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Weight regain and insufficient weight loss are essential problems after metabolic bariatric surgery (MBS) in people living with obesity. Changes in the level of glucagon-like peptide-1 (GLP-1) secreted from the gut after bariatric surgery are one of the underlying mechanisms for successful initial weight loss. Studies and meta-analyses have revealed that postprandial GLP-1 levels increase after the Roux-en-Y gastric bypass and sleeve gastrectomy, but fasting GLP-1 levels do not increase significantly. Some observational studies have shown the relationship between higher postprandial GLP-1 levels and successful weight loss after bariatric surgery. There is growing evidence that GLP-1-receptor agonist (GLP-1-RA) use in patients who regained weight after bariatric surgery has resulted in significant weight loss. In this review, we aimed to summarize the changes in endogenous GLP-1 levels and their association with weight loss after MBS, describe the effects of GLP-1-RA use on weight loss after MBS, and emphasize metabolic adaptations in light of the recent literature. We hypothesized that maintaining higher basal-bolus GLP-1-RA levels may be a promising treatment choice in people with obesity who failed to lose weight after bariatric surgery.

Key Points Obesity continues to be a major public health problem worldwide Bariatric surgery is an effective treatment for severe obesity that results in the improvement or remission of many obesity-related comorbid conditions, as well as sustained weight loss and improvement in quality of life The four most common bariatric operations performed worldwide are laparoscopic sleeve gastrectomy, laparoscopic Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding and duodenal switch Bariatric surgery is now safe, with mortality comparable to common elective general surgical operations Level 1 evidence show that bariatric surgery provides superior short-term and long-term weight loss and improvement of type 2 diabetes mellitus compared with conventional medical therapy Newly approved laparoscopic and endoscopic devices are now available for management of patients with obesity; however, the long-term efficacy of these devices is unknown Obesity is a major public health problem worldwide, and bariatric surgery offers an effective option for treatment of obesity and related comorbidities. Here, Nguyen and Varela discuss the indications, safety and outcomes of different bariatric operations in obesity and related metabolic disorders, such as type 2 diabetes mellitus, and examine emerging surgical treatment options. Obesity is one of the most important public health conditions worldwide. Bariatric surgery for severe obesity is an effective treatment that results in the improvement and remission of many obesity-related comorbidities, as well as providing sustained weight loss and improvement in quality of life. Contemporary bariatric operations include Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric band and the duodenal switch. The vast majority of these procedures are now performed using laparoscopic technique, the main advantages of which include rapid recovery, the reduction of postoperative pain and the reduction of wound-related complications, compared with open surgery. Contemporary bariatric surgery is now safe, with a mortality of three in 1,000 patients; however, all bariatric operations are associated with their own unique short-term and long-term nutritional and procedural-related complications. Type 2 diabetes mellitus (T2DM) is the most studied metabolic disorder associated with obesity, with data demonstrating that improvement and remission of T2DM in patients with obesity is superior after bariatric surgery compared with conventional medical therapy. Bariatric surgery is now a part of some treatment algorithms for the medical management of patients with T2DM and severe obesity. New, minimally invasive and endoscopic devices for the treatment of obesity have now been approved in the USA, which will expand the treatment options for individuals with obesity.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.

Key Points Bariatric surgery has a proven role in achieving sustained weight loss, improving obesity-related comorbidities and reducing mortality Bariatric surgery is considered to address mainly weight loss, whereas metabolic surgery focuses mainly on improving type 2 diabetes mellitus Bariatric and metabolic surgery cannot be viewed as dichotomic procedures, as most of the clinical benefits of both approaches have a multifactorial origin derived from a combination of effects Detailed patient phenotyping shows that the BMI cut-off points for determining eligibility for surgery are blurred when considering total adiposity and fat distribution, as BMI often does not tally with these factors Changes in eligibility and follow-up criteria that move away from a merely BMI-centric view for indicating bariatric or metabolic surgery should be pursued A more functional, individualized and holistic approach with extensive evaluation of comorbidities will yield improved patient selection that does not have a 'weight-centric' focus Bariatric and metabolic surgeries are increasingly being used to treat patients with obesity, which is a major public health challenge. In this Review, Gema Frühbeck discusses the current body of evidence related to the outcomes of bariatric and metabolic surgery. Frühbeck suggests that a paradigm shift in eligibility and success criteria is required. She proposes that patient selection and follow-up should no longer focus solely on weight and BMI. The obesity epidemic, combined with the lack of available and effective treatments for morbid obesity, is a scientific and public health priority. Worldwide, bariatric and metabolic surgeries are increasingly being performed to effectively aid weight loss in patients with severe obesity, as well as because of the favourable metabolic effects of the procedures. The positive effects of bariatric surgery, especially with respect to improvements in type 2 diabetes mellitus, have expanded the eligibility criteria for metabolic surgery to patients with diabetes mellitus and a BMI of 30–35 kg/m 2 . However, the limitations of BMI, both in the diagnosis and follow-up of patients, need to be considered, particularly for determining the actual adiposity and fat distribution of the patients following weight loss. Understanding the characteristics shared by bariatric and metabolic surgeries, as well as their differential aspects and outcomes, is required to enhance patient benefits and operative achievements. For a holistic approach that focuses on the multifactorial effects of bariatric and metabolic surgery to be possible, a paradigm shift that goes beyond the pure semantics is needed. Such a shift could lead to profound clinical implications for eligibility criteria and the definition of success of the surgical approach.

Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin (‘pigment’) stones. Black pigment stones can be caused by chronic haemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and overnutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for ∼25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general. Gallstones are masses in the gallbladder or biliary tract. This Primer by Lammert et al . focuses on the formation of gallstones, summarizes the current principles of treatment of the stones and their potential complications and envisions future approaches for this widespread disease.

Key Points Under normal conditions the intestinal microbiota provide resistance to pathogens The physiological stress of surgical injury on the gastrointestinal tract can result in a profound shift in gut microbiota abundance, function and spatial location Postsurgical re-establishment of the intestinal microbiota population is poorly understood Selective pressures due to the process of surgical care can promote the development of resistant pathogens Major intestinal reconstruction alters the intestinal microbiota; the altered microbiota might contribute to some of the benefits of these procedures, but could also contribute to the development of postsurgical complications The effects of surgical injury can, in some cases, result in an in vivo transformation of intestinal bacteria to a more virulent phenotype Gastrointestinal surgery induces physiological stress and can include major reconstruction of the gastrointestinal tract, which can have profound effects on resident gut microbiota. Here, Guyton and Alverdy describe how the gut microbiota influence recovery after gastrointestinal surgery, including complications such as infection and anastomotic leak. Surgery involving the gastrointestinal tract continues to prove challenging because of the persistence of unpredictable complications such as anastomotic leakage and life-threatening infections. Removal of diseased intestinal segments results in substantial catabolic stress and might require complex reconstructive surgery to maintain the functional continuity of the intestinal tract. As gastrointestinal surgery necessarily involves a breach of an epithelial barrier colonized by microorganisms, preoperative intestinal antisepsis is used to reduce infection-related complications. The current approach to intestinal antisepsis varies widely across institutions and countries with little understanding of its mechanism of action, effect on the gut microbiota and overall efficacy. Many of the current approaches to intestinal antisepsis before gastrointestinal surgery run counter to emerging concepts of intestinal microbiota contributing to immune function and recovery from injury. Here, we review evidence outlining the role of gut microbiota in recovery from gastrointestinal surgery, particularly in the development of infections and anastomotic leak. To make surgery safer and further reduce complications, a molecular, genetic and functional understanding of the response of the gastrointestinal tract to alterations in its microbiota is needed. Methods can then be developed to preserve the health-promoting functions of the microbiota while at the same time suppressing their harmful effects.

The increased prevalence of adolescent obesity and associated short-term and long-term complications emphasize the need for effective treatment. In this Review, we aim to describe the evidence for, and elements of, behaviour management and adjunctive therapies and highlight the opportunities and challenges presented by obesity management in adolescence. The broad principles of treatment include management of obesity-associated complications; a developmentally appropriate approach; long-term behaviour modification (dietary change, increased physical activity, decreased sedentary behaviours and improved sleep patterns); long-term weight maintenance strategies; and consideration of the use of pharmacotherapy, more intensive dietary therapies and bariatric surgery. Bariatric surgery should be considered in those with severe obesity and be undertaken by skilled bariatric surgeons affiliated with teams experienced in the medical and psychosocial management of adolescents. Adolescent obesity management strategies are more reliant on active participation than those for childhood obesity and should recognize the emerging autonomy of the patient. The challenges in adolescent obesity relate primarily to the often competing demands of developing autonomy and not yet having attained neurocognitive maturity.

Bariatric surgery is an effective treatment for obesity, providing long-term maintenance of weight loss. Here, the authors discuss the various mechanisms by which the different types of bariatric surgery (including Roux-en-Y gastric bypass, vertical sleeve gastrectomy and adjusted gastric banding) exert their effects on body weight. Evidence from animal and human studies will be discussed. The clinical efficacy of bariatric surgery has encouraged the scientific investigation of the gut as a major endocrine organ. Manipulation of gastrointestinal anatomy through surgery has been shown to profoundly affect the physiological and metabolic processes that control body weight and glycaemia. The most popular bariatric surgical procedures are gastric bypass, adjustable gastric banding and vertical sleeve gastrectomy. Even though these procedures were designed with the aim of causing restriction of food intake and nutrient malabsorption, evidence suggests that their contributions to weight loss are minimal. Instead, these interventions reduce body weight by decreasing hunger, increasing satiation during a meal, changing food preferences and energy expenditure. In this Review, we have explored these mechanisms as well as their mediators. The hope is that that their in-depth investigation will enable the optimization and individualization of surgical techniques, the development of equally effective but safer nonsurgical weight-loss interventions, and even the understanding of the pathophysiology of obesity itself. Key Points Bariatric surgery is the most effective treatment for weight loss and its long-term maintenance; the most commonly performed procedures are laparoscopic gastric bypass, adjustable gastric banding and vertical sleeve gastrectomy Bariatric surgery improves obesity-related comorbidities and reduces overall and cardiovascular mortality Gastric bypass works by reducing hunger, increasing satiation, changing food preferences and increasing diet-induced energy expenditure Adjustable gastric banding works probably through the reduction in hunger, which might be mediated through vagal signalling Some of the clinical and physiological effects of vertical sleeve gastrectomy are similar to gastric bypass Understanding the mechanisms of action of these procedures could accelerate their optimization and the development of novel, and hopefully safer, medications for obesity and type 2 diabetes mellitus

Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB. Gastric bypass surgery is one of the most effective interventions to achieve durable weight loss. Here, Flynn et al . show that, in mice, bile diversion to the small intestine results in beneficial and sustained metabolic improvements similar to Roux-en-Y gastric bypass surgery.

Background Evidence on the long-term (≥10 years) development of health-related quality of life (HRQoL) following bariatric surgery is still limited and mainly based on small-scale studies. This study aimed to investigate (1) 15-year changes in mental, physical, social, and obesity-related HRQoL after bariatric surgery and non-surgical obesity treatment; and (2) whether sociodemographic factors and pre-operative health status are associated with 15-year HRQoL changes in the surgery group. Methods Participants were from the non-randomized, prospective, controlled Swedish Obese Subjects study. The surgery group ( N  = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls ( N  = 2040) received usual obesity care. Recruitment took place in 1987–2001 and measurements (including six HRQoL scales) were administered before treatment and after 0.5, 1, 2, 3, 4, 6, 8, 10 and 15 years. Multilevel mixed-effect regression models using all observations for estimation were conducted. Results Surgical patients experienced greater 15-year improvements in perceived health and overall mood, and greater reductions in depression, obesity-related problems, and social interaction limitations than controls (all p  < 0.001, adjusted for baseline differences). Effect size (ES) was classified as large only for obesity-related problems (ES = 0.82). At the 15-year follow-up, surgical patients reported better perceived health ( p  < 0.001) and less obesity-related problems ( p  = 0.020) than controls. In the surgery group, patients with baseline diabetes had smaller 15-year reductions in social interaction limitations ( p  < 0.001) and depression ( p  = 0.049) compared to those without baseline diabetes. Although surgical patients with a history of psychiatric disorder reported lower HRQoL than those without such history over the 15-year follow-up, there were no significant differences in the long-term improvements between the two groups ( p  = 0.211–0.902). Conclusions Over 15 years, surgical patients experienced more positive development of HRQoL compared to those receiving usual care. This difference was large for obesity-related problems, but otherwise the differences were small. Patients with pre-operative diabetes might be at increased risk for smaller long-term HRQoL improvements.