Gastric bypass surgery (GB) is highly effective for obesity and type 2 diabetes but is inaccessible to many due to cost and safety concerns. Non-surgical methods mimicking GB's weight-loss mechanisms could broaden access to its benefits. GB's benefits stem from activating multiple systemic and central pathways, a key mechanism being the rapid delivery of nutrients directly to the jejunum. This pilot study aimed to evaluate the effect of repeated rapid nutrient delivery to the jejunum on body weight in ambulatory adults with obesity and type 2 diabetes. Prior research suggests that rapid nutrient delivery to the jejunum stimulates appetite-suppressing gut hormones, alters nutrient sensing, and promotes a fed physiological state, reducing food intake. Several studies have used enteral feeding tubes to investigate nutrient delivery and appetite regulation; however, most have evaluated single doses or short durations. This study hypothesized that repeated jejunal nutrient boluses would promote weight loss and aimed to assess the safety and feasibility of a novel modified enteral feeding tube device allowing for self-administration and continuation of normal daily activities.

The introduction section extensively reviews the literature on bariatric surgery's effectiveness for obesity and type 2 diabetes, highlighting its limitations due to cost and safety concerns. It cites studies demonstrating the mechanisms of weight loss following GB surgery, emphasizing the role of rapid nutrient delivery to the jejunum and the subsequent release of appetite-suppressing hormones. The review also includes previous research on enteral feeding tubes, their use in studying nutrient effects on appetite, and the limitations of prior studies in terms of single-dose administration or short durations. This sets the stage for the current study's rationale and hypothesis.

This study employed a randomized, crossover pilot trial design. Initially planned as a parallel-group trial, it was modified due to slow enrollment to a crossover design. Sixteen participants with obesity and type 2 diabetes were randomized 1:1 to receive either a mixed-meal (MM) or electrolyte solution (ES) bolus via a novel orojejunal tube four times daily for 14 days. After a 14-day washout period, participants crossed over to the other treatment arm. A custom-made intraoral anchor secured the 8-French feeding tube. Participants were instructed to maintain their usual dietary habits. The primary outcome measure was 14-day weight change. Secondary outcomes included 28-day weight change and weight change during the post-intervention 14-day period. Participants were encouraged to continue their usual activities and were monitored weekly for safety and efficacy. The mixed meal consisted of Ensure Nutrition Shake, and the electrolyte solution was unflavored Pedialyte. Insulin and other diabetic medications were adjusted as clinically indicated. Body weight was measured weekly using a calibrated scale. Statistical analysis involved a general linear model comparing treatments for the primary outcome, with adjustments for crossover sequence and cycle number. A paired t-test was used for comparing baseline and final measures in participants completing at least two cycles.

Ten participants withdrew before completing both treatment cycles due to social reasons, intolerance to the anchor, or intolerance to the tube. The primary analysis of the six participants who completed both cycles showed no significant difference in weight loss between MM and ES (p=0.082). However, the secondary analysis revealed a significant within-group weight loss for the MM group (-2.40 kg, p=0.008) but not for the ES group (-0.64 kg, p=0.27). A total of 23 two-week cycles were completed (12 paired, 2 unpaired, and 9 additional), representing 334 days of tube use. No significant adverse events were reported. An exploratory analysis including additional MM cycles further supported the finding of significant weight loss with MM compared to ES.

This pilot study demonstrated the feasibility of repeated bolus nutrient administration via a novel orojejunal tube in ambulatory adults with obesity and type 2 diabetes. While there was no significant difference between MM and ES in the primary analysis, the secondary analysis showed significant weight loss in the MM group. This suggests that repeated bolus feeding to the jejunum may be associated with weight loss. The low feasibility of the current technique highlights the need for device improvements. The study's limitations include a small sample size, high dropout rate, lack of blinding, and potential bias in medication adjustments. However, the absence of significant adverse events over a considerable duration of tube use suggests that the approach is safe and warrants further investigation. The observed weight loss without dietary restriction suggests potential mechanisms beyond simple caloric restriction. The results support further research using an improved device and protocol, incorporating measures of food intake, gut hormones, appetite, and gut transit to elucidate the mechanisms of weight loss.

This pilot study demonstrated the feasibility of repeated bolus jejunal nutrient administration using a novel intraorally anchored enteral feeding tube. While the current device requires further development to improve tolerance and recruitment, the observed weight loss in the mixed meal group suggests potential for this approach in weight management. Future studies should focus on device refinement, larger sample sizes, blinding, and more comprehensive data collection to fully elucidate the mechanisms and efficacy of this intervention.

The study's limitations include a small sample size (only six participants completed both treatment cycles), high dropout rate, lack of blinding, and the potential for bias introduced by the investigator's adjustments of medications. The position of the tube tip was not consistently confirmed, and adherence to the treatment protocol was not formally assessed. These limitations affect the generalizability and interpretation of the findings and highlight the need for further, more rigorous research.