Aims: EndoBarrier is a 60 cm proximal intestinal liner, endoscopically implanted for up to 1 year, designed to mimic the bypass aspect of Roux-en-Y gastric bypass surgery. We aimed to assess its safety and efficacy in patients with advanced diabesity.Methods: Since October 2014 we have implanted 62 Endo-Barriers in our NHS service. By November 2018 all were explanted. Outcomes were monitored in a registry.Results: In 61 of the 62 patients (98.4%) (age 51.4±7.2 years, 54.1% male, 57.4% Europid, diabetes duration 12.0 (8.0–19.5) years, 57.4% insulin-treated, BMI 41.9±7.4 kg/m2) with implant and explant data, mean±SD HbA1c fell by 23.7±21.4 mmol/mol from 80.2±22.5 to 56.5±11.5 mmol/mol (p<0.001), weight fell by 15.9±8.5 kg from 122.6±27.9 to 106.7±28.9 kg (p<0.001), systolic blood pressure from 138.5±15.0 to 125.8±14.6 mmHg (p<0.001), cholesterol from 4.7±1.4 to 3.9±0.9 mmol/L (p<0.001) and alanine aminotransferase (a marker for non-alcoholic fatty liver disease) from 33.2±19.8 to 19.5±11.4 U/L (p<0.001). In the 35 insulin-treated patients, median (IQR) insulin dose reduced from 100 (54–140) to 40 (0–70) units (p<0.001), with 10/35 (28.6%) discontinuing insulin. There were significant falls (UKPDS Risk Engine v2) in the risk of coronary heart disease (CHD) and stroke, suggesting that EndoBarrier treatment in 100 such patients could prevent 8 events of CHD or stroke and save 6 lives over the 10 years. Ten of the 62 patients (16%) required early removal (4 for gastrointestinal haemorrhage, 2 for liver abscess, 1 for another intra-abdominal abscess and 3 for gastrointestinal symptoms). All made a full recovery following device removal and most derived benefit despite early removal.Conclusion: EndoBarrier was highly effective in this setting in patients with advanced diabetes and obesity. Given the high cardiovascular and microvascular risk of these patients, benefits might outweigh risks. As an endoscopic procedure it is relatively simple and non-invasive. Early removal rates require monitoring and there needs to be increased focus on preventing complications but, on balance, EndoBarrier deserves further investigation as a potential treatment for wider use.

IMPORTANCEOveractivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.ObjectiveTo determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.DESIGN, SETTING, AND PARTICIPANTSIn an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).INTERVENTIONSPatients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.MAIN OUTCOMES AND MEASURESThe primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.RESULTSOn February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).CONCLUSIONS AND RELEVANCEIn this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02735707

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Aims: EndoBarrier is a 60 cm duodenal–jejunal bypass liner endoscopically implanted for up to one year. It mimics the bypass part of Roux-en-Y bariatric surgery and reduces weight and HbA1c while it is in situ. We aimed to assess the extent to which these improvements are sustained in people with diabetes in the year following removal.Methods: Between October 2014 and November 2017 we implanted 62 EndoBarriers in an NHS service with all removed by November 2018. Outcomes were monitored in a registry.Results: By November 2019, 46/62 (72%) (mean±SD age 51.5±7.7 years, 52% male, 54.3% white ethnicity, median (IQR) diabetes duration 14.5 (8–20) years, 67.4% insulin-treated and mean±SD body mass index (BMI) 41.6±7.1 kg/m2) had attended and 16/62 (28%) did not attend their one-year post-EndoBarrier follow-up appointment. In those who attended, during EndoBarrier implantation mean±SD HbA1c fell by 21.1±19.6 mmol/mol from 77.1±20.0 to 56.0±11.2 mmol/mol (p<0.001) (by 1.9±1.8% from 9.2±1.8% to 7.3±1.0% (p<0.001)), weight fell by 17.2±8.8 kg from 121.9±29.4 kg to 104.7±30.1 kg (p<0.001), BMI fell from 41.6±7.5 to 35.5±7.5 kg/m2 (p<0.001), systolic blood pressure from 139.0±14.0 to 126.0±14.6 mmHg (p<0.001) and serum alanine aminotransferase from 30.0±16.9 to 18.8±11.0 U/L (p<0.001). Median (IQR) total daily insulin dose reduced from 104 (54–162) to 30 (0–62) units (n=31, p<0.001); 10/31 (32%) insulin-treated people with diabetes were able to discontinue insulin. One year post-EndoBarrier, 18/46 (39%) demonstrated fully sustained improvement, 18/46 (39%) partially sustained improvement and 10/46 (22%) reverted to baseline. Of those deteriorating, 9/10 (90%) had depression and/or bereavement; they also had less fall in weight and HbA1c during EndoBarrier treatment. In the 16/62 (28%) who did not attend follow-up, reasons for non-attendance were too far to travel (25%), need to take time off work (6.3%), severe depression (6.3%) and death (6.3%). In 56.3% of cases no reason was given.Conclusion: Our data demonstrate that EndoBarrier is highly effective in people with long-standing poorly controlled type 2 diabetes and obesity, with maintenance of significant improvement one year after removal in 78% of cases for whom data were available. As an endoscopic procedure it is relatively simple and non-invasive and it deserves further investigation.

Background and aims: EndoBarrier is a 60cm duodenal-jejunal bypass liner endoscopically implanted for up to one year and designed to mimic the bypass part of roux-en-Y bariatric surgery. There is uncertainty concerning the extent to which improvements associated with EndoBarrier treatment are sus-tained once the liner has been removed. We aimed therefore to establish an EndoBarrier service for refractory diabesity and to continue to monitor the people with diabetes after EndoBarrier removal. Methods: Between October 2014 and November 2017, we implanted 62 EndoBarriers in our NHS service. All had been removed by November 2018. Outcomes were monitored in a registry. Results: As of November 2021, all patients reached three years after EndoBarrier removal and of these 43/62 (69%) (mean±SD age 51.6 ± 7.6 years, 55.8% male, 55.8% white ethnicity, median [IQR] diabetes duration 14.6 [8 – 21] years, 62.8% insulin-treated, mean±SD BMI 41.7±7.3 kg/m2) attended follow-up. In those who attended, during EndoBarrier implantation mean±SD HbA1c fell by 20.6±19.6 mmol/mol from 76.3±19.2 to 55.7±11.1 mmol/mol (p<0.001) (by 1.9±1.8% from 9.1±1.8% to 7.2±1.0% [p<0.001]), weight fell by 17.4±9.1 kg from 123.3±30.0 kg to 105.9±30.8 kg (p<0.001), BMI fell from 41.7±7.3 to 35.6±7.7 kg/m2 (p<0.001), systolic blood pressure from 138.7±14.4 to 125.4±14.7 mmHg (p<0.001), cholesterol from 4.6±1.0 to 3.7±0.7mmol/L (p<0.001), and serum alanine aminotransferase from 30.8±17.2 to 19.3±11.2 U/L (p<0.001). In those taking insulin median (IQR) total daily insulin dose reduced from 114 (54–180) to 20 (0–65) units (n=27, p<0.001); 10/27 (37%) insulin-treated people were able to discontinue insulin. Three years after EndoBarrier removal 33/43 (77%) maintained most of the improvement achieved with EndoBarrier whilst 10/43(23%) reverted to baseline. Of those deteriorating 9/10(90%) had depression and/or bereavement and/or major health problems/disability. 10/62(16%) required early Endo-Barrier removal for adverse events or symptoms; all 10 fully recovered after removal and most derived significant benefit. Conclusions: Our data demonstrate that EndoBarrier is highly effective in people with refractory diabesity, with mainte-nance of significant improvement three years after removal in 77% of cases.