A comprehensive review examined current and emerging treatment options for obesity, highlighting the safety and efficacy profiles of various medical, endoscopic, and surgical approaches.
In the review, published in the Journal of Translational Gastroenterology, investigators covered a range of treatments, from older options like orlistat to newer pharmacologic interventions. They determined that orlistat combined with lifestyle changes contributed to a weight reduction of 5.8 kg compared with 3.3 kg with placebo over 4 years. However, newer treatments showed greater efficacy.
Glucagon-like peptide-1 (GLP-1) receptor agonists demonstrated significant weight loss effects. A 68-week study showed weekly subcutaneous semaglutide 2.4 mg achieved a mean weight loss of 15.4% compared with 6.4% with daily subcutaneous liraglutide 3.0 mg. In a 26-week trial, comparing oral semaglutide 14 mg to subcutaneous liraglutide 1.8 mg in patients with diabetes, placebo-subtracted average weight losses were 4.2% and 2.7%, respectively.
Combination therapies exhibited enhanced efficacy. The pramlintide-phentermine combination resulted in a 10.5% weight reduction after 24 weeks compared with 2.5% for pramlintide alone. Phentermine-topiramate combination therapy achieved placebo-subtracted weight losses of 3.5% at low doses and 9.3% at higher doses. Naltrexone/bupropion combination therapy showed average placebo-subtracted weight losses of 3.7% at 16/360-mg and 4.8% at 32/360-mg doses.
Surgical interventions remained highly effective. A 3-year randomized controlled trial (RCT) comparing laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) found similar efficacy in reducing excessive body mass index and improving quality of life. A 7-year follow-up study revealed LRYGB resulted in higher mean percentage excess weight loss (55%) compared with LSG (47%), with a 4.6% higher total morbidity rate.
Metabolic effects differed between surgical procedures. LSG was associated with more altered lipid metabolites and changes in amino acid metabolism, whereas LRYGB showed alterations in bile acids. Both procedures decreased triglyceride-rich lipoproteins through different mechanisms.
Emerging endoscopic procedures offered minimally invasive alternatives. Transcatheter bariatric embolization (TBE) demonstrated a total body weight loss of 7.4 kg (6.4% reduction) compared with 3.0 kg (2.8% reduction) with sham procedure at 6 months. Endoscopic sleeve gastroplasty (ESG) achieved a 53% reduction in excess body weight at 6 months, with a 59% decrease in caloric intake to reach gastric fullness.
The primary obesity surgery endoluminal (POSE) procedure, an endoscopic incision technique, showed promise. A study reported that 79% of patients who underwent POSE procedures had a mean percent excess weight loss of approximately 50% after 1 year with no development of any serious side effects.
Intragastric balloon (IGB) therapy showed efficacy in class I and II obesity. A pooled analysis of seven RCTs revealed percent total body weight losses of 7.4% to 14.9% in patients who received IGB therapy compared with 2.4% to 5.4% in patients who received standard care at 6 to 8 months. IGB use was associated with improvements in metabolic parameters, including reductions in metabolic syndrome (34.8% to 11.6%), type 2 diabetes (32.6% to 21.3%), hypertriglyceridemia (37.7% to 17.4%), hypercholesterolemia (33.4% to 18.9%), and hypertension (44.9% to 34.8%) at 12 months postremoval.
The endoluminal duodenal-jejunal bypass liner (DJBL) procedure resulted in a 15% reduction in total body weight and a 0.6% reduction in HbA1c at 12 months in patients with class I obesity and long-term type 2 diabetes mellitus. An RCT found 24% of the patients who received the DJBL procedure achieved ≥ 15% body weight reduction compared with 4% in the control group at 12 months.
Adverse events were reported across interventions. IGB procedures were associated with gastrointestinal perforation (0.3%), esophageal mucosal injury (0.8%), and gastric ulcer/bleeding (0.76%). DJBL procedures reported major side effects in 9.5% of patients, including severe abdominal pain and acute cholecystitis with duodenal fistula.
The review also noted emerging approaches, including probiotics and herbal supplements. Studies on Lactobacillus reuteri and Saccharomyces boulardii showed promising results in animal models, with potential applications in human weight management.
The investigators emphasized that current evidence-based practices for obesity management involve multimodal approaches, including lifestyle modification, mechanical gastric restriction, modulation in the secretion of multiple gut hormones, alteration in the composition and secretion of bile acids, and alterations of the gut microbiome.
The review concluded that while several novel endoscopic devices and procedures showed promise because of their satisfactory results, relatively lower cost, and lower risk, further studies assessing their safety, effectiveness, and sustainability are warranted.
The authors had no conflict of interests related to this publication.
