v
Search
Advanced Search

Publications > Journals > Journal of Translational Gastroenterology > Article Full Text

  • OPEN ACCESS

Obesity and Current Treatment Approaches: A Comprehensive Review

  • Karthik Mathialagan1,
  • Madhumitha Rondla2,
  • Karthik Muralidharan1 and
  • Sun-Joo Jang1,* 
 Author information
Journal of Translational Gastroenterology   2024;2(1):30-37

doi: 10.14218/JTG.2023.00040

Abstract

Obesity is a global health burden and is closely associated with severe chronic co-morbidities, which remain the leading causes of death. Significant progress has been made in the treatment of hypertension, diabetes, and hyperlipidemia over the last half-century. However, advancements in the management of obesity have been slow, with some medications exhibiting inadequate efficacy and dangerous side effects. Improved understanding of the gut-brain axis has inspired the pursuit of novel medications aiming to provide sustainable and safe weight loss. Current evidence-based practices for obesity management involve multi-modal 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. Each physician is responsible for recognizing obesity as a disease and assisting patients in appropriate management based on strong evidence and a good safety profile, aligned with the patient’s goals. Through this review, we aim to inform the readers of recent approaches for managing obesity and comparing their beneficial effects and efficacy on obesity and its long-term co-morbidities.

Keywords

Obesity, Weight loss, Bariatric surgery, Glucagon like peptide 1, Orlistat, Probiotics, Intragastric balloon, Endoscopy

Introduction

The relationship between diet and chronic diseases such as hypertension, diabetes, colon cancer, and obesity has undergone extensive investigation, supported by a large number of data, indicating a causal relationship between them. Globally, mortality has shown strong associations with diets low in whole grains, high in sodium, and low in fruits.1 Recent increases in obesity rates have been attributed to unhealthy eating habits and food choices leading to excessive energy intake.2 Many studies have recognized the positive correlations between energy density, weight, and other markers of metabolic syndrome.3 The problem of obesity or overweight accounts for two-thirds of the U.S. population. Obesity, a global health burden, is associated with comorbidities, such as diabetes mellitus, coronary artery disease, hypertension, and other systemic health issues, which are the leading causes of death.4 In the modern era, obesity is typically defined as a body mass index (BMI) ≥30 kg/m2, while a BMI value of 25–29.9 kg/m2 is classified as overweight. Dietary factors, lifestyle, genetics, and environmental factors significantly contribute to obesity. A recent analysis revealed a near doubling of worldwide obesity prevalence since 1985, affecting half a billion people worldwide, and accounting for 4 million deaths annually worldwide.5 However, the awareness of available therapeutic options remains low, prompting us to provide insights into these options through this article.

Obesity has significant effects on the gastrointestinal system. It contributes to esophageal diseases through both mechanical and humoral factors, with proinflammatory cytokines playing a crucial role in other digestive diseases.6 Munch et al. demonstrated in an experiment on L2-IL1B mice (a transgenic mouse model of Barrett’s esophagus) that a high-fat diet accelerated esophageal dysplasia by enhancing local pro-inflammatory immune responses and altering intestinal microbiota, irrespective of body weight.7 Lower esophageal sphincter abnormalities, increased risk of hiatal hernia, and increased intragastric pressure are other mechanical causes of obesity directly influencing Barrett’s esophagus and adenocarcinoma.6 Obesity is also an important risk factor for colorectal adenoma and cancer. Several factors contribute to the increased risk of colon cancer in individuals with obesity, including alterations in systemic growth factors, visceral adipose tissue, the microbiome, bile acids, inflammation, and a diet rich in fat, sugar, high fructose corn syrup, or low vitamin D.8 Studies have indicated that visceral adipose tissue may lead to higher circulating levels of insulin growth factor through worsening insulin resistance, thereby increasing the risk of carcinogenesis.6 Furthermore, a high-fat diet induces colon and intestinal tumorigenesis by promoting the proliferation of intestinal stem cells.9

Multiple modalities, 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, have been explored in obesity management.10 Previous studies have primarily focused on pharmaceutical therapies, including combination therapies using different medical or interventional therapies with multiple targets for treating obesity.11 Recently, bariatric surgical procedures have been extensively adopted and demonstrated efficacy in treating obesity.12 As the prevalence of obesity increases, novel therapeutic approaches such as probiotics,13,14 laparoscopic surgery,15 topical lotions and subcutaneous medication,16,17 transcatheter bariatric embolization,18 low insulin method,19 or gene therapy20 have gained attention.

This comprehensive review aims to consolidate the recently applied medical, endoscopic, and surgical approaches for managing obesity and compare their beneficial effects and efficacy on obesity and its long-term comorbidities. We particularly aim to highlight newer experimental techniques for the management of obesity, including transcatheter bariatric embolization, intragastric balloon therapies, primary obesity surgery endoluminal procedures, and the Endobarrier procedure, which have shown promise in recent studies.

Medical management

Glucagon-like peptide 1 agonist

Long-acting glucagon-like peptide 1 (GLP-1) agonists such as semaglutide, liraglutide, and tirzepatide are currently available in the U.S. for the management of obesity, especially in patients with impaired glucose tolerance.21,22 The primary outcome of a recent study indicated that the mean weight loss with weekly subcutaneous injections of semaglutide 2.4 mg was 15.4% at week 68, compared to a mean weight loss of 6.4% in those receiving daily subcutaneous liraglutide 3.0 mg.23 Another analysis compared daily oral semaglutide 14 mg with daily subcutaneous liraglutide 1.8 mg for obesity management in diabetic patients whose glycemic indicators were stable on metformin. The outcomes indicated a placebo-subtracted average weight loss of 4.2% with oral semaglutide compared to a placebo-subtracted mean weight loss of 2.7% with subcutaneous liraglutide at the end of the 26th week.24 Thus, whether administered orally or subcutaneously, semaglutide appears to be superior to subcutaneous liraglutide for the management of obesity. Figure 1 shows a comparison of the results from these two studies. Tirzepatide is a newer dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist.25 Although trials comparing the efficacy of tirzepatide and other GLP-1 are still underway, recent studies have demonstrated encouraging outcomes. An open-label, 40-week, phase III randomized trial comparing weekly tirzepatide and semaglutide in type 2 diabetes mellitus patients indicated that reductions in body weight were greater and statistically significant with tirzepatide than with semaglutide in the secondary endpoints.25 A more recent phase III placebo-controlled, double-blind, randomized trial comparing percentage weight loss for three different doses of weekly tirzepatide showed a significant and sustained reduction in weight, with a higher percentage of weight loss observed with higher doses.26

Outcome efficacy of semaglutide and liraglutide.
Fig. 1  Outcome efficacy of semaglutide and liraglutide.

The left graph shows the mean percent weight loss (%WL) at week 68 by comparing weekly subcutaneous semaglutide to daily subcutaneous liraglutide. The right graph shows the mean percent weight loss (%WL) at week 26 by comparing daily oral semaglutide to daily subcutaneous liraglutide. %WL, percent weight loss.

Orlistat

Orlistat is a reversible inhibitor of gastrointestinal lipases, traditionally employed for obesity management.21,22 Orlistat, combined with lifestyle changes, contributed to a reduction in weight by 5.8 kg compared to 3.3 kg with placebo over 4 years.27 A 37.3% reduction in the risk of diabetes mellitus was observed in patients treated with orlistat vs. placebo. Orlistat has an excellent long-term safety profile, and serious adverse events are rare.28 Despite this, a high rate of gastrointestinal side effects such as oily stools, diarrhea, abdominal pain, and fecal spotting, as well as interactions with several drugs affecting their bioavailability and effectiveness, limits adherence and makes it a less popular option.29

Lorcaserin

Lorcaserin is a serotonin 2C receptor agonist. Research indicates that it contributes to a reduction in body weight of 5.8 kg in 47.5% of the subjects over a year, compared to a weight reduction of 2.2 kg in 20.3% of the subjects in the placebo group. Weight loss was sustained in a significantly greater number of patients in the Lorcaserin group during the second year.30 The CAMELLIA–TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients–Thrombolysis in Myocardial Infarction 61) investigated the long-term cardiovascular safety and efficacy of lorcaserin in obese or overweight patients with cardiovascular disease or risk factors. The rates of several cardiovascular and metabolic risk factors, such as blood pressure, heart rate, low density lipoprotein, and triglycerides were slightly lower in the intervention group than in the placebo group. At one year, the rate of cardiovascular events was similar in both groups.31 A safety review of this study also identified a potential signal for increased cancer incidence, however, the study was not powered for cancer end-points.32 A review conducted by the Food and Drug Administration (FDA) in 2020, based on a large post-marketing clinical trial revealed a higher frequency of cancer diagnosis for 13 types of cancer, including colorectal cancer, pancreatic cancer, and lung cancer, in the lorcaserin group compared to the placebo group.32 Consequently, the FDA requested manufacturers to voluntarily withdraw their products from the market due to these safety concerns.

Combination therapies

Combination pharmacotherapy is increasingly being adopted worldwide for obesity treatment due to its heightened efficacy and beneficial outcomes.21 The combined implication of pramlintide and phentermine was found to be eight times more efficacious than pramlintide monotherapy in reducing human weight. This combined pharmacotherapy resulted in a weight reduction of approximately 10.5%, compared to 2.5% for pramlintide alone after 24 weeks.11 Exenatide once weekly, combined with daily dapagliflozin, induced greater weight reduction than either of the individual therapies, with results sustained over a year, suggesting long-term sustainable benefits in weight reduction.11 The combination of phentermine and topiramate resulted in an overall placebo-subtracted weight loss of 3.5% at low doses and 9.3% at higher doses. Major studies leading to the approval of naltrexone/bupropion reported an average placebo-subtracted weight loss of 3.7% at a dose of 16/360 mg, and 4.8% at a dose of 32/360 mg.33 Similarly, co-infusion of sub-anorectic doses of GLP-1 and glucagon demonstrated a 13% reduction in food intake34 while simultaneously increasing energy expenditure, thus improving obesity and glycemia.35 Therefore, combination therapies are not only more efficacious in treating obesity but also have more long-lasting effects than monotherapies. Some of the commonly prescribed medications for the management of obesity are summarized in Table 1.

Table 1

Commonly prescribed medications for obesity management

Drug ClassGeneric NamesDosesComments
Glucagon-like Peptide 1 agonistSemaglutideStart with 0.25 mg subcutaneous (SC) once a week. Increase the dose every 4 weeks by 0.25 mg till a maximum of 2.4 mg is reached.Monitor for eye complications in patients with Diabetic retinopathy.
LiraglutideStart with 0.6 mg SC daily and increase at weekly intervals by 0.6 until maximum 3 mg.
TirzepatideStart with 2.5 mg weekly and increase by 2.5 every 4 weeks to maximum 15 mg.Currently approved for type 2 diabetes and obesity management.
All: Hypoglycemia if co-administered with other diabetes medications. Rarely reported: pancreatitis. Contraindicated in pregnancy and patients with a family history of medullary thyroid cancer (based on murine models) or multiple endocrine neoplasia.
Gastric/pancreatic lipase inhibitorsOrlistat120 mg TID with fat containing meals (60 mg TID for those who cannot tolerate 120 mg).Good safety profile for long-term use. GI side effects could be the limiting factor.
Combination TherapiesPhentermine and TopiramateStart with 3.75 phentermine and 23 mg topiramate daily for 14 days, increase by 3.75/23 for 12 weeks. Then increase based on response to a maximum of 15/92.Phentermine has abuse potential. Side effects include dry mouth, paresthesia, cognitive deficits, anxiety, insomnia, etc. Contraindicated in pregnancy (note topiramate is teratogenic), hyperthyroidism, glaucoma, and co-administration with MAO inhibitors.
Naltrexone and bupropionStart with 8 mg naltrexone and 90 mg bupropion daily (1 combination pill). Increase by 1 pill every week to a maximum of 4 tablets daily.Nausea, vomiting, insomnia, dry mouth, increase in blood pressure. Contraindicated in poorly controlled hypertension, seizure disorder, opioid use disorder, opioid agonist therapy, pregnancy, and breastfeeding.
Noradrenergic sympathomimeticsphentermine15 mg to 37.5 mg daily.Several side effects and usually avoided unless it is short term only (<12 weeks).

Probiotics

Probiotics can modify gut microbiota and have been shown to contribute to body weight reduction in experimental animal studies. In an 8-week-old Apoe knock-out mouse model, the group of mice receiving Lactobacillus reuteri strain ATCC PTA 4659 indicated a significant reduction in body weight, adipose, and liver weight, and decreased serum insulin levels, attributing to increased β-oxidation.13 Another study demonstrated that the oral administration of Saccharomyces boulardii over 4 weeks resulted in a 15% reduction in body weight gain, accompanied by a significant decrease in whole-body fat mass, without altering food intake in a mouse model.14 Additionally, supplementation with S. boulardii and superoxide dismutase for 60 days in obese population led to significant weight loss and fat loss, while preserving fat-free mass in a randomized clinical trial (RCT).36

Herbal supplements

The use of herbal weight loss supplements has recently attracted increased amounts of attention due to the increasing prevalence of obesity. Garcinia cambogia supplements containing hydroxycitric acid are marketed for weight loss;37 however, the FDA has recently issued a warning following post-marketing surveillance indicating an increased risk of hepatotoxicity associated with garcinia cambogia. Conjugated linoleic acid supplementation has shown limited evidence for weight loss, but studies have demonstrated an increase in oxidative stress and insulin resistance with regular consumption of conjugated linoleic acid, which limits its utilization.38 L-carnitine, an amino acid naturally produced in the liver and kidneys, is thought to aid in managing obesity through its effects on glycemic control and lipid-lowering activities. However, analyses have shown that it produces only a moderate effect on weight loss.39

Other novel medical approaches

There are several other promising medical approaches for the management of obesity. The administration of transforming growth factor beta superfamily ligands, including GDF15 and MIC-1, has been shown to reduce body weight and food intake in mouse and human models, respectively, making them advantageous in the treatment of obesity.40,41 Similarly, twice-daily topical application of a lotion containing aminophylline, caffeine, yohimbe, L-carnitine, and gotu kola, combined with exercise and restricted calorie intake for 28 days effectively reduced body mass, fat mass, and circumference in the treated area.16

Surgical management

The surgical approach for managing obesity has long been used to achieve sustainable results, especially in obese patients resistant to pharmacotherapy. Bariatric procedures are widely employed surgical interventions for treating obesity and its associated morbidities, consistently yielding desirable outcomes. Bariatric surgeries are considered the treatment of choice for patients with a BMI >40 kg/m2 or BMI >35 kg/m2 with severe associated comorbidities.10

Two major surgical approaches are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Figure 2 illustrates a compilation of studies comparing the post-surgical benefits and metabolic effects of LSG and LRYGB. Peterli et al. compared the post-surgical effects of LSG and LRYGB over 3 years in an RCT.15 The study concluded that both LSG and LRYGB groups demonstrated statistically equal efficacy in reducing excessive body mass index and improving quality of life up to 3 years after surgery. After 3 years, the improvement in co-morbidities was similar for both groups, except for dyslipidemia and gastroesophageal reflux disease, which responded more effectively to LRYGB treatment. Gronroos et al. performed another RCT comparing the post-surgical effects of LSG and LRYGB over a 7-year period.42 The results indicated that in a follow-up after 7 years, the mean percentage of excess weight loss was higher after LRYGB (55%) than after LSG (47%). Although LRYGB resulted in greater weight loss, it was associated with a 4.6% higher total morbidity rate. The long-term quality of life was similar after both procedures.

Outcomes of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB).
Fig. 2  Outcomes of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB).

The left graph shows the mean percent excess BMI loss (%EBMIL) between LSG and LRYGB at 3 years. The right graph displays the mean percent excess weight loss (%EWL) between LSG and LRYGB at 7 years. %EBMIL, percent excess body mass index loss; %EWL, excess weight loss; LRYGB, laparoscopic Roux-en-Y gastric bypass; LSG, laparoscopic sleeve gastrectomy.

In a study comparing the metabolic effects of LSG and LRYGB, the number of significantly altered lipid metabolites was higher following LSG than LRYGB, mainly due to anatomical differences between the two surgeries and factors related to gut microbiota.43 LSG was associated with alterations in amino acid metabolism, while LRYGB was associated with changes in bile acids. Studies conducted on triglyceride-rich lipoproteins (TRL) 6 months after surgery revealed that both TRL-apoB-100 and TRL-apoB-48 declined after LSG due to decreased production rates of both lipoproteins and an increased fractional catabolic rate of TRL-apoB-100 only. In contrast, the TRL-apoB-48 level did not significantly decrease after LRYGB.44

Laparoscopic vertical banded gastroplasty is another bariatric procedure effective in reducing body fat; however, it is less efficacious than LRYGB.45

Endoscopic management

As minimally invasive surgery is favored by patients, there has been significant development in endoscopic weight reduction procedures and devices. The major endoscopic procedures currently available are listed as follows:

Transcatheter bariatric embolization

Transcatheter bariatric embolization (TBE) uses a balloon micro-catheter to occlude the left gastric artery, thereby promoting weight loss. The LOSEIT study (The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial) was a randomized pilot study that established the proof-of-principle demonstrating that TBE is well-tolerated and effective in weight reduction.18 In the intention-to-treat population, total body weight loss was 7.4 kg with TBE (6.4% reduction) compared to 3.0 kg with sham (2.8% reduction) at 6 months after the procedure. Subjects treated with TBE had significant improvements in physical function, self-esteem, and overall quality of life at 6 and 12 months.

Endoscopic sleeve gastroplasty

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that effectively induces a reduction in body weight by decreasing the size of the gastric reservoir. Subjects who underwent ESG experienced a significant reduction in excess body weight of 53% at 6 months.46 In a physiological analysis, there was a 59% decrease in caloric intake to reach gastric fullness, along with decreased gastric emptying time for solids and increased insulin sensitivity.

Percutaneous gastrostomy devices

In a recent RCT by Thompson et al., an endoscopic device comprising an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage was utilized. The study demonstrated that 58.6% of participants in the intervention group lost 25% of their excess body weight, compared to 15.3% of participants in the control group. Notably, only 3.6% of the intervention group participants developed serious postoperative adverse effects.47

Primary obesity surgery endoluminal procedure

The primary obesity surgery endoluminal (POSE) procedure is an endoscopic incision procedure aimed to reduce the size of the stomach and decrease hunger cravings. A recent 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.48

Endoluminal endoscopic gastric jejunal bypass sleeve

Gastro-duodeno-jejunal bypass sleeve is a novel technique that serves as an alternative to bariatric surgery in patients with morbid obesity. It consists of a 120 cm long sleeve device, placed endoscopically to create an endoluminal bypass tract from the lower gastroesophageal junction to the jejunum. A prospective trial designed to study the effectiveness of endoluminal, endoscopic gastric bypass sleeve implants in morbidly obese individuals concluded that almost half of the participants experienced a mean percentage excess weight loss (EWL) of 54% after 12 months and sustained a mean %EWL of 30% at the 14-month post-explant follow-up, while the remaining required explantation or experienced partial cuff detachment before completing 1 year.49 This trial demonstrated that the gastro-duodenal-jejunal bypass sleeve could be an effective treatment option for the long-term management of morbid obesity.

Intragastric balloon therapy

Intragastric balloon (IGB) therapy has become an attractive tool for weight loss, owing to its sustained efficacy, low complication rate, and broad application, extending to class I and II obesity. This therapy involves a space-occupying device that alters gastric emptying and gastrointestinal neurohumoral pathways, leading to early satiety.50 Several different types of IGBs are commercially available in the U.S. Among patients with a BMI range of 30–40 kg/m2, IGB has shown superior outcomes in terms of weight loss compared to lifestyle modification alone. IGBs lead to greater weight loss at 6, 9, and 12 months after initial balloon placement; however, the amount of weight loss decreases during each successive time-period.51 A pooled analysis of 7 RCTs revealed that the percent total body weight loss (%TBWL) at the end of 6–8 months was 7.4–14.9% for patients with IGB compared to 2.4–5.4% for those receiving standard care.50

IGB use is associated with the improvement in various metabolic parameters and medical conditions compared with noninvasive measures for weight loss.51 IGB decreased the incidence of metabolic syndrome from 34.8% (pre-IGB) to 11.6% at 12 months post-IGB removal. The incidences of type 2 diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, and hypertension decreased from 32.6%, 37.7%, 33.4%, and 44.9% (pre-IGB) to 21.3%, 17.4%, 18.9%, and 34.8% respectively at 12 months post IGB removal.52 Among patients undergoing bio-enteric IGB placement, the prevalence of hypertension, diabetes, hypercholesterolemia, and osteoarthropathy decreased from 29%, 15%, 32%, and 25% (pre-IGB), respectively, to 16%, 10%, 21%, and 13% at 3 years post-IGB removal.53 Device intolerance (sense of fullness) and symptomatic intolerance (including epigastric pain, reflux, nausea, or emesis) remain the primary reasons for early IGB removal, occurring in approximately 9.4% of patients. More serious adverse events, such as gastrointestinal perforation (0.3%), esophageal mucosal injury (0.8%), gastric ulcer/bleeding (0.76%), and gastric outlet/bowel obstruction (0.12%), are relatively rare. No mortality was reported during the 6–8 month period following balloon placement.51

Endoluminal duodenal-jejunal bypass liner (endobarrier) Procedure

The application of endoluminal duodenal-jejunal bypass liner (DJBL), commonly referred to as endobarrier, has demonstrated effectiveness in managing chronic morbid obesity.54 In patients with class I obesity and long-term type 2 diabetes mellitus, the DJBL procedure resulted in a 15% reduction in total body weight and a 0.6% reduction in Hb1Ac at 12 months. Only 9.5% of the patients with the DJBL procedure experienced major side effects, including severe abdominal pain in one patient and acute cholecystitis with duodenal fistula due to bulbar transmural penetration and gall bladder impaction by one of the anchors.54 In an RCT for DJBL in patients with type 2 diabetes mellitus and obesity, 24% of the patients in the DJBL group achieved a ≥15% reduction in body weight compared to 4% in the control group at 12 months. DJBL demonstrated superior reductions in serum cholesterol, systolic blood pressure, and alanine transaminase levels at 12 months, while there was no significant difference in glycemic control.55

Duodenal mucosal resurfacing

Duodenal mucosal resurfacing (DMR) is a minimally invasive endoscopic procedure for circumferential hydrothermal ablation. DMR, particularly when combined with hypocaloric intake, has long-lasting efficacy in controlling diabetes and reducing both intramyocellular and intrahepatocellular lipids, while favoring the mobilization of abdominal fat and improving glycemia.56

Conclusions

Obesity has been a primary target for medical and surgical therapy. Various monotherapy options, such as GLP-1 agonists, have shown success in reducing weight. The combination pharmacotherapies have demonstrated significantly greater efficacy in weight loss compared to the individual drugs. Bariatric surgical methods provide more effective and long-lasting outcomes and carry a relatively higher risk of complications, which limits their widespread adoption. Several novel endoscopic devices and procedures are promising due to their satisfactory results, relatively lower cost, and lower risk. Further studies assessing the safety, effectiveness, and sustainability of these novel endoscopic techniques are warranted.

Abbreviations

BMI: 

body mass index

ESG: 

endoscopic sleeve gastroplasty

EWL: 

excess weight loss

FDA: 

food and drug administration

GLP-1: 

glucagon like peptide 1

IGB: 

intragastric balloon

LRYGB: 

laparoscopic roux-en-y gastric bypass

LSG: 

laparoscopic sleeve gastrectomy

POSE: 

primary obesity surgery endoluminal

TBE: 

transcatheter bariatric embolization

TRL: 

triglyceride rich lipoproteins

Declarations

Acknowledgement

None.

Funding

None.

Conflict of interest

The authors have no conflict of interests related to this publication.

Authors’ contributions

Study concept and design (KMa, MR and SJ), drafting of manuscript (KMa, MR), proofreading (SJ and KMu), critical revision of the manuscript (KMu).

References

  1. GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2019;393(10184):1958-1972 View Article PubMed/NCBI
  2. Smethers AD, Rolls BJ. Dietary Management of Obesity: Cornerstones of Healthy Eating Patterns. Med Clin North Am 2018;102(1):107-124 View Article PubMed/NCBI
  3. Vernarelli JA, Mitchell DC, Rolls BJ, Hartman TJ. Dietary energy density is associated with obesity and other biomarkers of chronic disease in US adults. Eur J Nutr 2015;54(1):59-65 View Article PubMed/NCBI
  4. Heymsfield SB, Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med 2017;376(3):254-266 View Article PubMed/NCBI
  5. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med 2017;377(1):13-27 View Article PubMed/NCBI
  6. Nam SY. Obesity-Related Digestive Diseases and Their Pathophysiology. Gut Liver 2017;11(3):323-334 View Article PubMed/NCBI
  7. Münch NS, Fang HY, Ingermann J, Maurer HC, Anand A, Kellner V, et al. High-Fat Diet Accelerates Carcinogenesis in a Mouse Model of Barrett’s Esophagus via Interleukin 8 and Alterations to the Gut Microbiome. Gastroenterology 2019;157(2):492-506.e2 View Article PubMed/NCBI
  8. Mana MD, Hussey AM, Tzouanas CN, Imada S, Barrera Millan Y, Bahceci D, et al. High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity. Cell Rep 2021;35(10):109212 View Article PubMed/NCBI
  9. van Driel MS, van Neerven SM, Vermeulen L. High-Fat Diet Impacts on Tumor Development in the Gut. Trends Cancer 2021;7(8):664-665 View Article PubMed/NCBI
  10. Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity: Pathophysiology and Management. J Am Coll Cardiol 2018;71(1):69-84 View Article PubMed/NCBI
  11. Camilleri M, Acosta A. Combination Therapies for Obesity. Metab Syndr Relat Disord 2018;16(8):390-394 View Article PubMed/NCBI
  12. Meneses E, Zagales I, Fanfan D, Zagales R, McKenney M, Elkbuli A. Surgical, metabolic, and prognostic outcomes for Roux-en-Y gastric bypass versus sleeve gastrectomy: a systematic review. Surg Obes Relat Dis 2021;17(12):2097-2106 View Article PubMed/NCBI
  13. Fåk F, Bäckhed F. Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice. PLoS One 2012;7(10):e46837 View Article PubMed/NCBI
  14. Everard A, Matamoros S, Geurts L, Delzenne NM, Cani PD. Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. mBio 2014;5(3):e01011-e01014 View Article PubMed/NCBI
  15. Peterli R, Wölnerhanssen BK, Vetter D, Nett P, Gass M, Borbély Y, et al. Laparoscopic Sleeve Gastrectomy Versus Roux-Y-Gastric Bypass for Morbid Obesity-3-Year Outcomes of the Prospective Randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS). Ann Surg 2017;265(3):466-473 View Article PubMed/NCBI
  16. Escalante G, Bryan P, Rodriguez J. Effects of a topical lotion containing aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola on thigh circumference, skinfold thickness, and fat mass in sedentary females. J Cosmet Dermatol 2019;18(4):1037-1043 View Article PubMed/NCBI
  17. Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA 2021;325(14):1403-1413 View Article PubMed/NCBI
  18. Reddy VY, Neužil P, Musikantow D, Sramkova P, Rosen R, Kipshidze N, et al. Transcatheter Bariatric Embolotherapy for Weight Reduction in Obesity. J Am Coll Cardiol 2020;76(20):2305-2317 View Article PubMed/NCBI
  19. Röhling M, Martin K, Ellinger S, Schreiber M, Martin S, Kempf K. Weight Reduction by the Low-Insulin-Method-A Randomized Controlled Trial. Nutrients 2020;12(10):3004 View Article PubMed/NCBI
  20. Angelidi AM, Belanger MJ, Kokkinos A, Koliaki CC, Mantzoros CS. Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy. Endocr Rev 2022;43(3):507-557 View Article PubMed/NCBI
  21. Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity. Endocr Pract 2016;22(Suppl 3):1-203 View Article PubMed/NCBI
  22. Son JW, Kim S. Comprehensive Review of Current and Upcoming Anti-Obesity Drugs. Diabetes Metab J 2020;44(6):802-818 View Article PubMed/NCBI
  23. Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA 2022;327(2):138-150 View Article PubMed/NCBI
  24. Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet 2019;394(10192):39-50 View Article PubMed/NCBI
  25. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021;385(6):503-515 View Article PubMed/NCBI
  26. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-216 View Article PubMed/NCBI
  27. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004;27(1):155-161 View Article PubMed/NCBI
  28. Sahebkar A, Simental-Mendía LE, Reiner Ž, Kovanen PT, Simental-Mendía M, Bianconi V, et al. Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials. Pharmacol Res 2017;122:53-65 View Article PubMed/NCBI
  29. Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf 2008;31(1):53-65 View Article PubMed/NCBI
  30. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010;363(3):245-256 View Article PubMed/NCBI
  31. Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im K, et al. Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med 2018;379(12):1107-1117 View Article PubMed/NCBI
  32. Sharretts J, Galescu O, Gomatam S, Andraca-Carrera E, Hampp C, Yanoff L. Cancer Risk Associated with Lorcaserin - The FDA’s Review of the CAMELLIA-TIMI 61 Trial. N Engl J Med 2020;383(11):1000-1002 View Article PubMed/NCBI
  33. Pilitsi E, Farr OM, Polyzos SA, Perakakis N, Nolen-Doerr E, Papathanasiou AE, et al. Pharmacotherapy of obesity: Available medications and drugs under investigation. Metabolism 2019;92:170-192 View Article PubMed/NCBI
  34. Cegla J, Troke RC, Jones B, Tharakan G, Kenkre J, McCullough KA, et al. Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake. Diabetes 2014;63(11):3711-3720 View Article PubMed/NCBI
  35. Tan TM, Field BC, McCullough KA, Troke RC, Chambers ES, Salem V, et al. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes 2013;62(4):1131-1138 View Article PubMed/NCBI
  36. Rondanelli M, Miraglia N, Putignano P, Castagliuolo I, Brun P, Dall’Acqua S, et al. Effects of 60-Day Saccharomyces boulardii and Superoxide Dismutase Supplementation on Body Composition, Hunger Sensation, Pro/Antioxidant Ratio, Inflammation and Hormonal Lipo-Metabolic Biomarkers in Obese Adults: A Double-Blind, Placebo-Controlled Trial. Nutrients 2021;13(8):2512 View Article PubMed/NCBI
  37. Golzarand M, Omidian M, Toolabi K. Effect of Garcinia cambogia supplement on obesity indices: A systematic review and dose-response meta-analysis. Complement Ther Med 2020;52:102451 View Article PubMed/NCBI
  38. Benjamin S, Prakasan P, Sreedharan S, Wright AD, Spener F. Pros and cons of CLA consumption: an insight from clinical evidences. Nutr Metab (Lond) 2015;12:4 View Article PubMed/NCBI
  39. Talenezhad N, Mohammadi M, Ramezani-Jolfaie N, Mozaffari-Khosravi H, Salehi-Abargouei A. Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis. Clin Nutr ESPEN 2020;37:9-23 View Article PubMed/NCBI
  40. Johnen H, Lin S, Kuffner T, Brown DA, Tsai VW, Bauskin AR, et al. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat Med 2007;13(11):1333-1340 View Article PubMed/NCBI
  41. Mullican SE, Lin-Schmidt X, Chin CN, Chavez JA, Furman JL, Armstrong AA, et al. GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat Med 2017;23(10):1150-1157 View Article PubMed/NCBI
  42. Grönroos S, Helmiö M, Juuti A, Tiusanen R, Hurme S, Löyttyniemi E, et al. Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss and Quality of Life at 7 Years in Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial. JAMA Surg 2021;156(2):137-146 View Article PubMed/NCBI
  43. Lee G, Park YS, Cho C, Lee H, Park J, Park DJ, et al. Short-term changes in the serum metabolome after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass. Metabolomics 2021;17(8):71 View Article PubMed/NCBI
  44. Padilla N, Maraninchi M, Béliard S, Berthet B, Nogueira JP, Wolff E, et al. Effects of bariatric surgery on hepatic and intestinal lipoprotein particle metabolism in obese, nondiabetic humans. Arterioscler Thromb Vasc Biol 2014;34(10):2330-2337 View Article PubMed/NCBI
  45. Olbers T, Björkman S, Lindroos A, Maleckas A, Lönn L, Sjöström L, et al. Body composition, dietary intake, and energy expenditure after laparoscopic Roux-en-Y gastric bypass and laparoscopic vertical banded gastroplasty: a randomized clinical trial. Ann Surg 2006;244(5):715-722 View Article PubMed/NCBI
  46. Abu Dayyeh BK, Acosta A, Camilleri M, Mundi MS, Rajan E, Topazian MD, et al. Endoscopic Sleeve Gastroplasty Alters Gastric Physiology and Induces Loss of Body Weight in Obese Individuals. Clin Gastroenterol Hepatol 2017;15(1):37-43.e1 View Article PubMed/NCBI
  47. Thompson CC, Abu Dayyeh BK, Kushner R, Sullivan S, Schorr AB, Amaro A, et al. Percutaneous Gastrostomy Device for the Treatment of Class II and Class III Obesity: Results of a Randomized Controlled Trial. Am J Gastroenterol 2017;112(3):447-457 View Article PubMed/NCBI
  48. López-Nava G, Bautista-Castaño I, Jimenez A, de Grado T, Fernandez-Corbelle JP. The Primary Obesity Surgery Endolumenal (POSE) procedure: one-year patient weight loss and safety outcomes. Surg Obes Relat Dis 2015;11(4):861-865 View Article PubMed/NCBI
  49. Sandler BJ, Rumbaut R, Swain CP, Torres G, Morales L, Gonzales L, et al. One-year human experience with a novel endoluminal, endoscopic gastric bypass sleeve for morbid obesity. Surg Endosc 2015;29(11):3298-3303 View Article PubMed/NCBI
  50. Shah R, Davitkov P, Abu Dayyeh BK, Saumoy M, Murad MH. AGA Technical Review on Intragastric Balloons in the Management of Obesity. Gastroenterology 2021;160(5):1811-1830 View Article PubMed/NCBI
  51. Muniraj T, Day LW, Teigen LM, Ho EY, Sultan S, Davitkov P, et al. AGA Clinical Practice Guidelines on Intragastric Balloons in the Management of Obesity. Gastroenterology 2021;160(5):1799-1808 View Article PubMed/NCBI
  52. Crea N, Pata G, Della Casa D, Minelli L, Maifredi G, Di Betta E, et al. Improvement of metabolic syndrome following intragastric balloon: 1 year follow-up analysis. Obes Surg 2009;19(8):1084-1088 View Article PubMed/NCBI
  53. Genco A, López-Nava G, Wahlen C, Maselli R, Cipriano M, Sanchez MM, et al. Multi-centre European experience with intragastric balloon in overweight populations: 13 years of experience. Obes Surg 2013;23(4):515-521 View Article PubMed/NCBI
  54. Vilarrasa N, de Gordejuela AG, Casajoana A, Duran X, Toro S, Espinet E, et al. Endobarrier® in Grade I Obese Patients with Long-Standing Type 2 Diabetes: Role of Gastrointestinal Hormones in Glucose Metabolism. Obes Surg 2017;27(3):569-577 View Article PubMed/NCBI
  55. Ruban A, Miras AD, Glaysher MA, Goldstone AP, Prechtl CG, Johnson N, et al. Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial. Ann Surg 2022;275(3):440-447 View Article PubMed/NCBI
  56. Garvey WT. Ablation of the Duodenal Mucosa as a Strategy for Glycemic Control in Type 2 Diabetes: Role of Nutrient Signaling or Simple Weight Loss. Diabetes Care 2016;39(12):2108-2110 View Article PubMed/NCBI
  • Journal of Translational Gastroenterology
  • eISSN 2994-8754
Back to Top

Obesity and Current Treatment Approaches: A Comprehensive Review

Karthik Mathialagan, Madhumitha Rondla, Karthik Muralidharan, Sun-Joo Jang
  • Reset Zoom
  • Download TIFF