60-month follow-up of Long Limb vs. Standard Limb Roux-en-Y gastric bypass for type 2 diabetes and obesity: the LONG LIMB RCT
Authors: Ansari Saleem , Kamocka Anna , Mazaheri Tina , Ilesanmi Ibiyemi , Jimenez-Pacheco Lara , Alexiadou Kleopatra , Tan Joanna , Chahal Harvinder , Moorthy Krishna , Purkayastha Sanjay , Umpleby Anne Margot , Bloom Stephen Robert , Rubino Francesco , Miras Alexander Dimitri , Ahmed Ahmed Rashid , Tan Tricia 
Published: January 2025

Background
Roux-en-Y gastric bypass is an established treatment option for type 2 diabetes and obesity. However, the optimal lengths for the small intestinal limbs remain controversial with variation in practice. A longer biliopancreatic limb length of 150 cm (‘Long Limb’) was hypothesised to better improve glycaemia compared to the standard Roux-en-Y gastric bypass with a biliopancreatic limb of 50 cm (‘Standard Limb’). The aim of the trial was to evaluate the short-term mechanistic outcomes and the long-term clinical outcomes and safety of Long Limb versus Standard Limb Roux-en-Y gastric bypass.

Methods
We undertook a prospective double-blinded randomised controlled parallel group clinical trial across two sites in London. Participants were randomly assigned (1 : 1) to Long Limb or Standard Limb Roux-en-Y gastric bypass with a fixed alimentary limb of 100 cm. Mixed-meal tolerance tests and a hyperinsulinaemic-euglycaemic clamp were used to measure postprandial gut hormone response, glucose tolerance and insulin sensitivity. The primary outcome for the mechanistic study was the secretion of active glucagon-like peptide-1 at 2 weeks after intervention. Secondary outcomes were insulin sensitivity and fasting/postprandial glucose and insulin concentrations. Clinical outcomes, including HbA1c, number of glucose-lowering medications, weight loss, blood pressure and low-density lipoprotein cholesterol, and adverse events, were collected up to 60 months postoperatively to assess the durability of postoperative weight and glycaemic improvements.

Results
Of the 53 participants randomised, 48 completed the 12-month mechanistic investigation (Standard Limb 24, Long Limb 24) and 38 completed the 60-month follow-up (Standard Limb 18, Long Limb 20). The 24- to 60-month extension study coincided with two waves of the COVID-19 pandemic. There was no difference between the Standard Limb and Long Limb groups for postprandial active glucagon-like peptide-1 secretion (70 ± 32 pmol/L vs. 70 ± 19 pmol/L, respectively; p = 0.43), hepatic insulin sensitivity (3.4 ± 0.9 µmol/kg/min vs. 3.4 ± 1.4 µmol/kg/min, respectively; p = 0.94) and peripheral insulin sensitivity (29.0 ± 9.1 µmol/kg/min vs. 29.2 ± 9.9 µmol/kg/min, respectively; p = 0.98) at 2 weeks post intervention. There was no difference between the Standard Limb and Long Limb groups at 60-month follow-up for glycaemic remission (33% vs. 45%, respectively; p = 0.52), percentage total weight loss (27 ± 9% vs. 26 ± 8%, respectively; p = 0.34), systolic blood pressure (127 ± 11 mmHg vs. 125 ± 14 mmHg, respectively; p = 0.63) and low-density lipoprotein cholesterol (2.0 ± 1.0 mmol/L vs. 2.4 ± 1.0 mmol/L, respectively; p = 0.27).

Conclusion
In conclusion, this study has demonstrated the substantial clinical benefit of Roux-en-Y gastric bypass to people living with type 2 diabetes and obesity; however, this trial did not demonstrate a clinical rationale for the elongation of the biliopancreatic limb of Roux-en-Y gastric bypass to 150 cm to enhance metabolic outcomes for type 2 diabetes and obesity.

Limitations
Although the surgical procedures were designed according to United Kingdom clinical practice at the time of study inception, there is substantial variation in practice internationally. Our original investigation was powered for mechanistic outcomes and is not powered to detect differences in clinical outcomes. Lastly, the loss of participants to follow-up may have limited our statistical power to detect significant differences in the clinical outcomes. We therefore cannot derive definitive conclusions on the relative clinical efficacy of the two variants of Roux-en-Y gastric bypass.

Funding
This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme as award number NIHR130639.