe dose previously used for the treatment of anal fissure and achalasia [39]. But the antral muscle is a more voluminous structure than the lower esophagus and anal sphincter. In a study by Topazian et al. (2008), decrease in mean body weight was the same in both groups either who received 100 U or those received 300 U (5.0 vs. 4.8 kg). There was decreased gastric emptying in three subjects who received 300 U BTA but with no more body weight loss.
Possible reasons for increased satiety include delayed gastric emptying, a smaller antrum's capacity, which increases the feeling of intragastric contents, BTA's ability to inflame the antrum, changes in the secretion of gastric hormones (such as gastrin, ghrelin, or somatostatin), or a placebo effect [7].
We observed that the 16-week trial period continued the steady loss of body weight, and satiation increased at 16 weeks compared to baseline. Although similar protracted responses to BTA have been described in the treatment of achalasia, the apparent sustained efficacy of antral muscularis BTA goes beyond the presumptive duration of action of BTA in skeletal muscle [40]. The cause of these ongoing benefits at 16 weeks is unknown, but it may be related to a biological effect of BTA on gastrointestinal smooth muscle that lasts longer than its effects on skeletal muscle, inflammation caused by BTA injection (such as myenteric ganglionitis), a behavioural benefit of BTA injection that lasts after the pharmacological benefit has subsided, or a placebo effect. It is obvious that more research is necessary.
Liraglutide, sold under the brand names Saxenda® and Victoza®, is a glucagon-like peptide-1 (GLP-1) receptor agonist. The FDA initially approved Victoza®, a 1.8 mg subcutaneous injection of liraglutide, as a treatment for the management of type 2 diabetes in 2010. Clinical trial outcomes demonstrated GLP-1 analogues' capacity to promote weight loss. Saxenda® (liraglutide 3.0 mg daily subcutaneous injection) is the newest FDA-approved medication for chronic weight management in patients with obesity or who are overweight with a BMI 27 kg/m2 and have a weight-related comorbid state. This is because liraglutide was also developed as a weight loss agent. Its 3.0 mg daily dose [41].
The effects of GLP-1 on weight loss are assumed to be caused by delayed stomach emptying and decreased appetite [42].
Our study showed that there was significant weight reduction in GLP-1 group from (123.28±17.17 kg) to (109.75±14.37 kg) after 4 months (p <0.001) who continued throughout the study. Mean weight reduction was 10.9%. In agreement with our study, According to the SCALE Obesity and Prediabetes trial, more patients in the liraglutide group than in the placebo group lost at least 5 percent and 10 percent (33.1 percent and 10.6 percent, respectively) of their starting weight [43].
Also, in our study there was a significant reduction of mean BMI in GLP-1 RA group from baseline value (44.15±5.94 kg/m2) to (39.40±5.68 kg/m2) after 4 months. Waist circumference was also reduced significantly from (114.05±11.67 cm) to (106.75±10.71 cm) after treatment. These results are coping with that determined by The SCALE Obesity and Prediabetes trial; the liraglutide group had a significant decrease in the mean BMI, waist circumference as compared with placebo [43].
Liraglutide typically improved quality of life and was well tolerated. The majority of adverse events were mild or severe. Consistent with the known physiological effects of GLP-1, gastrointestinal symptoms (especially nausea and vomiting) occurred more frequently than with placebo. Liraglutide 3.0 mg was linked to increased weight loss at year 1, although even those who did not suffer these side effects lost more weight than those on a placebo or orlistat. that is what concluded by [44]. In our study one subject in GLP-1 RA group reported nausea, vomiting and diarrhea when reached the dose 3mg/d which were controlled by reducing the dose.