Camilleri, Michael

Objective Endoscopic sleeve gastroplasty (ESG) has gained global adoption but our understanding of its mechanism(s) of action and durability of efficacy is limited. We sought to determine changes in gastric emptying (GE), gastric motility (GM), hormones and eating behaviours after ESG. Design A priori-designed single-centre substudy of a large US randomised clinical trial, adults with obesity were randomised to ESG or lifestyle interventions (LS) alone. We measured GE, hormones and weight loss and assessed eating behaviours. In a subset of ESG patients, we assessed GM. The primary outcome was the change in T1/2 (min) at 3 months, and secondary outcomes were changes in weight, GE, GM, hormones and eating behaviours. We used t-test analyses and regression to determine the association between GE and weight loss. Results 36 (ESG=18; LS=18) participated in this substudy. Baseline characteristics were similar between the two groups. At 3 months, T1/2 was delayed in the ESG group (n=17) compared with the LS group (n=17) (152.3±47.3 vs 89.1±27.9; p<0.001). At 12 months, T1/2 remained delayed in the ESG group (n=16) vs control group (n=14) (137±37.4 vs 90.1±23.4; p<0.001). Greater delays in GE at 3 months were associated with greater weight loss. GM was preserved and fasting ghrelin, glucagon-like peptide 1 and polypeptide YY significantly increased 18 months after ESG. Conclusion ESG promotes weight loss through several key mechanistic pathways involving GE and hormones while preserving GM. These findings further support clinical adoption of this technique for the management of obesity. Trial registration number NCT03406975.

Abstract Aim To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once‐daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity. Methods One hundred and thirty‐six obese adults (87% female) were randomized in a placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET 1/2 ); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET 1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model. Results Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide‐ and 16% of placebo‐treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET 1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4‐kg weight loss were GET 1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57‐3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602‐0.864) per 100 kcal. Among only the 60 liraglutide‐treated subjects, kcal intake at 16 weeks was associated with 4‐kg weight loss (AUROC = 0.757). Conclusions Slower GET 1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide‐treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.

Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

Abstract Objective This study aimed to determine the effects of a long‐acting glucagon‐like peptide‐1 (GLP‐1) receptor agonist, liraglutide, and placebo subcutaneously over 16 weeks on weight and gastric functions and to evaluate associations of single‐nucleotide polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) with effects of liraglutide. Methods The study conducted a randomized, parallel‐group, placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg subcutaneously daily in 136 otherwise healthy adults with obesity. Weight, gastric emptying of solids (GES), gastric volumes, satiation, and body composition measured at baseline and after treatment were compared in two treatment groups using analysis of covariance. Results Liraglutide ( n = 59) and placebo ( n = 65) groups completed treatment. Relative to placebo, liraglutide increased weight loss at 5 and 16 weeks (both p < 0.05), slowed time to half GES (T 1/2 ) at 5 and 16 weeks (both p < 0.001), and increased fasting gastric volume ( p = 0.01) and satiation ( p < 0.01) at 16 weeks. GES T 1/2 was positively correlated with weight loss on liraglutide (both p < 0.001). After 16 weeks of liraglutide, GLP1R rs6923761 (AG/AA vs. GG) was associated with reduced percent body fat ( p = 0.062), and TCF7L2 rs7903146 (CC vs. CT/TT) was associated with lower body weight ( p = 0.015). Conclusions Liraglutide, 3 mg, induces weight loss with delay in GES T 1/2 and reduces calorie intake. Slowing GES and variations in GLP1R and TCF7L2 are associated with liraglutide effects in obesity.

Current selection of different treatments for patients with gastroparesis is empiric or based on trial and error, though pyloric distensibility and diameter may predict response to pyloric interventions. High-resolution antropyloroduodenal manometry (HR-ADM) can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions in patients with suspected gastroparesis. HR-ADM shows promise to provide guidance for selection and individualization of treatments such as prokinetic agents or pyloric interventions for patients with gastroparesis based on documented pathophysiology.

LINKED CONTENTThis article is linked to Khanna et al papers. To view these articles, visit https://doi.org/10.1111/apt.17065